Sujana S. Chandrasekhar
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Τετάρτη 26 Ιουλίου 2017
Benefit of Radiotherapy After Breast Conservation in DCIS
Can this molecular assay help determine who will benefit from radiotherapy after breast-conserving therapy for DCIS?
Journal of the National Cancer Institute
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Journal of the National Cancer Institute
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Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators
Future Oncology, Ahead of Print.
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Th9 cells induce steroid-resistant bronchial hyperresponsiveness in mice
Publication date: Available online 26 July 2017
Source:Allergology International
Author(s): Mayumi Saeki, Osamu Kaminuma, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BackgroundReduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice.MethodsOvalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4+ T cells of DO11.10/RAG-2−/− mice. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Dex treatment was performed twice, at 1 h before and at 24 h after the OVA challenge. Following treatment, the number of inflammatory cells in the bronchoalveolar lavage fluid and the bronchial responsiveness to inhaled methacholine were determined.ResultsIn both the Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with the specific antigen. In the Th2 cell-transferred mice, these responses were significantly diminished by Dex treatment. In contrast, neither cellular infiltration nor BHR was affected by Dex treatment in the Th9 cell-transferred mice, although the Th9 cells substantially expressed glucocorticoid receptor α. Accordingly, antigen-induced interleukin-9 expression in the Th9 cells was attenuated by Dex treatment at least in vitro. Antigen-induced lung infiltration of infused Th2 cells but not Th9 cells was significantly suppressed by Dex.ConclusionsIn contrast to Th2-mediated responses, Th9-mediated airway inflammation was not affected by Dex. Th9 cells might be involved in the developmental mechanisms of steroid-resistant asthma.
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Source:Allergology International
Author(s): Mayumi Saeki, Osamu Kaminuma, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BackgroundReduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice.MethodsOvalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4+ T cells of DO11.10/RAG-2−/− mice. BALB/c mice were adoptively transferred with Th2 or Th9 cells and challenged with OVA. Dex treatment was performed twice, at 1 h before and at 24 h after the OVA challenge. Following treatment, the number of inflammatory cells in the bronchoalveolar lavage fluid and the bronchial responsiveness to inhaled methacholine were determined.ResultsIn both the Th2 and Th9 cell-transferred mice, substantial accumulation of eosinophils in the lungs and BHR were induced by challenge with the specific antigen. In the Th2 cell-transferred mice, these responses were significantly diminished by Dex treatment. In contrast, neither cellular infiltration nor BHR was affected by Dex treatment in the Th9 cell-transferred mice, although the Th9 cells substantially expressed glucocorticoid receptor α. Accordingly, antigen-induced interleukin-9 expression in the Th9 cells was attenuated by Dex treatment at least in vitro. Antigen-induced lung infiltration of infused Th2 cells but not Th9 cells was significantly suppressed by Dex.ConclusionsIn contrast to Th2-mediated responses, Th9-mediated airway inflammation was not affected by Dex. Th9 cells might be involved in the developmental mechanisms of steroid-resistant asthma.
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The effect of active components from citrus fruits on dentin MMPs
Source:Archives of Oral Biology, Volume 83
Author(s): Zhengya Liu, Fang Li, Ling Zhang, Haohan Yu, Fan Yu, Jihua Chen
ObjectivesThis study was aimed to evaluate the anti-matrix metalloproteinases (MMPs) ability of active components from citrus fruits (hesperetin: Hst, hesperidin: Hsd and naringenin: Nge).MethodsInactivation effects of citrus flavonoids (Hst, Hsd, Nge) at different concentrations on soluble collagenase were measured using a fluorometric assay. Matrix-bound endogenous MMPs activity was evaluated via dry mass loss and hydroxyproline (HYP) release of demineralized human dentin. Demineralized dentin beams were pretreated with 500μg/mL citrus flavonoids for 10min. Chlorhexidine (CHX) was used as inhibitor control. Beams pretreated with distilled water served as blank control. Dentin slabs were used for in situ zymography and evaluated under confocal microscopy. Ultrastructure of demineralized collagen fibers was exhibited by Transmission Electron Microscopy (TEM).ResultsCitrus flavonoids exhibited inactivation function on soluble MMPs and the extent of inactivation increased in a dose-dependent manner. The inactivation percent of citrus flavonoids reached above 90% at the concentration of 500μg/mL. Compared with control group, citrus flavonoids pretreated demineralized dentin beams exhibited less dry mass loss, lower hydroxyproline release and more intact collagen architecture after 15days storage. Dentin samples pretreated with citrus flavonoids showed lower enzymes activities in in situ zymography.ConclusionsHst, Hsd or Nge have anti-MMPs ability and can preserve dentin collagen from degradation.Clinical Significance: Hst, Hsd and Nge may have the potential to be used in dentin bonding systems and improve the resin-dentin bonding durability.
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Validation study of a new method for sexual prediction based on CBCT analysis of maxillary sinus and mandibular canal
Source:Archives of Oral Biology, Volume 83
Author(s): Thiago de Oliveira Gamba, Mayra Cristina Yamasaki, Francisco Carlos Groppo, Heraldo Luis Dias da Silveira, Solange Maria de Almeida Boscolo, Gerard C.H. Sanderink, W. Erwin R. Berkhout
ObjectiveThe aim of this study was to evaluate the accuracy of two craniometric methods for sexual prediction (SP) using cone-beam computed tomography (CBCT) in the Dutch population and to construct a formula for each method and then the two combined.DesignOne-hundred sixty CBCT images were selected from a Dutch database (80 males and 80 females). The images were analyzed by two examiners taking seven measurements in the maxillary sinus (MS) region (first method) and nine in the mandibular canal (MC) region (second method). The most predictive measurements in both methods were used to develop an equation to determine the accuracy of each method.ResultsAll measurements showed statistical difference between genders. Logistic regression results showed two variables with greater SP index with 75% accuracy in the first method and four variables with 71.9% accuracy in the second. The two methods combined showed another four variables with 78.5% accuracy.ConclusionAll measurements showed statistically significant differences between sexes. The SP accuracy values were 75% for first 71.9% for the second method. When the two methods were combined, the accuracy increased to 78.5%. The formulas developed in this study can be applied as a complementary method for human identification in the Dutch population.
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Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators
Future Oncology, Ahead of Print.
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“Analysis of the correlation between dental arch and articular eminence morphology: a cone beam CT study”
Publication date: Available online 26 July 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Francielle Silvestre Verner, Gina Delia Roque-Torres, Laura Ricardina Ramírez-Sotello, Karina Lopes Devito, Solange Maria Almeida
Objective.To assess the correlation between the morphology of the dental arches (DA) of patients with normal occlusion and the articular eminence (AE) through cone beam computed tomography (CBCT).Study Design.CBCT scans of 60 patients were evaluated in terms of height (AEh) and inclinations (angles α, β and δ) of the AE. DA were classified regarding shape (tapered, square, ovoid), and perimeters, widths, and depths were measured. One-way ANOVA, Pearson's correlation coefficients, simple and multivariate linear regression models were calculated.Results.Ovoid arch was the most predominant shape (n = 66/120). Inclination of the AE (angle β) had the greatest difference between DA shapes, with this angle usually being greater in the ovoid and smaller in the square arches (p<0.05). The AEh presented greater correlation with DA measurements, with tapered arches having the most significant correlations (p<0.05). DA depth had no influence on AE measurements (p>0.05). Perimeter and width of the DA had some influence (p<0.05).Conclusions.Correlations between DA and AE morphologies of were found. Although the results do not prove absolute association between the variables, the correlations should be taken into consideration. Whenever possible, morphological features of DA should be preserved to avoid possible changes in AE.
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Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Francielle Silvestre Verner, Gina Delia Roque-Torres, Laura Ricardina Ramírez-Sotello, Karina Lopes Devito, Solange Maria Almeida
Objective.To assess the correlation between the morphology of the dental arches (DA) of patients with normal occlusion and the articular eminence (AE) through cone beam computed tomography (CBCT).Study Design.CBCT scans of 60 patients were evaluated in terms of height (AEh) and inclinations (angles α, β and δ) of the AE. DA were classified regarding shape (tapered, square, ovoid), and perimeters, widths, and depths were measured. One-way ANOVA, Pearson's correlation coefficients, simple and multivariate linear regression models were calculated.Results.Ovoid arch was the most predominant shape (n = 66/120). Inclination of the AE (angle β) had the greatest difference between DA shapes, with this angle usually being greater in the ovoid and smaller in the square arches (p<0.05). The AEh presented greater correlation with DA measurements, with tapered arches having the most significant correlations (p<0.05). DA depth had no influence on AE measurements (p>0.05). Perimeter and width of the DA had some influence (p<0.05).Conclusions.Correlations between DA and AE morphologies of were found. Although the results do not prove absolute association between the variables, the correlations should be taken into consideration. Whenever possible, morphological features of DA should be preserved to avoid possible changes in AE.
