Nuclear Medicine

Distribution of bone tracer uptake in symptomatic knees after ACL reconstruction compared to asymptomatic non-operated knees: a method for better differentiating patient-specific from disease-specific bone tracer uptake in SPECT/CT Abstract Objective To evaluate the differences of bone tracer uptake (BTU) in symptomatic and asymptomatic contralateral knees in patients after reconstruction of the anterior cruciate ligament (ACL-R) and to identify typical BTU patterns and threshold values to differentiate pathological from physiological BTU. Methods 53 patients after unilateral ACL-R were retrospectively included in the study. The population was subdivided into a group of symptomatic operated knees and a group of contralateral asymptomatic non-operated knees. BTU was measured in SPECT/CT using a validated anatomical localization-scheme and normalized mean BTU values were calculated in both knees. Wilcoxon signed rank-test and Pearson's rank-correlation coefficient were used (p < 0.05). Results Symptomatic knees after ACL-R showed significantly more BTU than asymptomatic ones (p < 0.01).Based on the measured BTU activity in SPECT/CT in symptomatic operated and asymptomatic non-operated knees, intensity thresholds of pathological BTU were established. A BTU threshold of greater than the Median + 1 SD of the asymptomatic non-operated knee was defined as pathological. In both groups the highest mean BTU was found on the femoral, tibial and patellar articular surfaces, the lowest BTU in femoral and tibial regions far from the joint. Conclusions The established BTU thresholds for SPECT/CT in knees after ACL-R help to differentiate disease-specific from patient-specific BTU. It could be speculated that BTU in asymptomatic knees equates to the preoperative condition of the knee joint before ACL-R. Therefore, the results of this study help to understand in-vivo loading of the knee and ultimately lead to prediction of development of osteoarthritis in an early stage.

18 F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma Abstract Objective The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4‑dihydroxy‑6‑[18F]‑fluoro-l‑phenylalanine (F-DOPA) uptake parameters with IDHmutation, 1p/19q status, and survival outcomes in patients with glioma. Methods The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13 years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDHmutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan–Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. Results There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5 months (range 3.5–74 months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. Conclusions F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

Fundamental study of radiogallium-labeled aspartic acid peptides introducing octreotate derivatives Abstract Objective Somatostatin receptors are highly expressed in neuroendocrine tumors, and many radiolabeled somatostatin analogs for diagnosis and treatment have been developed. To simultaneously detect not only primary cancer but also bone metastases, this study aimed to develop a positron emission tomography probe using generator-produced nuclide Gallium-68 (T1/2 = 68 min), in which a carrier for primary cancer, a carrier for bone metastases lesions, and a stable gallium complex are introduced into the one molecule. Based on this strategy, the somatostatin receptor-targeted peptide, [Tyr3]-octreotate (TATE), aspartic acid peptide (Dn) with high binding affinity for hydroxyapatite, and Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a stable gallium complex were selected. The novel complexes, Ga-DOTA-Dn-TATE (n = 0, 2, 5, 8, or 11), were designed, synthesized, and evaluated. The radiogallium complexes were prepared using the easy-to-handle radioisotope 67Ga due to relatively long half-life. Methods The radiogallium complex precursor DOTA-Dn-TATE was synthesized by the Fmoc-based solid-phase method and by the air oxidation method to form the disulfide bond. [67Ga]Ga-DOTA-Dn-TATE was synthesized by reacting DOTA-Dn-TATE and 67Ga. Hydroxyapatite binding assays, in vitro cellular uptake experiments in AR42J tumor cells, in biodistribution experiments in AR42J tumor-bearing mice, were performed using [67Ga]Ga-DOTA-Dn-TATE. Results The radiochemical purities of [67Ga]Ga-DOTA-Dn-TATE were > 96.0%. In in vitro and in vivo experiments, [67Ga]Ga-DOTA-D11-TATE had a high affinity for hydroxyapatite and highly accumulated in bone. However, the uptake of [67Ga]Ga-DOTA-D11-TATE into somatostatin receptor-positive AR42J cells was lower than that of [67Ga]Ga-DOTA-TATE, and the accumulation of [67Ga]Ga-DOTA-D11-TATE in tumor was significantly low. Conclusion Ga-DOTA-D11-TATE may not be recognized by somatostatin receptor by the introduction of D11, and the charge adjustment may be important for somatostatin receptor-positive cell uptake.

Brain 18 F-FDG distribution: which region is most affected by increased plasma glucose levels?

Clinical feasibility of early scanning after administration of 68 Ga-DOTATOC Abstract Objective Positron emission tomography (PET)/computed tomography (CT) using 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) is usually performed about 1-h post-injection; however, because of rapid blood clearance, the waiting time for scanning could possibly be shortened without affecting diagnostic performance. The purpose of this study was to investigate the feasibility of early scanning at 30 min post-injection. Methods Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min and 60-min post-injection. The number of known or suspected pathological lesions, and quantitative values of those lesions and physiological uptake were compared. SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were calculated as quantitative values of the pathological lesions. Results A total of 125 known or suspected pathological lesions were found at both timepoints, with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU were highly reproducible, with Spearman's ρ of 0.983, 0.986, 0.918, and 0.981, respectively. The average percent differences (%DIFFave) defined as the differences of the values divided by the value at 1-h post-injection were 11.1% for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological uptake in the two datasets was closely comparable in the pituitary gland (Spearman's ρ = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970, 6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%). Conclusion The diagnostic performance of visual interpretation should be comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post-injection. Some differences between quantitative values may exist; however, they appear to be minimal.

Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review Abstract To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.

The significant value of predicting prognosis in patients with colorectal cancer using 18 F-FDG PET metabolic parameters of primary tumors and hematological parameters Abstract Objects The purpose was to evaluate the correlation of the pre-treatment hematological parameters with metabolic parameters of primary tumor in baseline 18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the prognostic value of both. Methods We retrospectively investigated 231 patients with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested in the same term. PET parameters in term of hematological parameters and pathological characteristics of primary tumor were compared. Kaplan–Meier survival analysis was performed in the patients without distant metastasis. The differences of disease-free survival between groups were compared by log-rank tests. Results Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were significantly correlated with all the metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV (24.82 ± 18.16 vs 19.06 ± 13.30, P = 0.039) and TLG (219.04 ± 186.94 vs 166.45 ± 146.39, P = 0.047) than those whose NLR ≤ 3. NLR in those patients with distant metastasis was significantly higher than those without distant metastasis (P = 0.018) while LMR in those patients with distant metastasis was significantly lower than those without distant metastasis (P = 0.032). Survival analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008) and high LMR (P = 0.027) revealed significant survival benefit. Conclusions There was a significant association between the pre-treatment hematological parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients with CRC. It might be helpful in those patients with high NLR and low LMR to undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.

