Σάββατο 9 Απριλίου 2016
Introduction of a new laparoscopic trocar for insertion of peritoneal dialysis catheters and making a proper rectus sheath tunneling
Abstract
Background
Using a proper laparoscopic trocar for making a downward rectus sheet tunneling (RSHT) during the implementation of peritoneal dialysis (PD) catheters leads to a longer survival of catheter and less catheter dysfunction. As no specific laparoscopic trocar has been invented for insertion of PD catheters, we designed a new trocar. In this article, we describe specifications of our new invented trocar for the first time. We will describe our experience with it in our patients as well.
Methods
The new stainless steel trocar includes a cannula and a mandarin. The cannula consists of a tube pipe and head. The tube pipe is so long that is proper for rectus sheet tunneling, and its internal diameter is fitted for easy passage of the catheter with its cuffs. The head consists of two steel parts holding a unidirectional plastic valve preventing backflow of the air. The mandarin section includes a sharp shaft and a metal cap. The distal end of the mandarin is an atraumatic conical tip which was designed to make a safe RSHT.
Results
A total of 30 PD catheters were successfully implanted through 30 laparoscopic procedures in 12 males and 18 females (mean age 48.16 ± 14.18 years). All catheters were successfully inserted without any intraoperative complication. Exit-site infection, peri-catheter leakage, and outflow failure were found in two, one, and one patient, respectively. We did not find any inflow failure, catheter malpositioning, migration, or kinking. No other complication was observed during the 1-year follow-up period.
Conclusion
The new designed PD trocar is a proper port for laparoscopic implantation of the peritoneal dialysis catheter. It is a safe and easy handle trocar that helps surgeons to make an appropriate rectus sheath tunneling with minimal complications.
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Optical coherence tomography (OCT) prior to peroral endoscopic myotomy (POEM) reduces procedural time and bleeding: a multicenter international collaborative study
Abstract
Background
Per-oral endoscopic myotomy (POEM) has emerged as an endoscopic treatment of achalasia. There are no pre-procedural imaging modalities to predict the safest and the most efficacious approach.
Aim
To evaluate the use of optimal coherence tomography (OCT) in providing a pre-procedural esophageal assessment.
Methods
Patients undergoing POEM from July 2013 to November 2015 were captured in a multicenter, international registry. Patients who underwent OCT pre-POEM ("OCT arm") were compared to patients without pre-POEM OCT ("control arm"). OCT images were assessed for the degree of vascularity and the thickness of the circular muscular layer, and an approach was determined.
Results
A total of 84 patients were captured in the registry. Fifty-one patients underwent pre-POEM OCT. Using OCT as a guide, 24 (47 %) of patients underwent anterior POEM while 27 (53 %) underwent posterior POEM. Technical success was achieved in 96 % of patients. Significantly less bleeding occurred in the OCT arm when compared to the control group [4 (8 %) vs. 14 (43 %), p = 0.0001]. As a result, procedural time was significantly lower in the OCT group as compared to the control group (85.8 vs. 121.7 min, p = 0.000097).
Conclusion
Pre-POEM OCT results in a reduction in procedural bleeding which contributes to a reduction in overall procedural time.
Clinical trial registration
NCT01438385.
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New device for transrectal trocar placement and rectal sealing for NOTES: a porcine in vivo and human cadaver study
Abstract
Background
To date, hybrid NOTES, combining transvaginal and laparoscopic access, represents the most popular clinically applied NOTES approach enabling surgical handling comparable to laparoscopic surgery. The transrectal route could be used in a similar way; however, suitable devices facilitating feasible transrectal access and rectal sealing are lacking.
Methods
In collaboration with Karl Storz GmbH, we tailored a rectoscope and trocars to facilitate transrectal trocar placement and rectal sealing for hybrid NOTES procedures using rigid instruments. Five German Landrace pigs underwent transrectal hybrid NOTES cholecystectomy using the new devices. In a second experiment, the transferability to human anatomy was assessed in a human cadaver.
Results
Using the new devices, transrectal trocar placement and rectal sealing proved to be feasible in both experiments. Transrectal hybrid NOTES cholecystectomy could be performed without complications.
Conclusion
The presented devices provide a tailored operating platform allowing precise transrectal trocar insertion and feasible sealing of the rectotomy. Consequently, these new instruments may pave the way for transrectal hybrid NOTES procedures and could succeed to clinical use in future.
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Patent blue V and indocyanine green for fluorescence microimaging of human peritoneal carcinomatosis using probe-based confocal laser endomicroscopy
Abstract
Background
Peritoneal carcinomatosis is a metastatic stage aggravating abdominal and pelvic cancer dissemination. The preoperative evaluation of lesions remains difficult today. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic images of tissue architecture and cellular details. This technology allows in vivo histological interpretation of tissue. The main limitation of pCLE for adoption in the clinic is the unavailability of fluorescent contrast agents. The aim of our study was to evaluate the staining performance of indocyanine green and patent blue V for histological diagnosis of pCLE images of pathological and non-pathological peritoneal tissue.
Methods
We performed a correlative study with the histological gold standard on ex vivo human specimens from 25 patients operated for peritoneal carcinomatosis; 70 specimens were stained by topical application with ICG or patent blue V and then imaged with a probe-based confocal laser endomicroscope. A total of 350 pCLE images and 70 corresponding histological sections were randomly and blindly interpreted by two pathologists (PT1 and PT2). The images were first classified into two categories, tumoral versus non-tumoral, and a refined histological diagnosis was then given.
Results
All presented images were interpreted by PT1 (who received prior training on PCLE image reading) and PT2 (no training). 100 % sensitivity for PT1 and PT2 was noticed with tissues stained with ICG to differentiate tumoral and non-tumoral tissue. Global scores were always better for PT1 (major concordance between 86 and 94 %) than for PT2 (major concordance between 77 and 89 %) independently of the fluorescent dye when histological diagnosis was done on pCLE images.