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Targeted next-generation sequencing of glandular odontogenic cyst: a preliminary study
Publication date: Available online 26 July 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Elisa Carvalho de Siqueira, Silvia Ferreira de Sousa, Josiane Alves França, Marina Gonçalves Diniz, Thaís dos Santos Fontes Pereira, Rennan Garcias Moreira, Pablo Agustin Vargas, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
Background: Glandular odontogenic cyst (GOC) is an uncommon developmental cyst. Its molecular pathogenesis is unclear and deep sequencing technologies may identify causative low-frequency variants in tumors. Objective: We investigated in GOC mutations in 50 genes commonly altered in human cancers Methods: Targeted next-generation sequencing was used to interrogate a panel of approximately 2,800 mutations in GOC. Results: Six missense single nucleotide variations (SNVs) were reported. Three SNVs (TP53 rs1042522, KDR rs1870377 and KIT rs3822214) are listed as “common SNPs” at the UCSC Genome Browser. The other SNVs (PIK3CA p.Glu689Lys, PIK3CA p.Ala708Thr and TP53 p.Leu289Phe) are predicted to have deleterious or damaging effects on the proteins, but they showed very low frequency in our samples and could not be further validated by orthogonal methods. Conclusion: No pathogenic SNV was detected in this cohort of GOC. Further studies with larger gene panels or whole exome sequencing are needed in order to reveal the genetic basis of GOC.
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Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Elisa Carvalho de Siqueira, Silvia Ferreira de Sousa, Josiane Alves França, Marina Gonçalves Diniz, Thaís dos Santos Fontes Pereira, Rennan Garcias Moreira, Pablo Agustin Vargas, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
Background: Glandular odontogenic cyst (GOC) is an uncommon developmental cyst. Its molecular pathogenesis is unclear and deep sequencing technologies may identify causative low-frequency variants in tumors. Objective: We investigated in GOC mutations in 50 genes commonly altered in human cancers Methods: Targeted next-generation sequencing was used to interrogate a panel of approximately 2,800 mutations in GOC. Results: Six missense single nucleotide variations (SNVs) were reported. Three SNVs (TP53 rs1042522, KDR rs1870377 and KIT rs3822214) are listed as “common SNPs” at the UCSC Genome Browser. The other SNVs (PIK3CA p.Glu689Lys, PIK3CA p.Ala708Thr and TP53 p.Leu289Phe) are predicted to have deleterious or damaging effects on the proteins, but they showed very low frequency in our samples and could not be further validated by orthogonal methods. Conclusion: No pathogenic SNV was detected in this cohort of GOC. Further studies with larger gene panels or whole exome sequencing are needed in order to reveal the genetic basis of GOC.
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Functional Independence Measure - Minimum Data Set Motor Item Bank: Short Forms Development and Precision Comparison in Veterans
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chih-Ying Li, Sergio Romero, Annie N. Simpson, Heather S. Bonilha, Kit N. Simpson, Ickpyo Hong, Craig A. Velozo
ObjectiveTo improve the practical use of the short forms (SFs) developed from the item bank, we compared the measurement precision of the 4- and 8-item SFs generated from a motor item bank composed of the Functional Independence Measure (FIM™) and the Minimum Data Set (MDS).DesignThe FIM-MDS motor item bank allowed scores generated from different instruments to be co-calibrated. The 4- and 8-item SFs were developed based on Rasch analysis procedures. This paper compared person strata, ceiling/floor effects, test standard error (SE) plots for each administration form and examined 95% confidence interval (CI) error bands of anchored person measures with the corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level of 0.90.SettingVeterans’ inpatient rehabilitation facilities and community living centers.Participants2500 Veterans who had both FIM and the MDS data within 6 days during years 2008 through 2010.InterventionsNAMain Outcome Measure(s)4- and 8-item SFs of FIM, MDS and FIM-MDS motor item bank.ResultsSix SFs were generated with 4- and 8-items across a range of difficulty levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher correlations with the item bank (r=0.82∼0.95), higher person strata and less test error than the corresponding 4-item SFs (r=0.80∼ 0.90). The three 4-item SFs did not meet the criteria of SE less than 0.3 for any theta values.Conclusions8-item short forms could improve clinical use of item bank composed of existing instruments across the continuum of care in Veterans. We also found number of items, not test specificity, determines the precision of the instrument.
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Do trials of resistance training to improve mobility after stroke adhere to the American College of Sports Medicine guidelines? A systematic review
Publication date: Available online 26 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Genevieve Hendrey, Anne E. Holland, Benjamin F. Mentiplay, Ross Clark, Gavin Williams
ObjectiveTo determine whether resistance training to improve mobility outcomes after stroke adhere to the ACSM guidelines, and whether adherence was associated with better outcomes.Data sourcesOnline databases searched from 1975 to 30 October 2016.Study SelectionRandomized controlled trials examining the effectiveness of lower limb strength training on mobility outcomes in adult stroke participants.Data Extraction and AnalysisTwo independent reviewers completed data extraction. Quality of trials was determined using the Cochrane Risk of Bias Tool. Trials were scored based on their protocol’s adherence to eight ACSM recommendations. To determine if a relationship existed between total adherence score and effect size, Spearman’s rho (rs) was calculated and between individual recommendations and effect size, Mann Whitney U or Kruskal Wallis tests were used.ResultsThirty-nine trials met the inclusion criteria and 34 were scored on their adherence to the guidelines. Adherence was high for frequency of training (100% of studies) but few trials adhered to the guidelines for intensity (32%), specificity (24%), and training pattern (3%). Based on the small number of studies that could be included in pooled analysis (n = 12), there was no relationship between overall adherence and effect size (rs = -0.39, p = 0.21).ConclusionsAdherence to the ACSM guidelines for resistance training following stroke varied widely. Future trials should ensure strength training protocols adhere more closely to the guidelines, to ensure their effectiveness in stroke can be accurately determined.
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Source:Archives of Physical Medicine and Rehabilitation
Author(s): Genevieve Hendrey, Anne E. Holland, Benjamin F. Mentiplay, Ross Clark, Gavin Williams
ObjectiveTo determine whether resistance training to improve mobility outcomes after stroke adhere to the ACSM guidelines, and whether adherence was associated with better outcomes.Data sourcesOnline databases searched from 1975 to 30 October 2016.Study SelectionRandomized controlled trials examining the effectiveness of lower limb strength training on mobility outcomes in adult stroke participants.Data Extraction and AnalysisTwo independent reviewers completed data extraction. Quality of trials was determined using the Cochrane Risk of Bias Tool. Trials were scored based on their protocol’s adherence to eight ACSM recommendations. To determine if a relationship existed between total adherence score and effect size, Spearman’s rho (rs) was calculated and between individual recommendations and effect size, Mann Whitney U or Kruskal Wallis tests were used.ResultsThirty-nine trials met the inclusion criteria and 34 were scored on their adherence to the guidelines. Adherence was high for frequency of training (100% of studies) but few trials adhered to the guidelines for intensity (32%), specificity (24%), and training pattern (3%). Based on the small number of studies that could be included in pooled analysis (n = 12), there was no relationship between overall adherence and effect size (rs = -0.39, p = 0.21).ConclusionsAdherence to the ACSM guidelines for resistance training following stroke varied widely. Future trials should ensure strength training protocols adhere more closely to the guidelines, to ensure their effectiveness in stroke can be accurately determined.
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Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic and periodontal bacterial species?
Source:Dental Materials
Author(s): Suping Wang, Haohao Wang, Biao Ren, Hao Li, Michael D. Weir, Xuedong Zhou, Thomas W. Oates, Lei Cheng, Hockin H.K. Xu
ObjectivesAntibacterial monomers were developed to combat oral biofilm acids and caries; however, little is known on whether quaternary ammonium monomers (QAMs) would induce drug resistance in oral bacteria. The objective of this study was to investigate the effects of new antimicrobial monomers dimethylaminohexadecyl methacrylate (DMAHDM) and dimethylaminododecyl methacrylate (DMADDM) on the induction of drug resistance in eight species of cariogenic, endodontic and periodontal bacteria for the first time.MethodsStreptococcus mutans (S. mutans), Streptococcus sanguis, Streptococcus gordonii, Enterococcus faecalis (E. faecalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), Porphyromonas gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) were tested. Minimum inhibitory concentration (MIC) was assessed using chlorhexidine (CHX) as control. Minimal bactericidal concentration (MBC), bacterial growth and membrane permeability properties were also investigated.ResultsCHX induced drug resistance in four species. DMAHDM did not induce any resistance. DMADDM induced drug resistance in only one benign species S. gordonii. The DMADDM-resistant and CHX-resistant S. gordonii had the same MIC and MBC values as S. gordonii parental strain against DMAHDM (p>0.1), hence DMAHDM effectively inhibited the resistant strains. The resistant strains had slower growth metabolism than parental strain.SignificanceDMAHDM induced no drug resistance, and DMADDM had much less drug resistance than the commonly-used CHX in the eight common oral species. With its potent antimicrobial functions shown previously, the new DMAHDM is promising for applications in restorative, preventive, periodontal and endodontic treatments to combat cariogenic and pathological bacteria with no drug resistance in all tested species.
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Respiratory muscle endurance training reduces the O2 cost of cycling and perceived exertion in obese adolescents.
In obesity the increased O2 cost of breathing negatively affects the O2 cost of exercise and exercise tolerance. The purpose of the study was to determine whether, in obese adolescents, the addition of respiratory muscle endurance training (RMET) (isocapnic hyperpnea) to a standard body mass reduction program decreases the O2 cost of exercise and perceived exertion and increases exercise tolerance. 9 male obese adolescents (16.0±1.4 years [x±SD], body mass 114.4±22.3 kg) underwent 3 weeks of RMET (5 days/week); 8 age-and sex- matched obese adolescents underwent the standard body mass reduction program (CTRL). Before and after interventions patients performed on a cycle ergometer: incremental exercise; 12-min constant work-rate exercises (CWR) at 65% and 120% of gas exchange threshold (GET) determined before the intervention. Breath-by-breath pulmonary ventilation (V'E) and O2 uptake (V'O2), heart rate (HR) and ratings of perceived exertion for dyspnea/respiratory discomfort (RPER) and leg effort (RPEL) were determined. Body mass decreased (by ~3.0 kg) after both RMET and CTRL (P=0.001; GLM for repeated measures). Peak O2 and peak work rate were not affected by both interventions. During CWR<GET no changes were observed after both interventions. During CWR>GET the O2 cost of cycling (P=0.014), the slope of V'O2 vs. time (P=0.012), RPER (P=0.012), RPEL (P=0.016) and HR (P=0.001) decreased following RMET but not following CTRL, whereas V'E did not change. In obese adolescents RMET, superimposed on a standard body mass reduction program, lowered the O2 cost of cycling and perceived exertion during constant heavy-intensity exercise.