Comparison of 18 F-Choline PET/CT and MRI functional parameters in prostate cancer Abstract Aim 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. Materials and methods Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. Results The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). Conclusions No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis Abstract Objective To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed. Methods This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT and clinical follow-up. The image data were reconstructed with CT attenuation correction and scatter correction, and with only CT attenuation correction (CTAC). The new method extracted striatal VOI according to the high-level counts and the average striatum volume, and calculated SBR using the reference occipital counts. The SBR values for each patient were obtained using the Tossici-Bolt method (SBRBolt) and our method. Reproducibility of SBR calculation using our method was compared by two operators. Results The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBRBolt (p < 0.001), except for the CTAC images. There were no differences in SBR between the two operators using our method. The diagnostic accuracies with our method for the PS and DLB groups were 98.4 and 96.0%, respectively. Conclusion Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions Abstract Objective To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. Methods 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA. Results 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/Gratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. Conclusions 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.

Dental Research

Load-deflection characteristics of coated and noncoated nickel-titanium wires in self-ligating brackets using a modified bending test: An in vitro study Tripti Tikku, Rohit Khanna, Akhil Agarwal, Kamna Srivastava, Shashank Shekhar, Ivy Shukla Dental Research Journal 2019 16(1):1-6 Background: To determine and compare the force-deflection values of different types of nickel-titanium (NiTi) wires during unloading phase at varying deflections, that is 1 mm, 1.5 mm, 2 mm, and 2.5 mm, with the use of self-ligating ceramic brackets using modified bending test on a typodont under controlled temperature conditions. Materials and Methods: In this in vitro study total of 45 wires of ovoid shape of three different NiTi wires – pseudoelastic NiTi (Group I), heat activated NiTi (Group II), and esthetic coated NiTi (Group III) for maxillary arch were tested after insertion in ceramic self-ligating brackets bonded to plastic teeth of phantom jaw . The maxillary left lateral incisor was removed to simulate a malpositioned tooth which acted as the load site, and load-deflection characteristics were measured during unloading using Instron, and data analyzed statically by two-way analysis of variance ,Tukey's post hoc test, intraclass correlation coefficient and Pearson correlation coefficient. A two-sided (α = 2) P < 0.05 was considered statistically significant. Results: When wires were compared at each deflection statistically significant difference was observed between the three groups of wires (Group I > Group II > Group III) at all the four levels of deflection except for Group II versus Group III at 1 mm, 1.5 mm, and 2 mm of deflection. Statistically significant difference was noted in mean load values for comparisons made at different deflections for each wire except for the comparison made at 1.5 versus 2 mm for Group II and Group III. Conclusion: Overall comparison showed esthetic coated Ni-Ti wires gave significantly lower mean load values, followed by heat activated and pseudoelastic NiTi wires. Thus, heat activated NiTi wires are best suited in patients with severe malpositions/periodontitis, while for esthetically conscious patients esthetic coated NiTi can be used.

Effects of menthol-flavored substances at the cellular level on oral mucosal sites Nanda Prasad, Sarvesh Vijay, A Yashwanth Reddy, S Nonitha Dental Research Journal 2019 16(1):7-11 Background: The purpose of this study was to determine the effects of menthol-flavored substances at the cellular level in different mucosal sites of the oral cavity and to compare the cellular changes between individuals without the habit of chewing menthol-flavored substances and individuals with the habit. Materials and Methods: This was an experimental cytology study including a total of 500 individuals belonging to the age group of 18–45 years based on the inclusion or exclusion criteria. The selected participants were divided into two groups of 250 participants each, based on participants not having the habit of chewing menthol-flavored substances (Group I) and participants having the habit of chewing menthol-flavored substances (Group II). Cytological smears were taken by gently scraping the mucosal surfaces in different sites of the oral mucosa using a wooden spatula and stained with Papanicolaou, analyzed under microscope for any cellular changes. The results were tabulated and statistically analyzed using Chi-square test and Fisher's exact test. P < 0.05 was considered statistically significant. Results: Micronuclei seen in all the participants belonging to group with the habit of chewing menthol-flavored substances with a P < 0.001 which was considered highly significant. Alteration in the nuclear-cytoplasmic ratio was also seen P = 0.001, which showed significant at 1% significance level. Conclusion: Participants with habit of chewing menthol-flavored substances showed the presence of micronuclei and slight alteration in the nuclear-cytoplasmic ratio, which could be directly related to genotoxicity and cell damage.

Impact of occupational dental erosion on oral health-related quality of life among battery factory workers in Bengaluru, India Amit Kumar, Manjunath P Puranik, KR Sowmya, Soni Rajput Dental Research Journal 2019 16(1):12-17 Background: A greater understanding of impact of occupational dental erosion on oral health-related quality of life (OHRQoL) will sensitize both employee and employers to adopt strict protective measures for oral health. The research aimed to determine the relationship between occupational dental erosion and OHRQoL among battery and other factory workers in Bengaluru, India. Materials and Methods: This cross-sectional comparative study enrolled a total of 400 workers. Structured proforma assessed information on sociodemographic details, oral hygiene practices, adverse oral habits, and work-related practices. OHRQoL was determined using oral health impact profile-14 (OHIP-14). Dental erosion was measured using Smith and Knight's tooth wear index modified by Millward et al. 1994 scoring system independent t-test, Mann–Whitney U-test and Spearman's correlation was performed. P < 0.05 was considered statistically significant. Results: The mean age of the participants in the study and control groups was 43.11 ± 8.02 and 45.93 ± 6.16 years, respectively. Less than half of the participants in the study group had positive behavioral work practice. The prevalence and severity of dental erosion was significantly higher in study group (39.5%) than control group (11.5%). Mean OHIP-14 score was significantly lower in study group (23.88 ± 0.88) than control group (26.06 ± 9.67). Dental erosion significantly correlated with work experience and OHIP-14. Conclusion: The findings highlight the impact of occupational dental erosion on OHRQoL. Measures to enhance occupational safety thereby reducing exposure to occupational hazards are needed.