Conclusion
In conclusion, the pair ICG-pCLE offers the best combination for a non-trained pathologist for the interpretation of pCLE images from peritoneum.
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Optimizing laboratory-based radon flux measurements for sediments
Source:Journal of Environmental Radioactivity, Volumes 158–159
Author(s): Supitcha Chanyotha, Chutima Kranrod, Rawiwan Kritsananuwat, Derek Lane-Smith, William C. Burnett
Radon flux via diffusion from sediments and other materials may be determined in the laboratory by circulating air through the sample and a radon detector in a closed loop. However, this approach is complicated by the necessity of having to determine the total air volume in the system and accounting for any small air leaks that can arise if using extended measurement periods. We designed a simple open-loop configuration that includes a measured mass of wet sediment and water inside a gas-tight reaction flask connected to a drying system and a radon-in-air analyzer. Ambient air flows through two charcoal columns before entering the reaction vessel to eliminate incoming radon. After traveling through the reaction flask, the air passes the drier and the radon analyzer and is then vented. After some time, the radon activity will reach a steady state depending upon the airflow rate. With this approach, the radon flux via diffusion is simply the product of the steady-state radon activity (Bq/m3) multiplied by the airflow rate (mL/min). We demonstrated that this setup could produce good results for materials that produce relatively high radon fluxes. We also show that a modified closed system approach, including radon removal of the incoming air by charcoal filtration in a bypass, can produce very good results including samples with very low emission rates.
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Impact from indoor air mixing on the thoron progeny concentration and attachment fraction
Source:Journal of Environmental Radioactivity, Volumes 158–159
Author(s): G. de With, P. de Jong
Despite the considerable amount of work in the field of indoor thoron exposure, little studies have focussed on mitigation strategies to reduce exposure to thoron and its progeny. For this reason an advanced computer model has been developed that describes the dispersion and aerosol modelling from first principal using Computational Fluid Dynamics. The purpose of this study is to investigate the mitigation effects from air mixing on the progeny concentration and attachment with aerosols. The findings clearly demonstrate a reduction in thoron progeny concentration due to air mixing. The reduction in thoron progeny is up to 60% when maximum air mixing is applied. In addition there is a reduction in the unattached fraction from 1.2% under regular conditions to 0.3% in case of maximum mixing.
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Colposcopic Appearance of Primary Tuberculosis of Cervix- Case Report
2016-04-09T09-42-37Z
Source: The Southeast Asian Journal of Case Report and Review
Dipanwita Banerjee, Birinchi kumar Saikia, Ranajit Mandal,Priyatosh K Dey, Pradip Das, Partha Basu.
Introduction: Primary tuberculosis of cervix is a rare disease with a very few case reported in the literature till date. Mostly seen in the developing world, colposcopy appearance of the affected cervix may mislead the treating physician towards carcinoma cervix until the histopathology report reveals this non neoplastic condition. Case report: We presented a case of post menopausal lady with chief complaint of persistent vaginal discharge with colposcopy findings of leukoplakia on cervix with surface irregularity which was not acetowhite and was devoid of any vessel abnormality. The patient was treated with 6 months of anti tubercular drug after cervix histology was positive for primary tuberculosis and got cured completely. Conclusion: The unique presentation of leukoplakia without any malignant changes makes our case special as till date no cases of leukoplakia with a background of cervix tuberculosis has been reported in the literature.
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Poststroke Aphasia Frequency, Recovery, and Outcomes: a systematic review and meta-analysis
Publication date: Available online 8 April 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Heather L. Flowers, Stacey A. Skoretz, Frank L. Silver, Elizabeth Rochon, Jiming Fang, Constance Flamand-Roze, Rosemary Martino
ObjectiveWe conducted a systematic review to elucidate the frequency, recovery, and associated outcomes for poststroke aphasia over the long-term.Data SourcesUsing the Cochrane Stroke Strategy, we searched 10 databases, 13 journals, 3 conferences, and the grey literature.Study SelectionOur a priori protocol criteria included unselected samples of adult stroke patients from randomized controlled trials or consecutive cohorts. Two independent reviewers rated abstracts and articles for exclusion or inclusion, resolving discrepancies by consensus.Data ExtractionWe documented aphasia frequencies by stroke type and setting and computed odds ratios (OR) with their 95 percent confidence intervals (CI) for outcomes.Data SynthesisWe retrieved 2168 citations, reviewed 248 articles, and accepted 50. Median frequencies for mixed stroke (ischemic and hemorrhagic) were 30 and 34 percent for acute and rehabilitation settings, respectively. Frequencies by stroke type were lowest for acute subarachnoid hemorrhage (9%) and highest for acute ischemic stroke (62%) when arrival to hospital was ≤3 hours from stroke onset. Articles monitoring aphasia for one year demonstrated aphasia frequencies 2 to 12 percent lower than baseline. Negative outcomes associated with aphasia included greater odds of in-hospital death (OR 2.7, CI 2.4-3.1) and longer mean length of stay in days (M 1.6, CI 1.0-2.3) in acute settings. Patients with aphasia had greater disability from 28 days (OR 1.5, CI 1.3-1.7) to two years (OR 1.7, CI 1.6-2.0) than those without aphasia. By two years, they used more rehabilitation services (OR 1.5, CI 1.3-1.6) and returned home less frequently (OR 1.4, CI 1.2-1.7).ConclusionsReported frequencies of poststroke aphasia range widely, depending on stroke type, and setting. Because aphasia is associated with mortality, disability, and use of health services, we recommend long-term interdisciplinary vigilance in the management of aphasia.