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Chronic Hindbrain Administration of Oxytocin is Sufficient to Elicit Weight Loss in Diet-Induced Obese Rats
Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates and humans by both reducing energy intake and increasing energy expenditure (EE). Although the neurocircuitry underlying these effects remains uncertain, OT neurons in the paraventricular nucleus are positioned to control both energy intake and sympathetic nervous system outflow to interscapular brown adipose tissue (IBAT) through projections to both the hindbrain nucleus of the solitary tract and spinal cord. The current work was undertaken to examine whether central OT increases BAT thermogenesis, whether this effect involves hindbrain OT receptors (OTRs), and whether such effects are associated with sustained weight loss following chronic administration. To assess OT-elicited changes in BAT thermogenesis, we measured the effects of intracerebroventricular administration of OT on IBAT temperature (TIBAT) in both rats and mice. Because fourth ventricular (4V) infusion targets hindbrain OTRs, whereas third ventricular (3V) administration targets both forebrain and hindbrain OTRs, we compared responses to OT following chronic 3V infusion in DIO rats and mice with chronic 4V infusion in DIO rats. We report that chronic 4V infusion of OT into two distinct rat models recapitulates the effects of 3V OT to ameliorate diet-induced obesity by reducing fat mass. While reduced food intake contributes to this effect, our finding that 4V OT also increases BAT thermogenesis suggests that increased EE may contribute as well. These findings collectively support the hypothesis that in DIO rats, OT action in the hindbrain evokes sustained weight loss by both reducing energy intake and increasing BAT thermogenesis.
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Spot Urine Protein Measurements in Normotensive Pregnancies, Pregnancies with Isolated Proteinuria and Preeclampsia
We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In normotensive pregnancy (n=142), we found that from the beginning of pregnancy to delivery, UACR increased by a median (interquartile range (IQR)) of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) (p<0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19 /142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery, and increases in UACR from early to mid-pregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early and mid-pregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a 'microalbuminuric' phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared to women with preeclampsia, where proteinuria has a more abrupt onset.
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Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project
Purpose: The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein–Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer.
Experimental Design: Gene expression data from a TCGA cohort (n = 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts (n = 267 and 432). An integrated risk assessment model (TCGA risk score) was also developed.
Results: EBV subtype was associated with the best prognosis, and GS subtype was associated with the worst prognosis. Patients with MSI and CIN subtypes had poorer overall survival than those with EBV subtype but better overall survival than those with GS subtype (P = 0.004 and 0.03 in two cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score was an independent prognostic factor [HR, 1.5; 95% confidence interval (CI), 1.2–1.9; P = 0.001]. Patients with the CIN subtype experienced the greatest benefit from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16–0.94; P = 0.03) and those with the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95% CI, 0.36–1.89; P = 0.65).
Conclusions: Our prediction model successfully stratified patients by survival and adjuvant chemotherapy outcomes. Further development of the prediction model is warranted. Clin Cancer Res; 23(15); 1–9. ©2017 AACR.
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Isoflurane, ketamine-xylazine, and urethane markedly alter breathing even at sub-therapeutic doses
Anesthetics are widely used for animal research on respiratory control in vivo, but their effect on breathing and CO2 chemoreception has not been well characterized in mice, a species now often used for these studies. We previously demonstrated that 1% isoflurane markedly reduces the hypercapnic ventilatory response (HCVR) in adult mice in vivo and masks serotonin (5-hydroxytryptamine; 5-HT) neuron chemosensitivity in vitro. Here we investigated effects of 0.5% isoflurane on breathing in adult mice, and also found a large reduction in the HCVR even at this sub-anesthetic concentration. We then tested the effects on breathing of ketamine-xylazine and urethane - anesthetics widely used in research on breathing. We found that these agents altered baseline breathing and blunted the HCVR at doses within the range typically used experimentally. At lower doses ventilation was decreased, but mice appropriately matched their ventilation to metabolic demands due to a parallel decrease in O2 consumption. Neither ketamine nor urethane decreased chemosensitivity of 5-HT neurons. These results indicate that baseline breathing and/or CO2 chemoreception in mice are decreased by anesthetics widely viewed as not affecting respiratory control, and even at sub-therapeutic doses. These effects of anesthetics on breathing may alter the interpretation of studies of respiratory physiology in vivo.
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Alpha-motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.
Small diameter sensory dysfunction resulting from diabetes has received much attention in the literature, while the impact of diabetes on alpha-motoneurons (MN) has not. In addition to this, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker Diabetic Fatty (ZDF) rats were separated into Lean, Obese (ZDF fed standard chow) and Diabetic (ZDF fed high fat diet that led to diabetes) groups. Glass micropipettes recorded hind-limb motoneuron properties from identified flexor and extensor motoneurons. Motoneurons were separated within their groups based on input conductance, which created high and low input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in low conductance motoneurons for the diabetic group only, while the AHP1/2 tended to be shorter in the Obese group (19%). Significant positive correlations were found among Rheobase and input conductance for both lean and obese animals. No differences were found between the groups for the afterhyperpolarization amplitude (AHPamp), input conductance (IC), rheobase or any of the rhythmic firing properties (Frequency-Current slope and spike frequency adaptation index). Motoneuron properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar motoneurons. Despite the motoneurons resistance to the impact of diabetes, the reduced AHP 1/2 decay and the tendency for a reduction in AHPamp may be the first sign of change to motoneuron function.
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Unbounded evidence accumulation characterizes subjective visual vertical (SVV) forced-choice perceptual choice and confidence
Humans can subjectively yet quantitatively assess choice confidence based on perceptual precision even when a perceptual decision is made without an immediate reward or feedback. However, surprisingly little is known about choice confidence. Here we investigate the dynamics of choice confidence by merging two parallel conceptual frameworks of decision-making, signal detection theory and sequential analyses (i.e., drift diffusion modeling). Specifically, in order to capture end-point statistics of binary choice and confidence, we built on a previous study that defined choice confidence in terms of psychophysics derived from signal detection theory. At the same time, we augmented this mathematical model to include accumulator dynamics of a drift-diffusion model to characterize the time-dependency of the choice behaviors in a standard forced-choice paradigm in which stimulus duration is controlled by the operator. Human subjects performed a subjective visual vertical task, simultaneously reporting binary orientation choice and probabilistic confidence. Both binary choice and confidence experimental data displayed statistics and dynamics consistent with both signal detection theory and evidence accumulation, respectively. Specifically, the computational simulations showed that the unbounded evidence accumulator model fits the confidence data better than the classical bounded model, while bounded and unbounded models were indistinguishable for binary choice data. These results suggest that the brain can utilize mechanisms consistent with signal detection theory - especially when judging confidence without time pressure.
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Sympathetic neural and hemodynamic responses to head-up tilt during iso-osmotic and hyper-osmotic hypovolemia
We hypothesized that muscle sympathetic nerve activity (MSNA) during head-up tilt (HUT) would be augmented during exercise-induced (hyperosmotic) dehydration but not iso-osmotic dehydration via oral diuretic. We studied 26 young healthy subjects (7 F, 19 M) divided into 3 groups: euhydrated (EUH, n = 7), previously exercised in 40°C while maintaining hydration; dehydrated (DEH, n = 10), previously exercised in 40 °C who lost ~3% of body weight via sweat loss; and diuretic (DIUR, n = 9), who did not exercise and lost ~3% of bodyweight via diuresis (furosemide, 80 mg po). We measured MSNA, heart rate (HR), blood pressure (BP) during supine rest and 30° and 45° HUT. Plasma volume (PV) decreased similarly in DEH (-8.5 ± 3.3%) and DIUR (-11.4 ± 5.7%) (p> 0.05). Plasma osmolality was similar between DIUR and EUH (288 ± 4 vs 284 ± 5 mmol/kg, respectively), but was significantly higher in DEH (299 ± 5 mmol/kg) (p<0.05). Mixed-model ANOVA was used with repeated measures on position (HUT) and between-group analysis on condition. HR and MSNA increased in all subjects during HUT. There was a significant main effect of group, such that MSNA and HR were higher in DEH compared to DIUR (P < 0.05). Changes in HR with HUT were larger in both hypovolemic groups compared to EUH (P < 0.05). The differential HUT response "strategies" in each group suggest a greater role for hypovolemia per se in controlling HR responses during dehydration, and a stronger role for osmolality in control of SNA.
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Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in the three-layer turtle cortex
A primary goal of systems neuroscience is to understand cortical function, which typically involves studying spontaneous and stimulus-modulated cortical activity. Mounting evidence suggests a strong and complex relationship exists between the ongoing and stimulus-modulated cortical state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope; it records the activity of a minority of neurons, and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but stable recordings are difficult to obtain in vivo. Here, we recorded subthreshold cortical visual responses in the ex vivo turtle eye-attached whole-brain preparation, which is ideally-suited for such a study. We found that in the absence of visual stimulation, the network was "synchronous"; neurons displayed network-mediated transitions between low- and high-conductance membrane potential states. The prevalence of these slow-wave transitions varied across turtles and recording sessions. Visual stimulation evoked similar high-conductance states, which were on average larger and less reliable when the ongoing state was more synchronous. Responses were muted when immediately preceded by large, spontaneous high-conductance events. Evoked spiking was sparse, highly variable across trials, and mediated by concerted synaptic inputs that were in general only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons.