Comparative investigation of primary stability of four different dental implants in low-density bone model Saied Nokar, Amirali Reza Rasouli-Ghahroudi, Elham Shidvash, Faezeh Atri Dental Research Journal 2019 16(1):18-23 Background: Primary stability is one of the prerequisites of immediate loading. The aim of this study was to compare the primary stability of four different implant systems in low-density bone models. Materials and Methods: In this in vitro experimental study, 20 fixtures from four implant body designs were selected: Zimmer Tapered Screw-Vent (ZTSV), NobleReplace Tapered (NRT), Replace Select Tapered (RST), and Dentium SuperLine (DSL). Fixtures were inserted in low-density bone models according to manufacturer drilling protocol by one surgeon. Measurement of insertion torque value (ITV), resonance frequency analysis (implant stability quotient [ISQ]), and reverse torque value (RTV) was recorded for each fixture. The data were analyzed with one-way ANOVA and post hoc tests (Tukey honestly significant difference) (P < 0.05). Results: ZTSV had significantly lower amount of insertion torque in comparison to other systems (P = 0.045). RTV was significantly lower in ZTSV in comparison to DSL and NRT (P = 0.004). ISQ value in NRT (ISQ = 67) was significantly higher than other systems (P = 0.000). The lowest amount of ISQ was in RST system (ISQ = 53) with significant difference (P = 0.000). Conclusion: This study demonstrated that primary stability of different implant systems was not comparable and implant design was effective on ITV, RTV, and ISQ.

Assessment of antimicrobial activity of different concentrations of Tinospora cordifolia against Streptococcus mutans: An in vitro study Sankalp Agarwal, Priyadarshini H Ramamurthy, Bennete Fernandes, Avita Rath, Preena Sidhu Dental Research Journal 2019 16(1):24-28 Background: The antimicrobial property of Tinospora cordifolia has been tested against a variety of microorganisms in the literature. The present study aimed to assess the antimicrobial activity of different concentrations of commercially available T. cordifolia powder against Streptococcus mutans. Materials and Methods: An in vitro study was undertaken in which extract of T. cordifolia was obtained using 100% ethanol by maceration. Seven different concentrations were prepared and tested against S. mutans in brain–heart infusion agar medium. Plates were incubated aerobically at 37°C for 48 h, and zone of inhibition was measured using Vernier caliper. 0.2% chlorhexidine and dimethylformamide were used as positive and negative controls respectively. The data were analysed by descriptive analytic tests. Results: The maximum antibacterial activity of T. cordifolia was observed with a volume of 40 μl at 2% concentration with a zone of inhibition of 19 mm. A 30 μl volume of 0.2% chlorhexidine showed a zone of inhibition of 28 mm, and no zone of inhibition was observed with dimethylformamide. Conclusion: Tinospora exhibited antimicrobial activity against S. mutans. However, it needs to be confirmed further with in vivo studies.

Association between quality of sleep and chronic periodontitis: A case–control study in Malaysian population Vijendra Pal Singh, Joe Yin Gan, Wei Ling Liew, Htoo Htoo Kyaw Soe, Sowmya Nettem, Sunil Kumar Nettemu Dental Research Journal 2019 16(1):29-35 Background: Periodontitis is a public health concern since it is a major factor in tooth loss worldwide and has association with many systemic diseases. Sleep is a complex and essentially biological process and a critical factor for maintaining mental and physical health. Since inflammation is characteristic of both chronic periodontitis and sleep deprivation, few studies in recent years present the contradictory results regarding this potential association. The objective of the present study was to investigate the association between quality of sleep and chronic periodontitis. Materials and Methods: A total of 200 individuals participated in this study. All participants underwent a comprehensive clinical periodontal examination. Case–control were identified using the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions for periodontal disease. The quality of sleep was assessed by Pittsburgh Sleep Quality Index. The univariate and multivariate logistic regression analysis was used to test the influence of variables (quality of sleep, age, sex, ethnicity, education, and socioeconomic status), in the occurrence of periodontitis. Odds ratio (OR) and respective confidence intervals (CIs) were calculated and reported. P ≤0.05 was considered statistically significant. Results: The prevalence of poor quality of sleep was 56.75% in cases (periodontitis group) and 43.24% in control group. There was positive association between quality of sleep and chronic periodontitis (OR = 3.04; 95% CI = 1.42–6.5; P = 0.004). In multivariate logistic regression analysis, only the age was significantly related to the periodontitis (OR = 1.11; 95% CI = 1.07–1.41; P < 0.001), other variables failed to reach the significant level. Conclusion: Poor quality of sleep was significantly associated with chronic periodontitis. Only the age was significantly related to periodontitis among the other covariable measured.

Sealants revisited: An efficacy battle between the two major types of sealants – A randomized controlled clinical trial B Prathibha, P Parthasarthi Reddy, Md Shakeel Anjum, M Monica, BH Praveen Dental Research Journal 2019 16(1):36-41 Background: The aim of this study is comparing the retention and caries preventive effect of the glass-ionomer fissure sealant and resin-based fissure sealant. Materials and Methods: A randomized-controlled split-mouth study was conducted to compare the retention and the caries preventive effect of light-cured resin-based sealant (3M ESPE) and glass ionomer sealant (Fuji VII). The sealants were applied to either the right or the left lower mandibular molars (7-9 yrs of age) in 120 school children, based on the randomization process. They were recalled for assessment of clinical retention at intervals of 3, 6, and 12 months. The caries-preventive effect between the two materials was tested statistically by the McNemar's test for matched pairs, and the differences observed with regard to the retention of the materials was tested by Chi-square tests. The level of significance was set to be at P < 0.05. Results: At the end of 12th month, sealant retention is found to be higher in the resin-based sealant group compared to the glass ionomer group. In the glass ionomer sealants placed, 101 (91%) were caries-free and 10 (9%) had caries. In the resin-based sealant, 105 (94.60%) had sound teeth and 6 (5.4%) had dental caries (P = 0.34). Conclusion: The glass ionomer sealant was less retentive when compared to resin sealants. The caries incidence between the glass ionomer and resin-based sealants was not statistically significant.