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Men and Women Demonstrate Differences in Early Functional Recovery After Total Knee Arthroplasty
Publication date: Available online 8 April 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Allison M. Gustavson, Pamela Wolfe, Jason R. Falvey, Donald G. Eckhoff, Michael J. Toth, Jennifer E. Stevens-Lapsley
ObjectiveTo investigate whether sex impacts the trajectory of functional recovery following total knee arthroplasty (TKA).DesignRetrospective analysis from a historical database containing data from three prospective clinical trials and a pilot study.SettingAll studies were performed in a clinical laboratory setting.ParticipantsRecruitment across studies was restricted to patients who underwent an elective unilateral TKA for the treatment of osteoarthritis and were between 50-85 years of age (N=301).InterventionAcross all four studies patients received a TKA and physical therapy intervention. Measures of physical function and strength were assessed prior to TKA, 1, 3, and 6 months after TKA.Main Outcome MeasuresStatistical inference using a maximum likelihood model for repeated measures was done to estimate the changes in outcomes by sex from pre-surgical assessment compared to 1, 3, and 6 months after TKA. Muscle strength was assessed during maximal isometric quadriceps and hamstrings contractions. Muscle activation was assessed in the quadriceps muscle. Physical function outcomes included: Timed-Up-and-Go (TUG), Stair Climbing Test (SCT), and the Six-Minute Walk Test (6MWT).ResultsWomen demonstrated less decline in quadriceps strength than men at 1, 3, and 6 months after TKA (p<0.04), whereas women demonstrated less decline in hamstrings strength 1 month after TKA (p<0.0001). Women demonstrated a greater decline than men on the TUG (p=0.001), SCT (p=0.004), and 6MWT (p=0.001) 1 month after TKA. Sex differences in physical function did not persist at 3 and 6 months following TKA.ConclusionsSex impacted early recovery of muscle and physical function within the first month after TKA. Women demonstrated better preservation of quadriceps strength, but demonstrated greater decline on measures of physical function compared to men.
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DNA and chromosomal damage in medical workers exposed to anaesthetic gases assessed by the lymphocyte Cytokinesis-Block Micronucleus (CBMN) assay. A critical review.
Publication date: Available online 8 April 2016
Source:Mutation Research/Reviews in Mutation Research
Author(s): Pavel Vodicka, Ludovit Musak, Giovanni Fiorito, Veronika Vymetalkova, Ludmila Vodickova, Alessio Naccarati
The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed either environmentally or occupationally to genotoxic chemicals. However, there is an emerging need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to main classes of chemical genotoxins.The main aim of the present report is to systematically review published studies investigating the use of the lymphocyte CBMN assay to determine DNA damage in subjects exposed to anaesthetic gases. We also compared performance of the CBMN assay with other DNA damage assays employed and identified strengths and weaknesses of the published studies. We have retrieved 11 studies, published between 1996 and 2013, reporting MN associated with occupational exposures (operating room personnel). The individual job categories were often described (anaesthesiologists, technicians, radiologists) among cases, as well as duration of exposure. All studies reported the compounds present at the workplace and, in some instances, the exposure levels were measured. Controls were usually recruited among personnel of the hospital not exposed to anaesthetics or they were healthy unexposed subjects from general population. The number of investigated subjects, due to the character of the occupation, was relatively smaller than those investigated in other occupational monitoring settings. Overall, the majority of the studies were age- and gender- matched (or investigated only males or females) while less attention was given to lifestyle confounders. Appropriate measurement of exposure, available in approximately half of the studies only, was compromised by the lack of the personal dosimetry-based determinations.In all studies, higher MN frequencies were observed in exposed individuals. The meta-analysis of mean MN frequency of combined studies confirmed this tendency (log mean ratio=0.56 [0.34-0.77]; P=3.51×10−7). Similar differences between the exposed and controls were also observed for other biomarkers.
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Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?
Abstract
Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.
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Double spinal cord lesions and pelvic floor electrophysiology
Source:Clinical Neurophysiology, Volume 127, Issue 5
Author(s): David B. Vodušek
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Editorial Board
Source:Clinical Neurophysiology, Volume 127, Issue 5
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Pelvic floor electrophysiology in spinal cord injury
Source:Clinical Neurophysiology, Volume 127, Issue 5
Author(s): H. Tankisi, K. Pugdahl, M.M. Rasmussen, D. Clemmensen, Y.F. Rawashdeh, P. Christensen, K. Krogh, A. Fuglsang-Frederiksen
ObjectiveThe study aimed to investigate sacral peripheral nerve function and continuity of pudendal nerve in patients with chronic spinal cord injury (SCI) using pelvic floor electrophysiological tests.MethodsTwelve patients with low cervical or thoracic SCI were prospectively included. Quantitative external anal sphincter (EAS) muscle electromyography (EMG), pudendal nerve terminal motor latency (PNTML) testing, bulbocavernosus reflex (BCR) testing and pudendal short-latency somatosensory-evoked potential (SEP) measurement were performed.ResultsIn EAS muscle EMG, two patients had abnormal increased spontaneous activity and seven prolonged motor unit potential duration. PNTML was normal in 10 patients. BCR was present with normal latency in 11 patients and with prolonged latency in one. The second component of BCR could be recorded in four patients. SEPs showed absent cortical responses in 11 patients and normal latency in one.ConclusionsPudendal nerve and sacral lower motor neuron involvement are significantly associated with chronic SCI, most prominently in EAS muscle EMG. The frequent finding of normal PNTML latencies supports earlier concerns on the utility of this test; however, BCR and pudendal SEPs may have clinical relevance.SignificanceAs intact peripheral nerves including pudendal nerve are essential for efficient supportive therapies, pelvic floor electrophysiological testing prior to these interventions is highly recommended.
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The Association of Changes in Sedentary Behavior on Changes in Depression Symptomology: Pilot Study
2016-04-09T07-18-16Z
Source: Journal of Behavioral Health
Paul D. Loprinzi, Eveleen Sng.