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Lethal digenic mutations in the K+ channels Kir4.1 (KCNJ10) and SLACK (KCNT1) associated with severe-disabling seizures and neurodevelopmental delay
A 2-year-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia and tonic-clonic seizures that caused the death of the patient. Targeted and whole-exome sequencing revealed two heterozygous missense variants: a novel mutation in KCNJ10 gene that encodes for the inwardly-rectifying K+ channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na+-activated K+ channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4.1 mutation. The mutant and wild-type KCNJ10 constructs were generated and heterologously expressed in Xenopus laevis oocytes, and whole-cell K+ currents were measured using the two-electrode voltage-clamp technique. The KCNJ10 mutation c.652C>T resulted in a p.L218F substitution at a highly conserved residue site. Wild-type KCNJ10 expression yielded robust Kir currents, while currents from oocytes expressing the mutation were reduced. Western Blot analysis revealed reduced protein expression by the mutation. Kir5.1 subunits display selective heteromultimerization with Kir4.1 constituting channels with unique kinetics. The effect of the mutation on Kir4.1/5.1 channel activity was twofold: a reduction in current amplitudes and an increase in the pH-dependent inhibition. We thus report a novel loss-of-function mutation in Kir4.1 found in a patient with a co-exiting mutation in SLACK channels that results in a fatal disease.
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Functional Independence Measure - Minimum Data Set Motor Item Bank: Short Forms Development and Precision Comparison in Veterans
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chih-Ying Li, Sergio Romero, Annie N. Simpson, Heather S. Bonilha, Kit N. Simpson, Ickpyo Hong, Craig A. Velozo
ObjectiveTo improve the practical use of the short forms (SFs) developed from the item bank, we compared the measurement precision of the 4- and 8-item SFs generated from a motor item bank composed of the Functional Independence Measure (FIM™) and the Minimum Data Set (MDS).DesignThe FIM-MDS motor item bank allowed scores generated from different instruments to be co-calibrated. The 4- and 8-item SFs were developed based on Rasch analysis procedures. This paper compared person strata, ceiling/floor effects, test standard error (SE) plots for each administration form and examined 95% confidence interval (CI) error bands of anchored person measures with the corresponding SFs. We used 0.3 SE as a criterion to reflect a reliability level of 0.90.SettingVeterans' inpatient rehabilitation facilities and community living centers.Participants2500 Veterans who had both FIM and the MDS data within 6 days during years 2008 through 2010.InterventionsNAMain Outcome Measure(s)4- and 8-item SFs of FIM, MDS and FIM-MDS motor item bank.ResultsSix SFs were generated with 4- and 8-items across a range of difficulty levels from the FIM-MDS motor item bank. The three 8-item SFs all had higher correlations with the item bank (r=0.82∼0.95), higher person strata and less test error than the corresponding 4-item SFs (r=0.80∼ 0.90). The three 4-item SFs did not meet the criteria of SE less than 0.3 for any theta values.Conclusions8-item short forms could improve clinical use of item bank composed of existing instruments across the continuum of care in Veterans. We also found number of items, not test specificity, determines the precision of the instrument.
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Do trials of resistance training to improve mobility after stroke adhere to the American College of Sports Medicine guidelines? A systematic review
Publication date: Available online 26 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Genevieve Hendrey, Anne E. Holland, Benjamin F. Mentiplay, Ross Clark, Gavin Williams
ObjectiveTo determine whether resistance training to improve mobility outcomes after stroke adhere to the ACSM guidelines, and whether adherence was associated with better outcomes.Data sourcesOnline databases searched from 1975 to 30 October 2016.Study SelectionRandomized controlled trials examining the effectiveness of lower limb strength training on mobility outcomes in adult stroke participants.Data Extraction and AnalysisTwo independent reviewers completed data extraction. Quality of trials was determined using the Cochrane Risk of Bias Tool. Trials were scored based on their protocol's adherence to eight ACSM recommendations. To determine if a relationship existed between total adherence score and effect size, Spearman's rho (rs) was calculated and between individual recommendations and effect size, Mann Whitney U or Kruskal Wallis tests were used.ResultsThirty-nine trials met the inclusion criteria and 34 were scored on their adherence to the guidelines. Adherence was high for frequency of training (100% of studies) but few trials adhered to the guidelines for intensity (32%), specificity (24%), and training pattern (3%). Based on the small number of studies that could be included in pooled analysis (n = 12), there was no relationship between overall adherence and effect size (rs = -0.39, p = 0.21).ConclusionsAdherence to the ACSM guidelines for resistance training following stroke varied widely. Future trials should ensure strength training protocols adhere more closely to the guidelines, to ensure their effectiveness in stroke can be accurately determined.
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THE THIRD STIMULUS TEMPORAL DISCRIMINATION THRESHOLD: FOCUSING ON THE TEMPORAL PROCESSING OF SENSORY INPUT WITHIN PRIMARY SOMATOSENSORY CORTEX
BACKGROUND: The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information but little is known about the physiological correlates of somatosensory temporal discrimination. OBJECTIVE: To investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the Third Stimulus Temporal Discrimination Threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus after a pair of stimuli delivered at the STDT. METHODS: the STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1-continuous theta burst stimulation (cTBS) on the STDT and ThirdDT. RESULTS: ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, though the latter was affected to a greater extent and for a longer period of time. CONCLUSION: The interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1 probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination.
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Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM)
Background: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. Summary: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.
Eur Surg Res 2017;58:246–262
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Eur Surg Res 2017;58:246–262
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Impact of the Korean Diagnosis-Related Groups payment system on the outcomes of adenotonsillectomy: A single center experience
To report outcomes with regard to clinical aspects and medical costs of adenotonsillectomy and tonsillectomy at a single institution before and after implementation of the Diagnosis-Related Groups (DRG) payment system in Korea.
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Surgical considerations and safety of cochlear implantation in otitis media with effusion
To evaluate the effects of otitis media with effusion on surgical parameters, patient safety, perioperative and postoperative complications.
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Endoscopic contralateral transmaxillary approach for pterygoid process osteotomy in total maxillectomy: A technical case report
An approach for total maxillectomy with endoscopic transection of the pterygoid process via the contralateral maxillary sinus is described. In total maxillectomy, the resection of the pterygoid process of the sphenoid is a key step for successful resection. However, a conventional craniofacial approach requires extensive incision in the face, elevation of the lateral cheek flap. Even after elevation of the lateral cheek flap, visualization of this region is not good. An endoscopic approach through the contralateral maxillary sinus improved visualization of the pterygoid process, and osteotomy using a diamond-drilling bar was successfully performed.
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Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential
Pathological high frequency oscillations (pHFOs, 80-500 Hz) recorded in the pre and intra-operative ECoG of epilepsy patients have been proposed as a biomarker for the identification of the epileptogenic zone (Jacobs et al., 2012). Particularly for epilepsy surgery, it has been demonstrated that residual fast ripples (FR, > 250 Hz) are a reliable predictor of seizure outcome (Fedele et al., 2017; van 't Klooster et al., 2015; Wu et al., 2010). While faster oscillations have higher clinical relevance, they suffer from a poor signal-to-noise ratio (SNR).
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Comparative efficacy of various endoscopic techniques for the treatment of common bile duct stones: A network meta-analysis
Although various endoscopic techniques have been introduced for successful removal of common bile duct (CBD) stones, the optimal method is not yet clear. We aimed to compare the efficacy of different endoscopic techniques for CBD stone removal.
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Impact of the Korean Diagnosis-Related Groups payment system on the outcomes of adenotonsillectomy: A single center experience
Source:Auris Nasus Larynx
Author(s): Sang Hyun Kwak, Ji Hoon Kim, Da Hee Kim, Jung Min Kim, Hyung Kwon Byeon, Won Shik Kim, Yoon Woo Koh, Se-Heon Kim, Eun Chang Choi
ObjectivesTo report outcomes with regard to clinical aspects and medical costs of adenotonsillectomy and tonsillectomy at a single institution before and after implementation of the Diagnosis-Related Groups (DRG) payment system in Korea.MethodsWe retrospectively reviewed the records of patients treated with adenotonsillectomy or tonsillectomy between July 2012 and June 2014. The Korean DRG payment system was applied to seven groups of specific diseases and surgeries including adenotonsillectomy and tonsillectomy from July 2013 at all hospitals in Korea. We divided patients into four groups according whether the fee-for-service (FFS) or DRG payment system was implemented and operation type (FFS-adenotonsillectomy (AT), DRG-AT, FFS-tonsillectomy (T), and DRG-T).ResultsA total of 1402 patients were included (485 FFS-AT, 490 DRG-AT, 203 FFS-T, and 223 DRG-T). The total medical cost of the DRG-AT group was significantly lower than that of the FFS-AT group (1191±404 vs. 1110±279 USD, P<0.05). There were no significant differences in length of hospital stay or postoperative complications among groups.ConclusionThe Korean DRG system for adenotonsillectomy and tonsillectomy reduced medical costs and clinical outcomes were not significantly altered by the adoption of the DRG system.Level of evidence4.