A comparative study of the clinical efficiency of chemomechanical caries removal using Carie-Care gel for permanent teeth of children of age group of 12–15 years with that of conventional drilling method: A randomized controlled trial Priyanka Sontakke, Prateek Jain, Aniket Dhote Patil, Gautam Biswas, Pramod Yadav, Diljot Kaur Makkar, Vikas Jeph, Banu Pyari Sakina Dental Research Journal 2019 16(1):42-46 Background: Dental caries is considered as one of the most serious dental diseases that results in localized dissolution and destruction of the calcified tooth tissues. As possible alternatives to conventional techniques of caries removal, chemomechanical caries removal systems have emerged. This study aims to clinically observe the advantages of chemomechanical method of caries removal over conventional technique. Materials and Methods: Inthis randomized controlled trial a total of 60 children with Class 1 open carious lesions were selected for the study. They were divided into two equal groups according to a method of caries removal (30 chemomechanical and 30 conventional on permanent molars). In Group A, caries was removed using the Carie-Care system and in Group B with the conventional drill and were restored equally with glass ionomer cement. The visual analogy face scale was used to determine the level of anxiety in children at baseline, during treatment and after treatment. Results: The results were subjected to statistical analysis using Student's unpaired t-test. It showed that though chemomechanical technique took a marginal increase in time compared to the conventional technique, it was found to be more comfortable for all the children. Conclusion: Chemomechanical technique though time-consuming is definitely superior compared to the conventional technique provided we use a less technique sensitive restorative material which retains in the oral cavity for longer period. It is definitely a better treatment protocol in school-based dental treatment and atraumatic restorative dentistry compared to the conventional technique.

The effect of office bleaching on the color and bond strength of resin restorations Homayoon Alaghehmand, Marzieh Rohaninasab, Ali Bijani Dental Research Journal 2019 16(1):47-52 Background: Bleaching may affect the bond strength of existing composite fillings and may weaken it. Hence, the aim of this study was to find the best method of in-office bleaching with the least effect on microshear bond strength (MSBS) of existing composite resin fillings to tooth structure. Materials and Methods: In this in vitro study, Class V cavities were prepared on buccal surface of 50 extracted third human sound molars. The cavities in 25 teeth had enamel axial walls, Group E, which were divided into five subgroups of E1 through E5 and in 25 teeth had dentin axial walls, Group D, which were divided into five subgroups of D1 through D5. Cavities were treated with Single Bond 2 adhesive system and restored with composite resin (Z250). The corresponding subgroups received similar bleaching methods and materials; 1 – not bleached, 2 – hydrogen peroxide (HP) 25%, 3 – HP + ultraviolet light, 4 – HP + light-emitting diode-curing device, and 5 – HP + diode laser. Teeth colors were monitored before and after bleaching, and MSBS test and failure modes were examined. Results were analyzed with one-way ANOVA and Kruskal–Wallis tests. P < 0.05 was considered significant. Results: One-way ANOVA did not show differences in MSBS of enamel subgroups but showed significant differences in dentin subgroups (P < 0.00). Adhesive fracture in all of the subgroups was the most frequent mode of failure. Kruskal–Wallis test showed that laser was the most effective instrument to change ΔE. Conclusion: Diode laser was the best method for tooth bleaching because lowering the shear bond strength between composite resin and enamel was minimum and also had the most ΔE in tooth bleaching.

In vitro evaluation of coronal discoloration following the application of calcium-enriched mixture cement, Biodentine, and mineral trioxide aggregate in endodontically treated teeth Solmaz Araghi, Atefeh Khavid, Mostafa Godiny, Mahshid Saeidipour Dental Research Journal 2019 16(1):53-59 Background: This study sought to assess and compare coronal discoloration following the application of white mineral trioxide aggregate, Biodentine, and calcium-enriched mixture cement in endodontically treated teeth. Materials and Methods: In this in vitro experimental study, 64 freshly extracted sound human premolars were selected, cleaned, and stored in saline. After cleaning, shaping, and obturation the root canal of the teeth, the teeth were randomly assigned to one control (n = 4) and three experimental (n = 20) groups. In the experimental groups, the cement were applied over the canal orifices in 3-mm thickness. All teeth were then restored with composite resin. Color parameters, according to the CIE L*a*b* system, were measured using Vita Easyshade spectrophotometer before application of cement and at 1 week, 1 month, 2 months, and 3 months after the application of cement. The recorded values were statistically analyzed using descriptive and analytical statistics. For analytical statistics, Kolmogorov–Smirnov test was applied to assess normal distribution of data. ANOVA was used to compare the results at baseline and repeated measures. P < 0.05 was considered statistically significant Results: Significant differences were noted in color change (ΔE) between all time points except between ΔE4 (2 months) and ΔE5 (3 months) (P < 0.01). However, tooth discoloration caused by the three cement was not significantly different (P = 0.343). Conclusion: The three tested cement were not significantly different in terms of causing coronal discoloration in endodontically treated teeth.

High Prevalence of Plasmid-Mediated Quinolone Resistance Determinants Among Serotype K1 Hypervirulent Klebsiella pneumoniae Isolates in China

Microbial Drug Resistance, Ahead of Print.


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Hidden Carbapenem Resistance in OXA-48 and Extended-Spectrum β-Lactamase-Positive Escherichia coli

Microbial Drug Resistance, Ahead of Print.


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Unexplored Genetic Diversity of Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii Isolates from Tertiary Hospitals in Honduras

Microbial Drug Resistance, Ahead of Print.


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Exposure to Sublethal Concentrations of Benzalkonium Chloride Induces Antimicrobial Resistance and Cellular Changes in Klebsiellae pneumoniae Clinical Isolates

Microbial Drug Resistance, Ahead of Print.


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Screening of mecI Gene in Staphylococcus Strains Isolated in Transylvania Region of Romania

Microbial Drug Resistance, Ahead of Print.


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Disinfectant Resistance Profiles and Biofilm Formation Capacity of Escherichia coli Isolated from Retail Chicken

Microbial Drug Resistance, Ahead of Print.