Objective: It is well established that physical activity is inversely associated with depression symptoms. Emerging work demonstrates that, independent of physical activity, sedentary behavior is associated with unfavorable cardiometabolic parameters. Recent work, albeit limited, has observed an independent association of sedentary behavior and depression symptoms. However, no study, to our knowledge, has examined the influences of changes in sedentary behavior on changes in depression symptom, which was the purpose of this pilot study. Methods: In this pilot study, 29 adults (Agemean = 36.8; 79% female) completed a survey at baseline and again approximately 2-months later. Sedentary behavior (TV and computer use) and depression (PHQ-9), along with potential confounders (e.g., physical activity, anxiety), were subjectively assessed. Results: In a series of nested, sequential multivariable regression models, increases in sedentary behavior over the follow-up period was associated with increased depression symptomology (βadjusted = 0.65; 95% CI: 0.06-1.23; P=0.03). There was no evidence to suggest a bi-directional relationship, in that changes in depression was not associated with follow-up sedentary behavior (β = 0.31; 95% CI: -0.08-71; P=0.11). Conclusion: Increases in sedentary behavior were associated with increased depression symptomology. Future replicative work is needed.
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Prevalence of Depressive Disorders in Children with Specific Learning Disabilities
2016-04-09T07-18-16Z
Source: Journal of Behavioral Health
Mona P Gajre, Himali Meshram,Neelkamal Soares,Ms Chedda Nidhi* Afreddy Anagha*.
Prevalence of Depressive Disorders in Children With Specific Learning Disabilities Background: Learning disabled children are at risk for behavioral disorders, including depression. In India, diagnosis and interventions for learning disorders are limited.The purpose of the present study was to examine the prevalence of depression and its severity in school-aged children with specific learning disability (SLD) compared to non-learning disabled peers. Methods: In a tertiary care pediatric neurodevelopmental centre in Mumbai, we identified 200 children consecutively over twelve months referred for low academic performance, by screening of clinical records, academic history, vision-hearing tests, who additionally underwent psychoeducational battery and cognitive testing at the center, and were determined to have average intelligence . but meeting criteria for Specific Learning Disability (SLD). The controls were 100 siblings of the children who were screened for SLD by curriculum based tests.. We assessed depression using Hamilton Rating Scale for Depression (HDRS for 8-12 years) and Beck Depression Inventory II (BDI for 13-14 years).Additionally parental history of prescription medications for mental health needs was also noted. We performed multivariate logistic regression to study the association between SLD and depression. All activities were approved by the Institutional Review Board. Results: The mean (S D) age of children with SLD was 11.9 (1.6) years and of non-SLD children was 11.2 (1.2) years.In SLD group the M:F ratio was 1.5:1 and in the non SLD it was 0.8:1. A significantly higher proportion of children with SLD reported that their academic and extracurricular activities were reduced compared to children without SLD (6% vs 0%, p
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Anchored pseudo-de novo assembly of human genomes identifies extensive sequence variation from unmapped sequence reads
Abstract
The human genome reference (HGR) completion marked the genomics era beginning, yet despite its utility universal application is limited by the small number of individuals used in its development. This is highlighted by the presence of high-quality sequence reads failing to map within the HGR. Sequences failing to map generally represent 2–5 % of total reads, which may harbor regions that would enhance our understanding of population variation, evolution, and disease. Alternatively, complete de novo assemblies can be created, but these effectively ignore the groundwork of the HGR. In an effort to find a middle ground, we developed a bioinformatic pipeline that maps paired-end reads to the HGR as separate single reads, exports unmappable reads, de novo assembles these reads per individual and then combines assemblies into a secondary reference assembly used for comparative analysis. Using 45 diverse 1000 Genomes Project individuals, we identified 351,361 contigs covering 195.5 Mb of sequence unincorporated in GRCh38. 30,879 contigs are represented in multiple individuals with ~40 % showing high sequence complexity. Genomic coordinates were generated for 99.9 %, with 52.5 % exhibiting high-quality mapping scores. Comparative genomic analyses with archaic humans and primates revealed significant sequence alignments and comparisons with model organism RefSeq gene datasets identified novel human genes. If incorporated, these sequences will expand the HGR, but more importantly our data highlight that with this method low coverage (~10–20×) next-generation sequencing can still be used to identify novel unmapped sequences to explore biological functions contributing to human phenotypic variation, disease and functionality for personal genomic medicine.
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Social determinants of motivation to lose weight among literate obese patients: A qualitative study
2016-04-09T03-23-35Z
Source: Journal of Behavioral Health
Ayodele Emmanuel Oyebanji, Musa Dankyau, Osesienemo Asiribo-Sallau.
Background: The study of motivation is central to understanding and identifying patients who are likely to benefit from obesity interventions. Previous studies have demonstrated the efficacy of an outpatient counselling technique in improving motivation to change among literate obese patients. The reasons for this demonstrated efficacy needs to be explored to guide policy and practice of obesity interventions. Methods: A total of 18 obese individuals were recruited by purposive sampling into three groups of six individuals each matched for Readiness to Change (RTC) group based on URICA Score, age group and gender. Focus group discussions using open-ended questions to elucidate which factors could potentially be correlated with participants motivation, were moderated between July and October 2012. Data was recorded manually and with an MP3 recorder. Thematic analysis was used to generate themes and a derived model in January 2013. Results: The key themes generated from the focus group discussion include: Pressure from family, friends and society; Dressing, stigmatization and self-esteem; Recognition of risk factors for diseases; Counselling by the physician: Economic factors: and having a weight loss programme in the hospital. Conclusion: Mixed extrinsic and intrinsic factors play a role in motivation to lose weight among literate obese patients in a primary care setting. Extrinsic factors (peer, family and societal pressure; cash incentives; counselling by physician; and hospital weight loss programme) were however predominant. These findings have implications for clinicians involved in weight management programmes, and policy makers seeking public health interventions for obesity prevention need to consider interventions targeted on extrinsic motivations.