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The association of mothers’ and fathers’ insomnia symptoms with school-aged children’s sleep assessed by parent report and in-home sleep-electroencephalography
Sleep plays an essential role for children’s well-being. Because children’s sleep is associated with parental sleep patterns, it must be considered in the family context. As a first aim of the present study, we test whether parental insomnia symptoms are related to children’s in-home sleep-electroencephalography (EEG). Second, we examine the association between parental insomnia symptoms and maternal and paternal perception of children’s sleep using actor–partner interdependence models.
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What predicts inattention in adolescents? An experience-sampling study comparing chronotype, subjective and objective sleep parameters
Many adolescents sleep insufficiently, which may negatively affect their functioning during the day. To improve sleep interventions, we need a better understanding of the specific sleep-related parameters that predict poor functioning. We investigated to which extent subjective and objective parameters of sleep in the preceding night (state parameters) and the trait variable chronotype predict daytime inattention as an indicator of poor functioning.
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Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort
Pregnancy and the obesity epidemic impacting women of reproductive age appear to predispose women to obstructive sleep apnea (OSA) in pregnancy. The aim of this study is to examine the association between OSA and adverse maternal outcomes in a national cohort.
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Isoflurane, ketamine-xylazine, and urethane markedly alter breathing even at sub-therapeutic doses
Anesthetics are widely used for animal research on respiratory control in vivo, but their effect on breathing and CO2 chemoreception has not been well characterized in mice, a species now often used for these studies. We previously demonstrated that 1% isoflurane markedly reduces the hypercapnic ventilatory response (HCVR) in adult mice in vivo and masks serotonin (5-hydroxytryptamine; 5-HT) neuron chemosensitivity in vitro. Here we investigated effects of 0.5% isoflurane on breathing in adult mice, and also found a large reduction in the HCVR even at this sub-anesthetic concentration. We then tested the effects on breathing of ketamine-xylazine and urethane - anesthetics widely used in research on breathing. We found that these agents altered baseline breathing and blunted the HCVR at doses within the range typically used experimentally. At lower doses ventilation was decreased, but mice appropriately matched their ventilation to metabolic demands due to a parallel decrease in O2 consumption. Neither ketamine nor urethane decreased chemosensitivity of 5-HT neurons. These results indicate that baseline breathing and/or CO2 chemoreception in mice are decreased by anesthetics widely viewed as not affecting respiratory control, and even at sub-therapeutic doses. These effects of anesthetics on breathing may alter the interpretation of studies of respiratory physiology in vivo.
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Alpha-motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.
Small diameter sensory dysfunction resulting from diabetes has received much attention in the literature, while the impact of diabetes on alpha-motoneurons (MN) has not. In addition to this, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker Diabetic Fatty (ZDF) rats were separated into Lean, Obese (ZDF fed standard chow) and Diabetic (ZDF fed high fat diet that led to diabetes) groups. Glass micropipettes recorded hind-limb motoneuron properties from identified flexor and extensor motoneurons. Motoneurons were separated within their groups based on input conductance, which created high and low input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in low conductance motoneurons for the diabetic group only, while the AHP1/2 tended to be shorter in the Obese group (19%). Significant positive correlations were found among Rheobase and input conductance for both lean and obese animals. No differences were found between the groups for the afterhyperpolarization amplitude (AHPamp), input conductance (IC), rheobase or any of the rhythmic firing properties (Frequency-Current slope and spike frequency adaptation index). Motoneuron properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar motoneurons. Despite the motoneurons resistance to the impact of diabetes, the reduced AHP 1/2 decay and the tendency for a reduction in AHPamp may be the first sign of change to motoneuron function.
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Unbounded evidence accumulation characterizes subjective visual vertical (SVV) forced-choice perceptual choice and confidence
Humans can subjectively yet quantitatively assess choice confidence based on perceptual precision even when a perceptual decision is made without an immediate reward or feedback. However, surprisingly little is known about choice confidence. Here we investigate the dynamics of choice confidence by merging two parallel conceptual frameworks of decision-making, signal detection theory and sequential analyses (i.e., drift diffusion modeling). Specifically, in order to capture end-point statistics of binary choice and confidence, we built on a previous study that defined choice confidence in terms of psychophysics derived from signal detection theory. At the same time, we augmented this mathematical model to include accumulator dynamics of a drift-diffusion model to characterize the time-dependency of the choice behaviors in a standard forced-choice paradigm in which stimulus duration is controlled by the operator. Human subjects performed a subjective visual vertical task, simultaneously reporting binary orientation choice and probabilistic confidence. Both binary choice and confidence experimental data displayed statistics and dynamics consistent with both signal detection theory and evidence accumulation, respectively. Specifically, the computational simulations showed that the unbounded evidence accumulator model fits the confidence data better than the classical bounded model, while bounded and unbounded models were indistinguishable for binary choice data. These results suggest that the brain can utilize mechanisms consistent with signal detection theory - especially when judging confidence without time pressure.
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Sympathetic neural and hemodynamic responses to head-up tilt during iso-osmotic and hyper-osmotic hypovolemia
We hypothesized that muscle sympathetic nerve activity (MSNA) during head-up tilt (HUT) would be augmented during exercise-induced (hyperosmotic) dehydration but not iso-osmotic dehydration via oral diuretic. We studied 26 young healthy subjects (7 F, 19 M) divided into 3 groups: euhydrated (EUH, n = 7), previously exercised in 40°C while maintaining hydration; dehydrated (DEH, n = 10), previously exercised in 40 °C who lost ~3% of body weight via sweat loss; and diuretic (DIUR, n = 9), who did not exercise and lost ~3% of bodyweight via diuresis (furosemide, 80 mg po). We measured MSNA, heart rate (HR), blood pressure (BP) during supine rest and 30° and 45° HUT. Plasma volume (PV) decreased similarly in DEH (-8.5 ± 3.3%) and DIUR (-11.4 ± 5.7%) (p> 0.05). Plasma osmolality was similar between DIUR and EUH (288 ± 4 vs 284 ± 5 mmol/kg, respectively), but was significantly higher in DEH (299 ± 5 mmol/kg) (p<0.05). Mixed-model ANOVA was used with repeated measures on position (HUT) and between-group analysis on condition. HR and MSNA increased in all subjects during HUT. There was a significant main effect of group, such that MSNA and HR were higher in DEH compared to DIUR (P < 0.05). Changes in HR with HUT were larger in both hypovolemic groups compared to EUH (P < 0.05). The differential HUT response "strategies" in each group suggest a greater role for hypovolemia per se in controlling HR responses during dehydration, and a stronger role for osmolality in control of SNA.
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Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in the three-layer turtle cortex
A primary goal of systems neuroscience is to understand cortical function, which typically involves studying spontaneous and stimulus-modulated cortical activity. Mounting evidence suggests a strong and complex relationship exists between the ongoing and stimulus-modulated cortical state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope; it records the activity of a minority of neurons, and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but stable recordings are difficult to obtain in vivo. Here, we recorded subthreshold cortical visual responses in the ex vivo turtle eye-attached whole-brain preparation, which is ideally-suited for such a study. We found that in the absence of visual stimulation, the network was "synchronous"; neurons displayed network-mediated transitions between low- and high-conductance membrane potential states. The prevalence of these slow-wave transitions varied across turtles and recording sessions. Visual stimulation evoked similar high-conductance states, which were on average larger and less reliable when the ongoing state was more synchronous. Responses were muted when immediately preceded by large, spontaneous high-conductance events. Evoked spiking was sparse, highly variable across trials, and mediated by concerted synaptic inputs that were in general only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons.
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Lethal digenic mutations in the K+ channels Kir4.1 (KCNJ10) and SLACK (KCNT1) associated with severe-disabling seizures and neurodevelopmental delay
A 2-year-old boy presented profound developmental delay, failure to thrive, ataxia, hypotonia and tonic-clonic seizures that caused the death of the patient. Targeted and whole-exome sequencing revealed two heterozygous missense variants: a novel mutation in KCNJ10 gene that encodes for the inwardly-rectifying K+ channel Kir4.1 and another previously characterized mutation in KCNT1 that encodes for the Na+-activated K+ channel known as Slo2.2 or SLACK. The objectives of this study were to perform the clinical and genetic characterization of the proband and his family and to examine the functional consequence of the Kir4.1 mutation. The mutant and wild-type KCNJ10 constructs were generated and heterologously expressed in Xenopus laevis oocytes, and whole-cell K+ currents were measured using the two-electrode voltage-clamp technique. The KCNJ10 mutation c.652C>T resulted in a p.L218F substitution at a highly conserved residue site. Wild-type KCNJ10 expression yielded robust Kir currents, while currents from oocytes expressing the mutation were reduced. Western Blot analysis revealed reduced protein expression by the mutation. Kir5.1 subunits display selective heteromultimerization with Kir4.1 constituting channels with unique kinetics. The effect of the mutation on Kir4.1/5.1 channel activity was twofold: a reduction in current amplitudes and an increase in the pH-dependent inhibition. We thus report a novel loss-of-function mutation in Kir4.1 found in a patient with a co-exiting mutation in SLACK channels that results in a fatal disease.
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THE THIRD STIMULUS TEMPORAL DISCRIMINATION THRESHOLD: FOCUSING ON THE TEMPORAL PROCESSING OF SENSORY INPUT WITHIN PRIMARY SOMATOSENSORY CORTEX
BACKGROUND: The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information but little is known about the physiological correlates of somatosensory temporal discrimination. OBJECTIVE: To investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the Third Stimulus Temporal Discrimination Threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus after a pair of stimuli delivered at the STDT. METHODS: the STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1-continuous theta burst stimulation (cTBS) on the STDT and ThirdDT. RESULTS: ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, though the latter was affected to a greater extent and for a longer period of time. CONCLUSION: The interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1 probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination.