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High Level of Conservation of Mitochondrial RNA Editing Sites Among Four Populus Species

RNA editing occurs in the endosymbiont organelles of higher plants as C-to-U conversions of defined nucleotides. The availability of large quantities of RNA sequencing data makes it possible to identify RNA editing sites and to quantify their editing extent. We have investigated RNA editing in 34 protein-coding mitochondrial transcripts of four Populus species, a genus noteworthy for its remarkably small number of RNA editing sites compared to other angiosperms. 27 of these transcripts were subject to RNA editing in at least one species. In total, 355 RNA editing sites were identified with high confidence, their editing extents ranging from 10 to 100%. The most heavily edited transcripts were ccmC with the highest density of RNA editing sites (50.5 sites / kb) and ccmFn with the highest number of sites (39 sites). Most of the editing events are at position 1 or 2 of the codons, usually altering the encoded amino acid, and are highly conserved among the species, also with regard to their editing extent. However, one SNP was found in the newly sequenced and annotated mitochondrial genome of P. alba resulting in the loss of an RNA editing site compared to P. tremula and P. davidiana. This SNP causes a C-to-T transition and an amino acid exchange from Ser to Phe, highlighting the widely discussed role of RNA editing in compensating mutations.

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6 lifesaving seat belt tips for EMTs and paramedics

Whether you're treating a minor cut or a MCI, there's no excuse for not using proper restraint while riding in an ambulance.

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Polish pioneers of local anaesthesia

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What does surgery owe to anaesthesia?

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The genesis of anaesthesia in prehistory

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My own experience in performing ether anaesthesia

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The influence of propofol on middle cerebral artery flow velocity (VMCA) in patients with unruptured intracranial aneurysms during induction of general anaesthesia

Background: The estimated prevalence of unruptured intracranial aneurysms is 3%. Standard monitoring does not enable one to assess the influence of anaesthetics on the factors determining intracranial homeostasis. Thanks to transcranial Doppler ultrasonography, middle cerebral artery flow velocity (VMCA), reflecting cerebral blood flow, can be measured. The aim of the study was to assess the effects of propofol on intracranial homeostasis in patients with unruptured intracranial aneurysms during the induction of anaesthesia based on VMCA changes. Methods: The study encompassed 21 patients (group II) anaesthetised for elective craniotomy due to unruptured intracranial aneurysms. The control group (group I) included 21 patients who underwent discoidectomy. VMCA, as well as HR, MAP, etCO₂, and SpO₂ were monitored at the following time points: T0 — onset of study; T1 — after 1 minute; T2 — onset of preoxygenation; T3 — after 1 minute of preoxygenation; T4 — administration of fentanyl; T5 — 1 minute after fentanyl; T6 — administration of propofol; T7 — 1 minute after propofol; T8 — intubation; T9 — 1 minute after intubation; T10 — 2 minutes after intubation. Results: In both groups, no changes in mean HR, etCO₂ and SpO₂ were observed at the successive time points of observation. In groups I and II, an MAP decrease between T6 and T7 and an MAP increase between T7 and T9 were noted. There were no intergroup differences in mean values of MAP at the times of observation. In both groups and bilaterally, a VMCA decrease was recorded between T6 and T7 and an increase between T7 and T8. There were no intergroup differences in mean values of VMCA at the times of observation. In both groups, a weak correlation between VMCA and MAP changes was found bilaterally. Conclusions: Propofol depresses the cerebral circulation during the induction of anaesthesia. The presence of an unruptured aneurysm does not affect the reactivity of the cerebral vessels during the induction of anaesthesia with propofol.

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The role of anaesthesiology and intensive care for patient safety in the perioperative period: past, present and future

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Regional anaesthesia induced peripheral nerve injury

Regional anaesthesia techniques have gained great popularity in recent years, as it provides excellent anaesthesia and analgesia for many surgical procedures. Lots of courses, workshops, multimedia materials and wide access to high-end ultrasound devices make the Polish anaesthesiologists perform various blockades with enthusiasm. But there is also a dark side of regional anaesthesia, which should not be forgotten — complications. Although nerve injuries are considered to be multifactorial in nature and the vast majority of them are not due to regional anaesthesia, anaesthesiologists and anaesthetised patients must be aware of the risk. Because of the potentially devastating sequelae of regional blocks, updating knowledge on this topic is very needed. The aim of this review is to summarize current knowledge concerning regional anaesthesia induced peripheral nerve injury.

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Effect of dexmedetomidine or propofol sedation on haemodynamic stability of patients after thoracic surgery

Background: Dexmedetomidine and propofol are commonly used sedative agents in non-invasive ventilation as they allow for easy arousal and are relatively well controllable. Moreover dexmedetomidine is associated with low risk of respiratory depression. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the influence of both drugs on hemodynamic effects in patients after thoracic surgical procedures receiving dexmedetomidine or propofol for noninvasive postoperative ventilation. Methods: A prospective, randomised, observational study University Hospital. Interventions: Continuous sedation with dexmedetomidine or propofol for six hours of postoperative non-invasive ventilation after thoracic surgery, with concomitant use of continuous epidural analgesia. Results: A total of 38 patients (20 dexmedetomidine and 18 propofol) were included in the analysis. The primary outcomes of this study is that heart rate, systolic and mean arterial blood pressure did not differ significantly between the groups, but diastolic arterial blood pressure was significantly higher in propofol group. Comparison analysis of epinephrine usage did not reveal significant differences between the groups. Cardiac output (CO) and cardiac index (CI) analysis did not show significant differences between the groups, but there is a clear tendency of lower values of CO/CI in group receiving propofol. We also observed similar tendency in stroke volume index (SVI) and stroke volume variation (SVV) values, but also those differences did not reach statistical significance. Systemic vascular resistance index (SVRI) values were higher in propofol group, exceeding reference values, but similarly, the difference between the groups was not significant. Conclusions: The main finding of this study is that dexmedetomidine and propofol provide similar advantages in haemodynamic stability during short-term sedation for non-invasive ventilation after thoracic surgical procedures in patients receiving continuous epidural analgesia.