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Exaggerated hemodynamic and neural responses to involuntary contractions induced by whole body vibration in normotensive obese vs. lean women
In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we aimed at examining whether involuntary mechanical oscillations, induced by whole-body-vibration (WBV), elicit greater hemodynamic responses and altered neural control of BP, in obese vs. lean women. Twenty-two normotensive, pre-menopausal women (lean = 12, obese = 10) performed randomly a passive WBV (25 Hz) and a control (similar posture without WVB) protocol. Beat-by-beat BP, heart rate (HR), stroke volume, systemic vascular resistance (SVR), cardiac output, parasympathetic output [evaluated by heart rate variability (HRV)] and spontaneous baroreceptor sensitivity (sBRS) were assessed. Results: During WBV, obese exhibited an augmented systolic BP response vs. lean that was correlated with body fat percentage (R = 0.77; p<0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese vs. lean, associated with a greater stroke volume index in obese. Involuntary contractions did not elicit a differential magnitude of responses in HR, HRV indices, and SVR in obese vs. lean; however, they did result in greater sBRS responses (p<0.05) in obese. Conclusions: Involuntary contractions elicited an augmented BP and sBRS response in normotensive obese vs. lean. The greater elevations in circulatory hemodynamics in obese, are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.
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The rat suprachiasmatic nucleus: The master clock ticks at 30 Hz
Abstract
The suprachiasmatic nucleus (SCN) of the hypothalamus has an essential role in orchestrating circadian rhythms of behaviour and physiology. In the present study, we recorded from single SCN neurons in urethane-anesthetised rats, categorized them by statistical features of their electrical activity and by their responses to light, and examined how activity in the light phase differs from activity in the dark phase. We classified cells as light-on cells or light-off cells according to how their firing rate changed in acute response to light, or as non-responsive cells. In both sets of light-responsive neurons, responses to light were stronger at subjective night than in subjective day. Neuronal firing patterns were analysed by constructing hazard functions from interspike interval data. For most light-responsive cells, the hazard functions showed a multimodal distribution, with a harmonic sequence of modes, indicating that spike activity was driven by an oscillatory input with a fundamental frequency of close to 30 Hz; this harmonic pattern was rarely seen in non-responsive SCN cells. The frequency of the rhythm was the same in light-on cells as in light-off cells, the same in subjective day as at subjective night, and was unaffected by exposure to light. Paired recordings indicated that the discharge of adjacent light-responsive neurons was very tightly synchronized, consistent with electrical coupling.
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Rac1 governs exercise-stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice
Abstract
Exercise increase skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signaling mechanisms vital for glucose uptake during exercise are not yet fully understood but the GTPase Rac1 is a candidate molecule. This study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise-induced uptake of radiolabelled 2-deoxyglucose (2-DG) at 65% max running capacity was blocked in soleus and decreased by 80 and 60% in gastrocnemius and tibialis anterior muscles, respectively, in muscle-specific inducible Rac1 knockout (mKO) mice compared to wildtype littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 mKO muscle. Our findings implicate Rac1 as a regulatory element critical for controlling glucose uptake during exercise via regulation of GLUT4 translocation.
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Biphasic modulation of parallel fiber synaptic transmission by co-activation of presynaptic GABAA and GABAB receptors in mice
Abstract
GABAA and GABAB receptors are co-expressed at many presynaptic terminals in the central nervous system. Previous studies have shown that GABAA receptors typically enhance vesicle release while GABAB receptors inhibit release. However, it is not clear how the competing actions of these receptors modulate synaptic transmission when co-activated, as is likely in vivo. We investigated this question at parallel fiber synapses in the cerebellum, which co-express presynaptic GABAA and GABAB receptors. In acute slices from C57BL/6 mice, we find that co-activation of presynaptic GABA receptors by photolytic uncaging of RuBi-GABA has a biphasic effect on EPSC amplitudes recorded from stellate cells. Synchronous and asynchronous EPSCs evoked within ∼100 ms of GABA uncaging were increased, while EPSCs evoked ∼300–600 ms after GABA uncaging were reduced compared to interleaved control sweeps. We confirmed these effects are presynaptic by measuring the paired-pulse ratio, variance of EPSC amplitudes, and response probability. During trains of high-frequency stimulation GABAA and GABAB receptors work together (rather than oppose one another) to reduce short-term facilitation when GABA is uncaged just prior to the onset of stimulation. We also find that GABAB receptor-mediated inhibition can be elicited by lower GABA concentrations than GABAA receptor-mediated enhancement of EPSCs, suggesting GABAB receptors may be selectively activated by ambient GABA or release from more distance synapses. These data suggest that GABA, acting through both presynaptic GABAA and GABAB receptors, modulate the amplitude and short-term plasticity of excitatory synapses, a result not possible from activation of either receptor-type alone.
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An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats (SHRs)
Abstract
Activation of central chemoreceptors by CO2 increases arterial blood pressure (ABP), sympathetic nerve activity (SNA), and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced SNA and peripheral chemoreflexes. We hypothesized that an augmented CO2 chemoreflex and overactive orexin system are linked with high ABP in both young (P30-58 days) and adult (4–6 months) SHRs. We show: 1) An augmented CO2 chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic-hypercapnia is higher in young SHRs (179 ± 11 SEM % increase) than in age-matched normotensive Wistar-Kyoto (WKY) rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase) (P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age-matched WKY rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg) (P < 0.05). 2) SHRs have more orexin neurons and more CO2-activated orexin neurons in the hypothalamus. 3) Antagonism of orexin receptors with a dual orexin receptor antagonist, almorexant, normalizes the augmented CO2 chemoreflex in young and adult SHRs and the high ABP in young SHRs, and significantly lowers ABP in adult SHRs. 4) Attenuation of peripheral chemoreflexes by hyperoxia does not abolish the augmented CO2 chemoreflex (breathing and ABP) in SHRs, which indicates an important role for the central chemoreflex. We suggest that an overactive orexin system may play an important role in the augmented central CO2 chemoreflex and in the development of hypertension in SHRs.