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Cardiopulmonary Exercise Testing in Adult Congenital Heart Disease
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S93-S101, July 2017.
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Exercise Testing, Supplemental Oxygen, and Hypoxia
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S140-S148, July 2017.
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Cardiopulmonary Exercise Testing
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Measuring Cardiac Output during Cardiopulmonary Exercise Testing
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S48-S52, July 2017.
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Cardiopulmonary Exercise Testing in Patients with Heart Failure with Specific Comorbidities
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S110-S115, July 2017.
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Cardiopulmonary Exercise Testing in Pulmonary Hypertension
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S84-S92, July 2017.
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Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential
Pathological high frequency oscillations (pHFOs, 80-500 Hz) recorded in the pre and intra-operative ECoG of epilepsy patients have been proposed as a biomarker for the identification of the epileptogenic zone (Jacobs et al., 2012). Particularly for epilepsy surgery, it has been demonstrated that residual fast ripples (FR, > 250 Hz) are a reliable predictor of seizure outcome (Fedele et al., 2017; van 't Klooster et al., 2015; Wu et al., 2010). While faster oscillations have higher clinical relevance, they suffer from a poor signal-to-noise ratio (SNR).
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Exercise Prescriptions for Training and Rehabilitation in Patients with Heart and Lung Disease
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S59-S66, July 2017.
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Graphical Data Display for Clinical Cardiopulmonary Exercise Testing
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S12-S21, July 2017.
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Ventilatory Inefficiency and Exertional Dyspnea in Early Chronic Obstructive Pulmonary Disease
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S22-S29, July 2017.
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Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S3-S11, July 2017.
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FABP1 and Hepar expression levels in Barrett's Oesophagus and Associated Neoplasia in an Asian Population
Barrett's oesophagus (BE) is a premalignant condition associated with oesophageal adenocarcinoma (EAC). Evidence highlights that EAC is associated with an estimated 5-year survival of approximately 10-15%. Therefore, there is a need to determine which biomarkers are of value in the diagnosis of BE and beyond. The aim of our study was to evaluate the clinical significance of markers known to be expressed across BE and associated neoplasia.
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Both positive and negative beliefs are important in patients with spine pain: findings from the oioc registry
Negative beliefs are known to influence treatment outcome in patients with spine pain (SP). The impact of positive beliefs is less clear.
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Effectiveness of psychological interventions delivered by non-psychologists on low back pain and disability: a qualitative systematic review.
Psychological treatments delivered by non-psychologists have been proposed as a way to increase access to care to address important psychological barriers to recovery in people with low back pain (LBP).
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Is the size and composition of the paraspinal muscles associated with low back pain? A systematic review
Background ContextAlthough previous studies have investigated the association between paraspinal muscle morphology and low back pain (LBP), the results are conflicting.PurposeThis systematic review examined the relationship between size and composition of the paraspinal muscles and LBP.Study design/ setting: Systematic reviewPatient sample: N/AOutcome measures: N/AMethodsA systematic search of electronic databases was conducted to identify studies investigating the association between the cross-sectional area and/or fatty infiltration of the paraspinal muscles (erector spinae, multifidus, psoas and quadratus lumborum) and LBP.
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Obesity and spinal epidural lipomatosis in cauda equina syndrome
Although lumbar disc herniations are common, only a small portion of these herniations lead to cauda equina syndrome (CES) which is an uncommon but debilitating disorder. Why some patients with herniation develop CES, when most do not, remains unknown. Pre-existing subclinical epidural lipomatosis may limit canal space such that an otherwise benign herniation causes CES.
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The Link between Reduced Inspiratory Capacity and Exercise Intolerance in Chronic Obstructive Pulmonary Disease
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S30-S39, July 2017.
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Cardiopulmonary Exercise Testing and Metabolic Myopathies
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S129-S139, July 2017.
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Prognostic Role of Cardiopulmonary Exercise Testing in Clinical Practice
Annals of the American Thoracic Society, Volume 14, Issue Supplement_1, Page S53-S58, July 2017.
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Paediatric Dermatofibrosarcoma Protuberans (DFSP): Evaluation of a Rare Childhood Malignancy, the Welsh Experience
A letter to author regarding paediatric DFSP.
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Surgery and Adjuvant Radiation for High-risk Skin Adnexal Carcinoma of the Head and Neck
Objectives: Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that arises from sebaceous and sweat glands. These carcinomas are believed to behave more aggressively than cutaneous squamous cell carcinomas (SCC) with a propensity for local recurrence. The role of adjuvant radiotherapy in SAC is undefined. Methods: We retrospectively reviewed all cases of head and neck SAC treated with surgery and adjuvant radiation from 2000 to 2012 at a single institution. Results: Nine cases were identified. Median age was 67 (range, 52 to 88) years. The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1), skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to confirm the SAC diagnosis. All patients had undergone surgery. Indications for adjuvant radiation included involved lymph nodes (n=4), perineural invasion (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5). Radiation was delivered to the primary site alone (n=3), to the draining lymphatics alone (n=2), or to both (n=4). One patient received concurrent cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50 Gy. Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3 toxicity and no greater than or equal to grade 2 late toxicities were recorded. Conclusions: Surgery and adjuvant radiation for high-risk SAC offers excellent locoregional control with acceptable toxicity.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1GiZg
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FABP1 and Hepar expression levels in Barrett's Oesophagus and Associated Neoplasia in an Asian Population
Barrett's oesophagus (BE) is a premalignant condition associated with oesophageal adenocarcinoma (EAC). Evidence highlights that EAC is associated with an estimated 5-year survival of approximately 10-15%. Therefore, there is a need to determine which biomarkers are of value in the diagnosis of BE and beyond. The aim of our study was to evaluate the clinical significance of markers known to be expressed across BE and associated neoplasia.
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Stage I Lung SBRT Clinical Practice Patterns
Objectives: Stereotactic body radiation therapy (SBRT) has become increasingly utilized over the last decade in the treatment of inoperable stage I non–small cell lung cancer (NSCLC) patients, although no standardized dosing guidelines exist. In this retrospective study, we investigated the dose prescription pattern use in the United States for patients receiving SBRT. Methods: Patients with stage I NSCLC treated with SBRT between 2004 and 2011 were identified within the National Cancer Database (NCDB). Trends in SBRT use and dose prescriptions were analyzed. Results: A total of 5246 patients met criteria as receiving SBRT. The overall mean and median BED10 were 134.5 and 132 Gy, respectively. Of these patients, 94.5% were prescribed a regimen with a BED10≥100 Gy. The most common prescriptions overall were 60 Gy in 3 fractions (24.1%), 48 Gy in 4 fractions (17.8%), 50 Gy in 5 fractions (13.0%), and 54 Gy in 3 fractions (12.8%). Analysis of prescription trends revealed decreased utilization of 54 to 60 Gy in 3 fractions (47.9% in 2006 to 27.9% in 2011, combined) and increased utilization of 50 Gy in 5 fractions (3.1% in 2006 to 20.4% in 2011). Conclusions: Our findings suggest increasing use of SBRT over the last decade with a majority of patients being treated with regimens employing a BED10≥100 Gy. Since 2006, there has been a decline in the use of 54 to 60 Gy in 3 fractions, with an increase in the use of 50 Gy in 5 fractions. Possible explanations include concern for increased toxicity with higher BED regimens and increasing treatment of centrally located tumors.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1ld12
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Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal
Purpose: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. Materials and Methods: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. Results: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. Conclusions: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1Ahvr
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The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor: A Meta-analysis of 25 RCTs
Objective: To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non–small cell lung cancer (NSCLC) patients with wild-type (WT) EGFR tumors, we performed an indirect meta-analysis to assess the treatment effects of EGFR-TKIs in such patients. Methods: We searched for randomized controlled trials in Medline, Embase, the Cochrane controlled trials register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Effect measures used were hazard ratios (HR) for progression-free survival (PFS) and overall survival. Results: Out of 2134 retrieved articles, 25 randomized controlled trials including more than 4467 patients were identified. This pooled analysis showed the inferior efficacy of TKI over chemotherapy among patients with WT EGFR NSCLC in terms of PFS (HR, 1.37; 95% confidence interval [CI]: 1.10, 1.72; P=0.006). When used as first-line treatment, TKIs have also fared worse than chemotherapy when compared with standard platinum doublet regimens in patients with WT EGFR in terms of PFS (HR, 2.15; 95% CI: 1.68, 2.76; Pfrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1iN2n
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Contemporary Patterns and Survival Outcome of Adjuvant Systemic Therapy for Localized Gastrointestinal Stromal Tumors