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The successful treatment of hepatocellular carcinoma arising from congenital hepatic fibrosis using radiofrequency ablation under laparoscopy

Abstract

Congenital hepatic fibrosis (CHF), a fibropolycystic disease, is characterized by bile duct malformation, periportal fibrosis, and renal polycystic disease. Although cholangiocellular carcinoma is the primary tumor arising from fibropolycystic diseases, hepatocellular carcinoma (HCC) is extremely rare. In addition, no algorism for determining the optimum HCC treatment has yet been available in cases of fibropolycystic disease due to variations in the background liver and renal conditions. We herein report a patient with HCC arising from CHF that was successfully treated using radiofrequency ablation (RFA) under laparoscopic assistance. A 37-year-old man with CHF was admitted to our hospital for treatment of HCC in 2014. Imaging revealed HCC located in hepatic segments II and VIII with diameters of 28 and 24 mm, respectively. There had been no histories of recurrent cholangitis or renal failure after when CHF was diagnosed in 2003. In addition, esophageal varices were well controlled. We achieved sufficient ablation using a bipolar ablation system without any complications. The post-operative course was uneventful, and the patient was free from HCC for 4 years. Thus, locoregional therapy, including RFA, is acceptable for the treatment of HCC arising from CHF when the background liver and kidney are preserved.

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Self-Loosening Characteristics of Three-Dimensional Printed Bolted Joints

3D Printing and Additive Manufacturing, Ahead of Print.


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Utilization of arterial pulse waveform analysis during non-cardiac surgery in Japan: a retrospective observational study using a nationwide claims database

Abstract

Arterial pulse waveform analysis (APWA) is used for cardiac output monitoring. However, data on the frequency of and patient characteristics for specialized pressure transducer for APWA (S-APWA) use are lacking. We retrospectively identified 175,201 patients aged 18 years or older, who underwent non-cardiac surgery under general anesthesia with an arterial catheter from January 1, 2014, to December 31, 2016. We extracted data on patient demographics, comorbidities, surgical and anesthesia characteristics, and hospital characteristics. Among the full study cohort, 24,605 (14.0%) patients were monitored using S-APWA. Further, the use of S-APWA was higher in patients undergoing high-risk surgery than in those undergoing low-risk surgery [high vs low: adjusted odds ratio (aOR) 1.95; 95% confidence interval (CI) 1.76–2.15, moderate vs low: aOR 1.11; 95% CI 1.01–1.22] and those with more comorbidities than in those with less comorbidities (high vs low: aOR 1.49; 95% CI 1.42–1.56, moderate vs low: aOR 1.25; 95% CI 1.20–1.31). S-APWA use was significantly associated with both surgery risk and patients' comorbidities. In conclusion, our study may provide a benchmark for future studies related to the appropriate use of S-APWA.

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Leveraging Public Health Research to Inform State Legislative Policy that Promotes Health for Children and Families

Abstract

Purpose Engagement in policy is an essential public health service, with state legislatures serving as important arenas for activity on issues affecting children and families. However, a gap in communication often exists between policymakers and public health researchers who have the research knowledge to inform policy issues. We describe one tool for researchers to better leverage public health research to inform state legislative policymaking on issues of relevance to children and families. Description The Oregon Family Impact Seminar (OFIS), adapted from the Policy Institute for Family Impact Seminars, applies a systematic process to bring a synthesis of research findings on public health issues to state legislators using a six-step process: (1) identify candidate topics, (2) recruit legislative champions, (3) select the topic, (4) identify and prepare speakers, (5) host the presentations, and (6) develop and disseminate a research brief as a follow-up contact. Assessment Use of this model in Oregon has produced policy impact; for example, the 2015 presentation, "Two-Generation Approaches to Reduce Poverty," prompted ongoing dialogue culminating in a new statute to increase Earned Income Tax Credit for parents with young children. This approach also has strengthened relationships among researchers and legislators, which serves to streamline the OFIS process. Conclusion This model is an effective vehicle for leveraging public health research findings to inform state-level policy. This model also serves to connect researchers with opportunities to engage with policymakers to address significant public health problems, particularly those addressing social, economic, and environmental determinants of health for children and families.

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Associations Between Maternal Exposure to Child Abuse, Preterm Birth, and Very Preterm Birth in Young, Nulliparous Women

Abstract

Objectives Preterm birth (PTB) is a leading cause of infant morbidity and mortality. One goal of Healthy People 2020 is to understand the role of preconception lifecourse exposures in relation to pregnancy outcomes, including PTB. The objective of this study was to examine the relationship between maternal exposure to multiple forms of childhood abuse and PTB and very preterm birth (vPTB), utilizing a national, population-based sample. MethodsThis study utilized retrospective self-reported maternal exposure to parent/adult caregiver perpetrated emotional, physical, and sexual abuse; non-parental/adult caregiver perpetrated sexual abuse; and history of PTB and vPTB in the National Longitudinal Study of Adolescent to Adult Health. The cross-sectional analytic study population consisted of first deliveries to 4181 nulliparous women (mean age at time of delivery = 21.7 years). Results With one exception, we did not observe associations between experiences of child abuse and the likelihood of PTB or vPTB. Only sexual abuse, accompanied by physical force and perpetrated by a non-parent/adult caregiver, was associated with an increased odds of vPTB (aOR = 1.94 (95% CI 1.10, 3.44)), particularly in women for whom abuse began after age 9 (aOR = 2.32 (95% CI 1.25, 4.28)).Conclusions for Practice The relationship between maternal exposure to child abuse and PTB may be limited to specific abuse and PTB subtypes, namely non-parent/caregiver perpetrated sexual abuse by force and vPTB. Future studies should also examine possible effect modifiers, such as maternal age and resilience, which may have the potential to inform interventions that can mitigate effects of maternal early life adversity.

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Dynamic balance and instrumented gait variables are independent predictors of falls following stroke

Falls are common following stroke and are frequently related to deficits in balance and mobility. This study aimed to investigate the predictive strength of gait and balance variables for evaluating post-strok...

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Stimulation of paralysed quadriceps muscles with sequentially and spatially distributed electrodes during dynamic knee extension

During functional electrical stimulation (FES) tasks with able-bodied (AB) participants, spatially distributed sequential stimulation (SDSS) has demonstrated substantial improvements in power output and fatigu...

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Gait variability following abrupt removal of external stabilization decreases with practice in incomplete spinal cord injury but increases in non-impaired individuals

Individuals with incomplete spinal cord injury (iSCI) exhibit considerable lateral center of mass (COM) movement variability during gait transitions from a stabilizing to unassisted environment, while non-impa...

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Fixed muscle synergies and their potential to improve the intuitive control of myoelectric assistive technology for upper extremities

Users of myoelectric controlled assistive technology (AT) for upper extremities experience difficulties in controlling this technology in daily life, partly because the control is non-intuitive. Making the con...