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Computational Cardiology and Risk Stratification for Sudden Cardiac Death: One of the Grand Challenges for Cardiology in the 21st Century
Abstract
Risk stratification in the context of sudden cardiac death has been acknowledged as one of the major challenges facing cardiology for the past four decades. In recent years, the advent of high performance computing has facilitated organ-level simulation of the heart, meaning we can now examine the causes, mechanisms and impact of cardiac dysfunction in silico. As a result, computational cardiology, largely driven by the Physiome project, now stands at the threshold of clinical utility in regards to risk stratification and treatment of patients at risk of sudden cardiac death. In this white paper, we outline a roadmap of what needs to be done to make this translational step, using the relatively well developed case of acquired or drug-induced long QT syndrome as an exemplar case.
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Evidence of a broad histamine footprint on the human exercise transcriptome
Abstract
Histamine is a primordial signaling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell-surface receptors. In humans, aerobic exercise is followed by a post-exercise activation of histamine H1 and H2 receptors localized to the previously exercised muscle. This could trigger a broad range of cellular adaptations in response to exercise. Thus, we exploited RNA sequencing to explore the effects of H1 and H2 receptor blockade on the exercise transcriptome in human skeletal muscle tissue harvested from the vastus lateralis. We found that exercise exerts a profound influence on the human transcriptome, causing the differential expression of more than 3000 protein-coding genes. The influence of histamine blockade post-exercise was notable for 795 genes which were differentially expressed between the control and blockade condition, which represents > 25% of the number responding to exercise. The broad histamine footprint on the human exercise transcriptome crosses many cellular functions including inflammation, vascular function, metabolism, and cellular maintenance.
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The half-life of infusion fluids: An educational review.
An understanding of the half-life of (T1/2) infused fluids can help prevent iatrogenic problems such as volume overload and postoperative interstitial oedema. Simulations show that a prolongation of the T1/2 for crystalloid fluid increases the plasma volume and promotes accumulation of fluid in the interstitial fluid space. The T1/2 for crystalloids is usually 20 to 40 min in conscious humans but might extend to 80 min or longer in the presence of preoperative stress, dehydration, blood loss of
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Dosing recommendations for pharmacogenetic interactions related to drug metabolism.
Objective: Pharmacogenomic studies have established the important contribution of drug-metabolizing enzyme genotype toward drug toxicity and treatment failure; however, clinical implementation of pharmacogenomics has been slow. The aim of this study was to systematically review the information on drug-metabolizing enzyme pharmacogenomics available in the US drug labeling, practice guidelines, and recommendations. Methods: Drug-metabolizing enzyme genotype and phenotype information was assessed in US FDA drug labeling, clinical practice guidelines, and independent technology assessors to evaluate the consistency in information sources for healthcare providers. Results: Eighty four gene-drug pairs were identified as having drug-metabolizing enzyme genotype or phenotype information within the label. The manner in which pharmacogenomic information was presented was heterogeneous both within the label and between clinical practice recommendations. Conclusion: For proper implementation of pharmacogenomics in clinical practice, information sources for healthcare providers should relay consistent and clear information for the appropriate use of biomarkers. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
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Fragmentation of Care in Ectopic Pregnancy
Abstract
Objectives Ectopic pregnancy is an important cause of maternal morbidity and mortality. Women who experience fragmented care may undergo unnecessary delays to diagnosis and treatment. Based on ectopic pregnancy cases observed in clinical practice that raised our concern about fragmentation of care, we designed an exploratory study to describe the number, characteristics, and outcomes of fragmented care among patients with ectopic pregnancy at one urban academic hospital. Methods Chart review with descriptive statistics. Fragmented care was defined as a patient being evaluated at an outside facility for possible ectopic pregnancy and transferred, referred, or discharged before receiving care at the study institution. Results Of 191 women seen for possible or definite ectopic pregnancy during the study period, 42 (22 %) met the study definition of fragmented care. The study was under-powered to observe statistically significant differences across groups, but we found concerning, non-significant trends: patients with fragmented care were more likely to be Medicaid recipients (65.9 vs. 58.8 %) and to experience a complication (23.8 vs. 18.1 %) compared to those with non-fragmented care. Most patients (n = 37) received no identifiable treatment prior to transfer and arrived to the study hospital with no communication to the receiving hospital from the outside provider (n = 34). Nine patients (21 %) presented with ruptured ectopic pregnancies. The fragmentation we observed in our study may contribute to previously identified socio-economic disparities in ectopic pregnancy outcomes. Conclusion If future research confirms these findings, health information exchanges and regional coordination of care may be important strategies for reducing maternal mortality.
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Psychological Symptoms and Social Functioning Following Repair of Obstetric Fistula in a Low-Income Setting
Abstract
Objectives Obstetric fistula is a maternal injury that causes uncontrollable leaking of urine or stool, and most women who develop it live in poverty in low-income countries. Obstetric fistula is associated with high rates of stigma and psychological morbidity, but there is uncertainty about the impact of surgical treatment on psychological outcomes. The objective of this exploratory study was to examine changes in psychological symptoms following surgical fistula repair, discharge and reintegration home. Methods Women admitted for surgical repair of obstetric fistula were recruited from a Tanzanian hospital serving a rural catchment area. Psychological symptoms and social functioning were assessed prior to surgery. Approximately 3 months after discharge, a data collector visited the patients' homes to repeat psychosocial measures and assess self-reported incontinence. Baseline to follow-up differences were measured with paired t tests controlling for multiple comparisons. Associations between psychological outcomes and leaking were assessed with t tests and Pearson correlations. Results Participants (N = 28) had been living with fistula for an average of 11 years. Baseline psychological distress was high, and decreased significantly at follow-up. Participants who self-reported continued incontinence at follow-up endorsed significantly higher PTSD and depression symptoms than those who reported being cured, and severity of leaking was associated with psychological distress. Conclusions Fistula patients experience improvements in mental health at 3 months after discharge, but these improvements are curtailed when women experience residual leaking. Given the rate of stress incontinence following surgery, it is important to prepare fistula patients for the possibility of incomplete cure and help them develop appropriate coping strategies.