Objectives: To describe contemporary patterns of and factors associated with adjuvant therapy use and survival outcome after resection of localized gastrointestinal stromal tumors (GISTs) using a large contemporary clinical database. Methods: We queried the National Cancer Data Base to identify localized GIST cases diagnosed from 2004 to 2011, and used descriptive and logistic regression analyses to determine patterns of and factors associated with adjuvant therapy. Kaplan-Meier and Cox proportional-hazard model were utilized to generate survival probabilities and hazard ratios (HRs). Results: Of 4694 patients, 73.5% received surgery alone, and 26.5% received adjuvant therapy during 2004 to 2011. Receipt of adjuvant therapy more than doubled between 2006 (13.2%) and 2007 (30.5%), peaked to 37.9% in 2009, and then decreased to 25.6% in 2011 (P for trend10 cm) than those with smaller tumor size (≤5 cm) (44.1% vs. 15.8%; P10 cm tumor size (HR=0.42; 95% confidence interval, 0.20-0.89; P=0.02). Conclusions: In a large nationwide dataset, we showed that the use of adjuvant therapy for localized GISTs has significantly increased over time and patients treated with adjuvant therapy have better survival than patients treated with surgery alone.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1fkkj
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Influence of NSAID Use Among Colorectal Cancer Survivors on Cancer Outcomes
Purpose: Colorectal cancer (CRC) is the third most common cancer diagnosed in men and women in the United States. Given the availability of effective screening, most tumors are found early enough to offer patients substantial long-term survival. Thus there is a resulting significant population of CRC survivors for whom modifiable risk factors for recurrence and survival would be of interest. Methods: We conducted a population-based retrospective cohort study among patients enrolled in 2 large Midwestern health plans for which claims data, including pharmacy fill data, and medical record data were available. Men and women who were 40 years of age or older at the time of CRC diagnosis with disease less than stage IV and no history of Crohn disease, ulcerative colitis, and irritable bowel syndrome were included. CRC cases diagnosed between January 1, 1990 and December 31, 2000 were included if they met the inclusion criteria. Adjusted Cox proportional hazard models were used with exposure modeled as a time-dependent covariate. We assessed progression-free survival, defined as an aggressive polyp or invasive disease, and overall survival. Results: After adjustment for age at diagnosis, sex, race, body mass index, stage, side of initial tumor, and tumor histology, we found that current users of nonsteroidal anti-inflammatory drugs had a 3-fold decreased risk of recurrence and a >7-fold decreased risk of death. Our results are statistically significant with P-valuesfrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2w1qIN8
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Pathway discovery using transcriptomic profiles in adult-onset severe asthma
Publication date: Available online 26 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand De Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene. Lutter, ArunaT. Bansal, Ana R. Sousa, Steve. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie. Corfield, Peter. Howarth, Elisabeth H. Bel, Ian M. Adcock, K.F. Chung, Ratko Djukanovic, Peter J. Sterk
RationaleAdult-onset severe asthma is characterized by highly symptomatic disease despite high intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease needed for the development of targeted treatments. Gene Set Variation Analysis (GSVA) is a statistical technique to identify gene profiles in heterogeneous samples.ObjectiveTo identify gene profiles associated with adult-onset severe asthma.MethodsThis was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at ≥18yrs old) as compared to childhood-onset severe asthma (<18 yrs) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n=83), nasal brushings (n=41), and endobronchial brushings (n=65) and biopsies (n=47) (Affymetrix HT HG-U133+ PM). GSVA was used to identify differentially enriched pre-defined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.ResultsSignificant differentially enriched gene signatures in patients with adult-onset as compared to childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures) and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells and group 3 innate lymphoid cells (ILC3) were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.ConclusionsAdult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells and ILC3s. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
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Source:Journal of Allergy and Clinical Immunology
Author(s): Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand De Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene. Lutter, ArunaT. Bansal, Ana R. Sousa, Steve. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie. Corfield, Peter. Howarth, Elisabeth H. Bel, Ian M. Adcock, K.F. Chung, Ratko Djukanovic, Peter J. Sterk
RationaleAdult-onset severe asthma is characterized by highly symptomatic disease despite high intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease needed for the development of targeted treatments. Gene Set Variation Analysis (GSVA) is a statistical technique to identify gene profiles in heterogeneous samples.ObjectiveTo identify gene profiles associated with adult-onset severe asthma.MethodsThis was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at ≥18yrs old) as compared to childhood-onset severe asthma (<18 yrs) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n=83), nasal brushings (n=41), and endobronchial brushings (n=65) and biopsies (n=47) (Affymetrix HT HG-U133+ PM). GSVA was used to identify differentially enriched pre-defined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.ResultsSignificant differentially enriched gene signatures in patients with adult-onset as compared to childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures) and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells and group 3 innate lymphoid cells (ILC3) were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.ConclusionsAdult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells and ILC3s. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
Graphical abstract
Teaser
This study elucidates distinct gene profiles in adult-onset severe asthma compared to childhood-onset severe asthma. Identified gene profiles include those associated with eosinophils, ILC3s and mast cells, and may represent targets for new treatments.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uDgGSQ
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Liver disease predicts mortality in patients with XHIM but can be prevented by early hematopoietic stem cell transplantation
Source:Journal of Allergy and Clinical Immunology
Author(s): Vian Azzu, Lucinda Kennard, Beatriz Morillo-Gutierrez, Mary Slatter, J.David M. Edgar, Dinakantha S. Kumararatne, William JH. Griffiths
Teaser
In the largest detailed study of liver disease in X-linked immunodeficiency with hyper-IgM, we show that liver disease is commoner than generally recognized and that early hematopoietic stem cell transplantation may prevent liver disease progression and improve survival.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uD4H7X
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Prevalence of clinic-defined food allergy in early adolescence: The SchoolNuts study
Publication date: Available online 26 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Mari Sasaki, Jennifer J. Koplin, Shyamali C. Dharmage, Michael J. Field, Susan M. Sawyer, Vicki McWilliam, Rachel L. Peters, Lyle C. Gurrin, Peter J. Vuillermin, Jo Douglass, Angela Pezic, Maia Brewerton, Mimi L.K. Tang, George C. Patton, Katrina J. Allen
BackgroundRising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC).ObjectiveWe sought to determine the prevalence of food allergy among a population-based sample of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis.MethodsSchools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only.ResultsThe prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common.ConclusionsApproximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.
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Source:Journal of Allergy and Clinical Immunology
Author(s): Mari Sasaki, Jennifer J. Koplin, Shyamali C. Dharmage, Michael J. Field, Susan M. Sawyer, Vicki McWilliam, Rachel L. Peters, Lyle C. Gurrin, Peter J. Vuillermin, Jo Douglass, Angela Pezic, Maia Brewerton, Mimi L.K. Tang, George C. Patton, Katrina J. Allen
BackgroundRising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC).ObjectiveWe sought to determine the prevalence of food allergy among a population-based sample of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis.MethodsSchools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only.ResultsThe prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common.ConclusionsApproximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.
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A partially hydrolyzed 100% whey formula and the risk of eczema and any allergy: an updated meta-analysis
Recently, the role of using hydrolyzed formula for the prevention of allergic disease has been questioned. However, not all hydrolyzed formulas are equal. The efficacy of each hydrolyzed formula should be esta...
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Paediatric Dermatofibrosarcoma Protuberans (DFSP): Evaluation of a Rare Childhood Malignancy, the Welsh Experience
Publication date: Available online 26 July 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Alexandra Gordon, Jonathan J. Cubitt, Nicholas Wilson-Jones
A letter to author regarding paediatric DFSP.
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Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Alexandra Gordon, Jonathan J. Cubitt, Nicholas Wilson-Jones
A letter to author regarding paediatric DFSP.
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High-dose-rate brachytherapy boost for prostate cancer: Comparison of three different fractionation schemes
Source:Brachytherapy
Author(s): Alexander T. Falk, Sylvain Demontoy, Emmanuel Chamorey, Marie-Eve Chand, Mathieu Gautier, David Azria, Sara Zaki, Daniel Chevallier, Daniel Lam Cham Kee, Jean-Michel Hannoun-Lévi
PurposeDose escalation for prostate cancer can be achieved with a combination of external beam radiotherapy (EBRT) and brachytherapy (BT) boost to increase local control. For high-dose-rate (HDR)-BT, optimal fractionation remains under debate. The objective was to assess the clinical outcome of three schemes of HDR-BT boost.Methods and MaterialsRetrospective single institution data collection was performed. Patients received 46 Gy EBRT then an HDR-BT boost: 3 × 6 Gy, 2 × 9 Gy, or 1 × 14 Gy. HDR needles were placed under general anesthesia with endorectal ultrasonography guidance. CT-scan and treatment were performed postoperatively.ResultsBetween 2009 and 2012, 159 patients were included. Nine patients (5.7%) were low, 32 (20.1%) intermediate, and 118 (74.2%) high risk (D'Amico classification) without significant difference between the three BT schemes. With a median followup of 61 months, 5-year biochemical relapse–free survival, 5-year local relapse–free survival, 5-year metastases-free survival, and 5-year overall survival rates were 86.6% (SE 2.7%), 98.3% (SE 1%), 95.3% (SE 1%), and 96.5% (SE 1.5%), respectively, with no significant difference between the BT schemes. The rates of acute ≥ G2 genitourinary and ≥G2 gastrointestinal toxicities were 11.3% and 6.3%, respectively (p = NS). The rates of late genitourinary ≥ G2 and gastrointestinal ≥ G2 toxicities (at last followup) were 9.4% and 0.6% with, respectively, 0.6% and 0% of G4 (p = NS).ConclusionsHypofractionation up to a single-fraction HDR-BT boost for prostate cancer yields similar results in terms of biochemical control and late toxicity compared with two or three-fraction schemes. Single fraction HDR-BT appears acceptable for boosting prostate cancer after definitive EBRT.
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Ban Genital Surgery on Intersex Children, U.S. Rights Group Says
Reuters Health Information
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Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumors
Abstract
Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and an aggressive neoplasm that arises from mesothelium of the pleura. The prognosis is poor with the overall median survival of 9-11 months1. For the diagnosis of MPM, differentiating MPM from pleural metastatic tumors is important.