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Simplified synchronous disconnection of pulmonary arteries and veins for right upper lobectomy

Abstract

Background

Video-assisted thoracoscopic lobectomy with lymphadenectomy is considered one of the most effective treatments for early non-small cell lung cancer. We developed a novel approach for lobectomy in patients with right upper lung cancer through simplified synchronous disconnection of pulmonary arteries and veins. This study aimed to evaluate the feasibility, efficacy, safety, and cost-effectiveness of this minimally invasive technique in managing right upper lobectomy.

Patients and methods

From March 2016 to September 2017, 62 patients with right upper lung cancer underwent lobectomy via simplified synchronous disconnection of pulmonary arteriovenous by video-assisted thoracoscopic surgery. All patients were followed up for 6–12 months after the procedure through clinic visits or telephone/e-mail interviews.

Results

Of the 62 patients (mean age, 57.2 ± 8.7 years), 28 were men (45.2%) and 34 (54.8%) were women. All procedures were successfully performed by thoracoscopy, with a mean operating time of 66.2 ± 9.0 min. The mean blood loss was 40.3 ± 19.5 mL. Only 1 (1.61%) patient required blood transfusion. The mean number of endoscopic linear stapling devices used was 2.6 ± 0.7. The mean number of lymph nodes harvested was 16.0 ± 1.6. Postoperative pneumonia was encountered in 4 (6.45%) patients. There was no postoperative mortality. The mean length of hospital stay was 5.3 ± 1.3 days. Six-month follow-up revealed an excellent clinical result and degree of satisfaction.

Conclusions

Simplified synchronous disconnection of pulmonary arteries and veins is a feasible, economical, safe, and effective therapeutic procedure for right upper lung carcinoma. This novel procedure shows promise as a viable surgical approach for right upper lobectomy.

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White paper: technology for surgical telementoring—SAGES Project 6 Technology Working Group

Abstract

Background

Recent advances in telecommunication technology and video conferencing systems have opened a new avenue for surgical instruction called "surgical telementoring." This report from the Technology Working Group of the SAGES Project 6 Summit reviews the telementoring technology that currently exists and proposes recommendations for minimum technology requirements and future technology development. While also providing insight in regulatory considerations, this review offers what prospective surgical telementoring participants need to know about the underlying technology with a specific focus on safety, reliability, transmission quality, ease of use, and cost.

Methods

Content experts from around the world, in minimally invasive surgery, surgical mentoring and telementoring, surgical education, business development, healthcare innovation, and regulation were invited to attend a 2-day summit in Los Angeles, USA to outline the current state of surgical telementoring and chart the challenges and opportunities going forward. This article summarizes the discussion, conclusions, and recommendation of the technology group with regard to telementoring technology.

Results

This article reviews the technical requirements which can be divided into the following categories: (1) safety, (2) reliability, (3) transmission quality, (4) ease of use, and (5) cost.

Conclusion

Telementoring applications are technology driven. Given the pace of change of technology, guiding principles in technology design and selection are warranted (Table 4). Telementoring technologies require two basic components, video capturing and display devices at the transmitting and receiving end, and a telecommunication link between them. Many additional features can be added to this basic setup including multiple cameras or video sources, remote camera zoom and pan, recording and storage of videos and images, and telestration capabilities to mention just a few. In general, the cost of these technologies is feature driven. The education framework for each specific application should determine the need for these features (Schlachta in Surg Endosc http://bit.ly/2TzxHIN).

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Operational effectiveness of three-dimensional flexible endoscopy: an ex vivo study using a new model

Abstract

Background and objectives

Two-dimensional (2D) images lack depth information and thus provide probabilistic recognition that do not completely match the actual three-dimensional (3D) information. Here, we investigated the operability of 3D endoscopes.

Methods

A 3D operation model was developed by passing 20 silk threads through upper and lower plates at 2-mm intervals in front and back rows separated by 1 mm. We evaluated accuracy and time of operating an electrosurgical knife. A successful operation was defined as pulling only a front-row thread; an unsuccessful operation was defined as pulling no thread (miss) or simultaneously pulling front- and back-row threads. Endoscopists (four experts, six trainees) repeated the operation under 2D and 3D conditions until individually accumulating 10 successful attempts under each condition.

Results

Operation accuracy was significantly higher for 3D compared with 2D in all endoscopists (88.5% vs. 61.3%; p < 0.01) and in both experience groups (trainees: 84.5% vs. 61.2%; experts: 95.2% vs. 61.5%; both p < 0.01). Operation time was significantly shorter for 3D compared with 2D in all endoscopists (12.5 ± 4.1 s vs. 14.8 ± 4.7 s; p < 0.01) and in both experience groups (trainees: 12.8 ± 4.2 s vs. 15.2 ± 4.9 s; experts: 12.1 ± 4.0 s vs. 14.3 ± 4.3 s; both p < 0.01).

Discussion

Compared with 2D endoscopy, 3D endoscopy significantly improved operation accuracy and shortened operation time, suggesting that 3D endoscopy enables accurate operation by depth information, aiding spatial recognition.

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Epidemiology and Whole-Genome Analysis of NDM-1-Producing Klebsiella pneumoniae KP3771 from Tunisia

Microbial Drug Resistance, Ahead of Print.


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Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Key points

In cold environment, mammals increase their feed intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown. Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation. Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance. Repression of mechanistic target of rapamycin (mTOR) signaling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signaling may be involved in the fasting‐induced cold resistance in fish. Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress.

Abstract

In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin), and nutritional approaches (fatty and acids amino diets) in wild or specific gene‐knock out zebrafish models (carnitine palmitoyltransferase‐1b deficient strain, CPT1b^−/− or autophagy‐related protein 12 deficient strain, ATG12^−/−), we verified that fasting‐stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance, from either physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signaling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.