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Developmental Origins, Epigenetics, and Equity: Moving Upstream
Abstract
The Developmental Origins of Health and Disease and the related science of epigenetics redefines the meaning of what constitutes upstream approaches to significant social and public health problems. An increasingly frequent concept being expressed is "When it comes to your health, your zip code may be more important than your genetic code". Epigenetics explains how the environment—our zip code—literally gets under our skin, creates biological changes that increase our vulnerability for disease, and even children's prospects for social success, over their life course and into future generations. This science requires us to rethink where disease comes from and the best way to promote health. It identifies the most fundamental social equity issue in our society: that initial social and biological disadvantage, established even prior to birth, and linked to the social experience of prior generations, is made worse by adverse environments throughout the life course. But at the same time, it provides hope because it tells us that a concerted focus on using public policy to improve our social, physical, and economic environments can ultimately change our biology and the trajectory of health and social success into future generations.
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Growing a Best Babies Zone: Lessons Learned from the Pilot Phase of a Multi-Sector, Place-Based Initiative to Reduce Infant Mortality
Abstract
Purpose Infant mortality reduction in the U.S. has been addressed predominantly through clinical approaches. While these efforts have reduced the infant mortality rate overall, they have not reduced disparities between different racial/socioeconomic groups. To address the interrelated social, economic and environmental factors contributing to infant mortality, a place-based approach is needed to complement existing initiatives and clinical practices. Description Best Babies Zone (BBZ) is an early attempt to put life course theory into practice, taking a place-based approach to reducing infant mortality by aligning resources, building community leadership, and transforming educational opportunities, economic development, and community systems in concentrated neighborhoods. BBZ is currently in three neighborhoods: Price Hill (Cincinnati, OH), Hollygrove (New Orleans, LA), and Castlemont (Oakland, CA). Assessment In its first 4 years, each BBZ crafted resident-driven strategies for decreasing the root causes of toxic stress and poor birth outcomes. To address resident priorities, BBZ sites experimented with tools from other fields (like design thinking and health impact assessment), and emphasized existing MCH strategies like leadership development. Early challenges, including shifting from traditional MCH interventions and addressing health equity, point to areas of growth in implementing this approach in the maternal and child health field. Conclusion BBZ aims to elevate local voice and mobilize multiple sectors in order to address the social determinants of infant mortality, and other initiatives working to improve MCH outcomes can learn from the successes and challenges of the first 4 years of BBZ in order to bring life course theory into practice.
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Head Start Oral Health Assessment
Abstract
Purpose A Head Start program located in Paterson, New Jersey considered establishing a school-based dental clinic to address unmet oral health needs such as access to care and the need for restorative treatment. The purpose of this study was to establish the oral health status of Head Start children, their treatment needs, and parents' interest and willingness to utilize a school-based dental clinic. Description School-based dental care has been used to address access to care issues, particularly among children who live in underserved areas. A 21 item survey was used to correlate the results of an oral exam performed on the Head Start children and the parents' preferences, beliefs and access patterns. Fisher's exact test and Chi squared test were used to study the association among variable with significance levels set at 0.05. Assessment The oral exam revealed a high caries rate amongst all of the children. Parental responses indicated strong support for the establishment of a school-based clinic and identified the need for further parental education. Having a regular source of care was found to be unrelated to treatment needs. Conclusion Further education of the parents regarding the child's oral health is critical to the success and viability of this school-based clinic.
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Healthcare Utilization After a Children’s Health Insurance Program Expansion in Oregon
Abstract
Objective The future of the Children's Health Insurance Program (CHIP) is uncertain after 2017. Survey-based research shows positive associations between CHIP expansions and children's healthcare utilization. To build on this prior work, we used electronic health record (EHR) data to assess temporal patterns of healthcare utilization after Oregon's 2009–2010 CHIP expansion. We hypothesized increased post-expansion utilization among children who gained public insurance. Methods Using EHR data from 154 Oregon community health centers, we conducted a retrospective cohort study of pediatric patients (2–18 years old) who gained public insurance coverage during the Oregon expansion (n = 3054), compared to those who were continuously publicly insured (n = 10,946) or continuously uninsured (n = 10,307) during the 2-year study period. We compared pre-post rates of primary care visits, well-child visits, and dental visits within- and between-groups. We also conducted longitudinal analysis of monthly visit rates, comparing the three insurance groups. Results After Oregon's 2009–2010 CHIP expansions, newly insured patients' utilization rates were more than double their pre-expansion rates [adjusted rate ratios (95 % confidence intervals); increases ranged from 2.10 (1.94–2.26) for primary care visits to 2.77 (2.56–2.99) for dental visits]. Utilization among the newly insured spiked shortly after coverage began, then leveled off, but remained higher than the uninsured group. Conclusions This study used EHR data to confirm that CHIP expansions are associated with increased utilization of essential pediatric primary and preventive care. These findings are timely to pending policy decisions that could impact children's access to public health insurance in the United States.
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Proliposomal Ropivacaine Oil: Pharmacokinetic and Pharmacodynamic Data After Subcutaneous Administration in Volunteers.