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Short-term and long-term clinical outcomes of uncommon types of invasive breast cancers
Abstract
Background
Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are predominant and well-documented types of invasive breast cancers (IBC). However, clinical outcomes of other types of IBC (i.e., uncommon IBC), which collectively account for about 20% of all IBC cases, are largely unknown.
Methods
We identified all IBC cases diagnosed in 2004-2006 (n=159,293) and 2010-2011 (n=118,822) from the Surveillance, Epidemiology and End Results (SEER) database. Uncommon IBC included mixed IDC and ILC (MDLC), IDC mixed with other types of carcinoma (IDC-MO), ILC mixed with other types of carcinoma (ILC-MO), and other-type of breast cancers (OC). We estimated overall survivals (OS) and cancer-specific survivals in multivariate regression models.
Results
Compared with IDC, MDLC was associated with a better OS (adjusted hazard ratio [aHR]=0.92, P<0.001 at approximately 10-year follow-up; aHR=0.88, P=0.01 at approximately 4-year follow-up) while OC had a worse OS (aHR=1.06, P=0.005 at approximately 10-year follow-up; aHR=1.23, P<0.001 at approximately 4-year follow-up). Other uncommon IBCs had an OS similar to IDC. Heterogeneity in survivals was observed in some subtypes of OC, with better OS in MDLC and tubular carcinoma. Radiotherapy extended OS for all types of IBC in older women (50+ years). For younger women (<50 years), radiotherapy improved OS in women with IDC, but not ILC or uncommon IBC. Radiotherapy did not change cancer-specific survival of any IBC in younger women.
Conclusions
Uncommon IBCs have distinct patterns in prognosis and survival. Effectiveness of radiotherapy in women with uncommon IBC may differ by age. The underlying mechanisms warrant further studies.
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Topical tocopherol for the treatment of ROLP: randomozed,double-blind crossover study - A query
Abstract
In a recently published study “Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study” (Oral Diseases, January 2017), the authors have assessed the efficacy of topical tocopherol acetate in improving the lesions and oral discomfort of patient's suffering from reticular oral lichen planus comparing it with the results achievable by administering placebo. (1)
In the study, 34 patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate, the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale (VAS).
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Two-Year Results of the Prospective Spine Treatment Outcomes Study: An Analysis of Complication Rates, Predictors of Their Development, and Effect on Patient Derived Outcomes at 2 Years for Surgical Management of Cervical Spondylotic Myelopathy
Publication date: October 2017
Source:World Neurosurgery, Volume 106
Author(s): Michael C. Gerling, Kris Radcliff, Robert Isaacs, Kristina Bianco, Cyrus M. Jalai, Nancy J. Worley, Jaspreet Parmar, Gregory W. Poorman, Samantha R. Horn, John Y. Moon, Paul M. Arnold, Alexander R. Vaccaro, Peter Passias
ObjectivesTo investigate the baseline patient characteristics, nonoperative modalities, surgical procedures, and complications rates of surgical cervical spondylotic myelopathy (CSM) patients. To evaluate risk factors for developing complications and compare the changes in health-related quality of life (HRQOL) from baseline to 2 years postoperatively.MethodsA retrospective review was performed on a prospectively collected database of CSM patients. Baseline patient demographic data, comorbidities, clinical information, nonoperative treatment modalities, surgical procedures, and complication rates were collected. HRQOL outcomes were assessed using the Short Form 36 (SF-36) Physical Score Component (PCS) and Mental Score Component (MCS) and the Neck Disability Index (NDI) at baseline and 2 years postoperatively. Statistical analyses included paired-sample t tests and multivariate logistic regression controlling for age, sex, and body mass index (BMI).ResultsA total of 203 surgical CSM patients were identified (43% female). Average age was 57.7 years and average BMI was 29.6 kg/m2. Before surgical intervention, patients underwent various nonoperative treatment modalities, most commonly nonsteroidal anti-inflammatory drugs (34%), analgesics (32%), and physical therapy (26%). The overall rate of complications was 7.4%. Complications included cerebrospinal fluid leak (2.5%), postoperative radiculopathy (1.0%), and excessive bleeding (1.0%). A previous history of cervical spine surgery was the sole significant risk factor for developing a complication (odds ratio, 9.22; P = 0.034). Average HRQOL scores improved significantly from baseline to 2 years postsurgery.ConclusionsThe overall complication rate was 7.4% for the cohort. Baseline clinical information, comorbidities, use of nonoperative treatment modalities, and procedure type were not significantly associated with an increased risk of complications. Previous cervical spine surgery increased the risk of complications by 9-fold. The patients showed significantly improved SF-36 PCS, SF-36 MCS, and NDI scores at 2 years after surgery.
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Source:World Neurosurgery, Volume 106
Author(s): Michael C. Gerling, Kris Radcliff, Robert Isaacs, Kristina Bianco, Cyrus M. Jalai, Nancy J. Worley, Jaspreet Parmar, Gregory W. Poorman, Samantha R. Horn, John Y. Moon, Paul M. Arnold, Alexander R. Vaccaro, Peter Passias
ObjectivesTo investigate the baseline patient characteristics, nonoperative modalities, surgical procedures, and complications rates of surgical cervical spondylotic myelopathy (CSM) patients. To evaluate risk factors for developing complications and compare the changes in health-related quality of life (HRQOL) from baseline to 2 years postoperatively.MethodsA retrospective review was performed on a prospectively collected database of CSM patients. Baseline patient demographic data, comorbidities, clinical information, nonoperative treatment modalities, surgical procedures, and complication rates were collected. HRQOL outcomes were assessed using the Short Form 36 (SF-36) Physical Score Component (PCS) and Mental Score Component (MCS) and the Neck Disability Index (NDI) at baseline and 2 years postoperatively. Statistical analyses included paired-sample t tests and multivariate logistic regression controlling for age, sex, and body mass index (BMI).ResultsA total of 203 surgical CSM patients were identified (43% female). Average age was 57.7 years and average BMI was 29.6 kg/m2. Before surgical intervention, patients underwent various nonoperative treatment modalities, most commonly nonsteroidal anti-inflammatory drugs (34%), analgesics (32%), and physical therapy (26%). The overall rate of complications was 7.4%. Complications included cerebrospinal fluid leak (2.5%), postoperative radiculopathy (1.0%), and excessive bleeding (1.0%). A previous history of cervical spine surgery was the sole significant risk factor for developing a complication (odds ratio, 9.22; P = 0.034). Average HRQOL scores improved significantly from baseline to 2 years postsurgery.ConclusionsThe overall complication rate was 7.4% for the cohort. Baseline clinical information, comorbidities, use of nonoperative treatment modalities, and procedure type were not significantly associated with an increased risk of complications. Previous cervical spine surgery increased the risk of complications by 9-fold. The patients showed significantly improved SF-36 PCS, SF-36 MCS, and NDI scores at 2 years after surgery.
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Thrombocytopenia and Neurosurgery: A Literature Review
Source:World Neurosurgery, Volume 106
Author(s): Daphne Li, Taylor Glor, G. Alexander Jones
IntroductionThe absence of evidence-based guidelines for platelet transfusion surrounding invasive neurosurgical procedures leads to uncertainty in management. Multiple studies have illuminated this lack of high quality data, and subsequent reliance on expert opinion. The generally accepted threshold for platelet transfusion has hovered around 100,000/μL.MethodsWe have conducted a review of available clinical literature to identify any evidence that may support or refute these general guidelines, in an attempt to clarify the need for platelet transfusion in the patient requiring neurosurgical intervention.ResultsThe available evidence is sparse and of low quality, but suggests that a platelet count <100,000/μL is associated with increased risk of hemorrhagic complications. In addition, the acuity of thrombocytopenia, magnitude of decrease in platelet count, and responsiveness to platelet transfusions impact the risk of neurosurgical intervention, and should be taken into account when evaluating a patient's surgical candidacy. Higher quality, prospective studies on the subject are unlikely, given a general lack of clinical equipoise on the subject, and the ethical concerns such a study would present.
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Endoscopic Submandibular Retropharyngeal Approach to the Craniocervical Junction and Clivus: an Anatomic Study
Source:World Neurosurgery, Volume 106
Author(s): Henri Salle, George de Albuquerque Cavalcanti Mendes, Clément Gantois, Justine Lerat, Nouman Aldahak, François Caire
IntroductionSurgery of the craniocervical junction (CCJ) and clivus is technically demanding. For many years, we have used the submandibular retropharyngeal approach for surgery of the upper cervical spine, especially hangman fracture. We hypothesized that submandibular gland resection could offer a significant cranial enlargement of the operative field, up to the clivus. Our aim in this work was to assess the feasibility of an endoscope-assisted retropharyngeal approach to the CCJ and clivus.MethodsEight anatomic specimens were used, including 4 silicon-injected specimens. We performed a submandibular retropharyngeal approach with gland resection, and then we exposed the CCJ and clivus. We drilled the C2 vertebral body, odontoid process, C1 anterior arch, and the clivus. We noted 8 anatomic landmarks that were easily identified on each anatomic specimen. These measurements were designed to quantify the exposure of the clivus and CCJ after bone resection.ResultsA submandibular approach was feasible in all specimens. The main dimensions of the area of dural exposure after bone drilling were as follows: mean width between C1 lateral masses, 19 mm (range, 17–20 mm); at the tip of the clival window, 18 mm (range, 16–20 mm); distance between the C3 vertebra and the tip of the window within the clivus, 57 mm (range, 55–60 mm).ConclusionsAn endoscopic submandibular retropharyngeal approach provides a simple and straightforward access to the CCJ. It also conveniently exposes the clivus. This technique could be added to the techniques used for this difficult surgery.
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