BACKGROUND: Slow-release liposomal formulations of local anesthetics prolong plasma redistribution and reduce peak plasma drug concentration, allowing safer administration of larger doses and further prolonging sensory effects. However, their clinical applicability is limited by expensive manufacture and liposomal leakage. Previously, we described the simple preparation of a novel proliposomal ropivacaine oil that produces multilamellar liposomal vesicles on exposure to aqueous media and that has a shelf-life of >2 years at room temperature. In this study, we present both pharmacodynamic and pharmacokinetic data in healthy volunteers after subcutaneous injection of this novel proliposomal preparation of ropivacaine. METHODS: In the pharmacodynamic phase of this study, 15 volunteers received 3 separate subcutaneous injections of 2.5 mL containing 1 of the following drugs: proliposomal 4% ropivacaine, plain 0.5% ropivacaine, and the ropivacaine-free proliposomal vehicle. Drugs were administered into the lower back, and their location was randomized and blinded; a separate area was used as an uninjected, open control. Experimental sensory assessment was made at repeated intervals over 72 hours using both pinprick sensation and experimental heat pain tolerance (assessed using quantitative sensory testing). In a separate pharmacokinetic phase of this study, 9 volunteers received subcutaneous injections of 2.5 mL of either proliposomal 4% ropivacaine (n = 6) or plain 0.5% ropivacaine (n = 3); these participants had plasma ropivacaine concentrations assessed at repeated intervals over 72 hours. RESULTS: The mean +/- SE duration of pinprick anesthesia after proliposomal and plain ropivacaine administration lasted 28.8 +/- 6.0 and 15.9 +/- 3.5 hours, respectively (mean difference, 16.8 hours; 95% confidence interval, 10.0-23.7; P = 0.001). For experimental heat pain, the anesthesia duration was approximately 36 and 12 hours, respectively, with mean +/- SE area under the curve of the normalized heat pain tolerance over time 55.0 +/- 28.8 [DELTA][degrees]C[middle dot]min for proliposomal ropivacaine and 9.6 +/- 26.0 [DELTA][degrees]C[middle dot]min for plain ropivacaine (mean difference, 64.6 [DELTA][degrees]C[middle dot]min; 95% confidence interval, 10.2-119.0; P = 0.036). In the pharmacokinetic study, there was no significant difference in peak plasma concentration in the proliposomal ropivacaine group (164 +/- 43 ng/mL compared with 100 +/- 41 ng/mL in the plain ropivacaine group; P = 0.07) despite an 8-fold increase in ropivacaine dose in the proliposomal group. The 99% upper prediction limit for peak plasma concentrations (351 ng/mL proliposomal; 279 ng/mL plain) was well below the putative toxic plasma concentration for both groups. The mean +/- SE terminal half-life and area under the curve for proliposomal ropivacaine versus plain ropivacaine were 13.8 +/- 3.6 hours vs 5.9 +/- 2.3 hours (P = 0.011) and 5090 +/- 1476 h[middle dot]ng/mL vs 593 +/- 168 h[middle dot]ng/mL (P = 0.0014), respectively. CONCLUSIONS: The prolonged pharmacodynamic effect of proliposomal ropivacaine, together with its delayed elimination and prolonged redistribution to plasma, is compatible to depot-related slow-release and similar to the performance of other liposomal local anesthetics. The advantage of the proliposomal oil is its ease of preparation and its extended shelf-stability at room temperature. (C) 2016 International Anesthesia Research Society
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A Novel Proliposomal Ropivacaine Oil: Pharmacokinetic-Pharmacodynamic Studies After Subcutaneous Administration in Pigs.
BACKGROUND: Liposomal local anesthetics are limited by a short liposomal shelf-life, even when under refrigeration. We describe a novel proliposomal ropivacaine that produces liposomes in situ, only after exposure to aqueous media. METHODS: In vitro: Nanoparticles were assessed (particle size distribution analyzer, cryo-transmission electron microscopy) at baseline and after exposure to saline/plasma. Toxicity: In porcine wound healing study (n = 12), healing was assessed by photography, clinical assessment, and histology. Pharmacodynamics: Seventeen young piglets were randomly assigned to plain 0.5% ropivacaine (n = 5), proliposomal 4% ropivacaine (n = 6), or sham (n = 6). Tactile threshold was assessed using von Frey filaments applied to the surgical wound; the nonoperated skin was used as a control. Tactile threshold over time was determined using area under the curve (AUC) and assessed by 1-way analysis of variance. Pharmacokinetics: 8 young piglets were randomly assigned to plain 0.5% (25 mg, n = 4) or proliposomal 4% (200 mg, n = 4) ropivacaine. Plasma ropivacaine was assessed by high-performance liquid chromatography at baseline and at intervals over 36 hours. Paired ropivacaine concentration (from wound exudate and plasma) was obtained at 96 hours. Data were analyzed using noncompartmental and compartmental models. RESULTS: In vitro: On exposure to saline and plasma, the study drug was transformed from a homogenous oil to an emulsion containing liposomes of approximately 1.4-[mu]m diameter; this effect was dilution dependent and stable over time. Toxicity: All wounds healed well; no effect of drug group was observed. Pharmacodynamics: Plain and proliposomal ropivacaine provided sensory anesthesia for approximately 6 and 30 hours, respectively. There was an approximately 7-fold increase in the AUC of anesthesia for proliposomal ropivacaine compared with plain ropivacaine (mean difference, 1010; 95% confidence interval [CI], 625-1396 g[middle dot]h/mm2; P 2 years) at room temperature. (C) 2016 International Anesthesia Research Society
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Cricoid and left bronchial diameter in the pediatric population
Summary
Background
Lung isolation in the pediatric population can be problematic. The diameter and length of the right and left mainstem bronchi are not well described in young children. Information regarding these measurements may help determine the appropriate size of endotracheal tubes for endobronchial intubation as well as the development of lung isolation devices for the pediatric population. The present study is based on computed tomography (CT) measurements to evaluate airway dimensions. The goal of this study was to define the relationship between the diameters of the left mainstem bronchus (LMSB) and the cricoid ring, and to study the effect of age, weight, and height on these dimensions.
Methods
The two-dimensional CT images of 102 children, ranging in age from 1 month to 10 years, undergoing radiological evaluation unrelated to airway symptomatology were examined. The cricoid dimensions (anteroposterior and transverse diameters) were measured using transverse plane images. The LMSB diameter was measured below the carina along the long axis of left main bronchus. Univariate regression analysis was used to determine whether one or more of the variables (age, gender, height, weight) had a predictable relationship with the cricoid and the LMSB diameters.
Results
The cricoid as well as the LMSB diameters increase with age, height, and weight. The relationship between the cricoid diameter and the LMSB diameter remains constant across all ages with a ratio of 0.78 ± 0.14. This ratio was slightly larger for girls than boys (0.81 ± 0.16 vs 0.77 ± 0.13).
Conclusion
The cricoid to LMSB ratio (relationship) remains constant with respect to age, height, and weight.
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