This article is protected by copyright. All rights reserved

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Electrical amplification: KIR channels taking center stage in the hyperaemic debate

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Parkin overexpression protects from aging‐related loss of muscle mass and strength

Key points

Recent evidence suggests that impaired mitophagy, a process in charge of removing damaged/dysfunctional mitochondria and in part regulated by Parkin, could contribute to the aging‐related loss of muscle mass and function. Here, we show that parkin overexpression attenuates aging‐related loss of muscle mass and strength and unexpectedly causes hypertrophy in adult skeletal muscles. We also show that Parkin overexpression leads to increases in mitochondrial content and enzymatic activities. Finally, our results show that Parkin overexpression protects from aging‐related increases in markers of oxidative stress, fibrosis and apoptosis. Our findings place Parkin as a potential therapeutic target to attenuate sarcopenia and improve skeletal muscle health and performance. The aging‐related loss of muscle mass and strength, a process called sarcopenia, is one of the most deleterious hallmarks of aging. Solid experimental evidence indicates that mitochondrial dysfunctions accumulate with aging and are critical in the sarcopenic process. Recent findings suggest that mitophagy, the process in charge of the removal of damaged/dysfunctional mitochondria, is altered in aged muscle. Impaired mitophagy represents an attractive mechanism that could contribute to the accumulation of mitochondrial dysfunctions and sarcopenia. To test this hypothesis, we investigated the impact of Parkin overexpression in skeletal muscles of young and old mice. Parkin was overexpressed for 4 months in muscles of young (3mo) and late middle‐aged (18mo) mice using intramuscular injections of Adeno‐Associated Viruses. We show that Parkin overexpression increased muscle mass, fiber size and mitochondrial enzyme activities in both young and old muscles. In old mice, Parkin overexpression increased muscle strength, PGC‐1α content and mitochondrial density. Parkin overexpression also attenuated the aging‐related increase in 4‐hydroxynonenal content (a marker of oxidative stress), type I collagen content (a marker of fibrosis) and in the number of TUNEL‐positive myonuclei (a marker of apoptosis). Overall, our results indicate Parkin overexpression attenuates sarcopenia and unexpectedly causes hypertrophy in adult muscles. They also show that Parkin overexpression leads to increases in mitochondrial content and enzymatic activities. Finally, our results show that Parkin overexpression protects against oxidative stress, fibrosis and apoptosis. These findings highlight that Parkin may be an attractive therapeutic target to attenuate sarcopenia and improve skeletal muscle health and performance.

This article is protected by copyright. All rights reserved

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Role of the C‐terminus of SUR in the differential regulation of β‐cell and cardiac KATP channels by MgADP and metabolism

Key points

β‐Cell K_ATP channels are partially open in the absence of metabolic substrates, whereas cardiac K_ATP channels are closed. Using cloned channels heterologously expressed in Xenopus oocytes we measured the effect of MgADP on the MgATP concentration–inhibition curve immediately after patch excision. MgADP caused a far more striking reduction in ATP inhibition of Kir6.2/SUR1 channels than Kir6.2/SUR2A channels; this effect declined rapidly after patch excision. Exchanging the final 42 amino acids of SUR was sufficient to switch the Mg‐nucleotide regulation of Kir6.2/SUR1 and Kir6.2/SUR2A channels, and partially switch their sensitivity to metabolic inhibition. Deletion of the C‐terminal 42 residues of SUR abolished MgADP activation of both Kir6.2/SUR1 and Kir6.2/SUR2A channels. We conclude that the different metabolic sensitivity of Kir6.2/SUR1 and Kir6.2/SUR2A channels is at least partially due to their different regulation by Mg‐nucleotides, which is determined by the final 42 amino acids.

Abstract

ATP‐sensitive potassium (K_ATP) channels couple the metabolic state of a cell to its electrical activity and play important physiological roles in many tissues. In contrast to β‐cell (Kir6.2/SUR1) channels, which open when extracellular glucose levels fall, cardiac (Kir6.2/SUR2A) channels remain closed. This is due to differences in the SUR subunit rather than cell metabolism. As ATP inhibition and MgADP activation are similar for both types of channels, we investigated channel inhibition by MgATP in the presence of 100 μm MgADP immediately after patch excision [when the channel open probability (P _O) is near maximal]. The results were strikingly different: 100 μm MgADP substantially reduced MgATP inhibition of Kir6.2/SUR1, but had no effect on MgATP inhibition of Kir6.2/SUR2A. Exchanging the final 42 residues of SUR2A with that of SUR1 switched the channel phenotype (and vice versa), and deleting this region abolished Mg‐nucleotide activation. This suggests the C‐terminal 42 residues are important for the ability of MgADP to influence ATP inhibition at Kir6.2. This region was also necessary, but not sufficient, for activation of the K_ATP channel in intact cells by metabolic inhibition (azide). We conclude that the ability of MgADP to impair ATP inhibition at Kir6.2 accounts, in part, for the differential metabolic sensitivities of β‐cell and cardiac K_ATP channels.

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In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis

Key points

The progressive loss of motor units in amyotrophic lateral sclerosis (ALS) is initially compensated for by the reinnervation of denervated muscle fibres by surviving motor axons. A disruption in protein homeostasis is thought to play a critical role in the pathogenesis of ALS. The changes in surviving motor neurons were studied by comparing the nerve excitability properties of moderately and severely affected single motor axons from patients with ALS with those from single motor axons in control subjects. A mathematical model indicated that approximately 99% of the differences between the ALS and control units could be explained by a non‐selective reduction in the expression of all ion channels. These changes in ALS patients are best explained by a failure in the supply of ion channel and other membrane proteins from the diseased motor neuron.

Abstract

Amyotrophic lateral sclerosis (ALS) is characterised by a progressive loss of motor units and the reinnervation of denervated muscle fibres by surviving motor axons. This reinnervation preserves muscle function until symptom onset, when some 60–80% of motor units have been lost. We have studied the changes in surviving motor neurons by comparing the nerve excitability properties of 31 single motor axons from patients with ALS with those from 21 single motor axons in control subjects. ALS motor axons were classified as coming from moderately or severely affected muscles according to the compound muscle action potential amplitude of the parent muscle. Compared with control units, thresholds were increased, and there was reduced inward and outward rectification and greater superexcitability following a conditioning impulse. These abnormalities were greater in axons from severely affected muscles, and were correlated with loss of fine motor skills. A mathematical model indicated that 99.1% of the differences between the moderately affected ALS and control units could be explained by a reduction in the expression of all ion channels. For the severely affected units, modelling required, in addition, an increase in the current leak through and under the myelin sheath. This might be expected if the anchoring proteins responsible for the paranodal seal were reduced. We conclude that changes in axonal excitability identified in ALS patients are best explained by a failure in the supply of ion channel and other membrane proteins from the diseased motor neuron, a conclusion consistent with recent animal and in vitro human data.

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When muscle Ca2+ channels carry monovalent cations through gating pores: insights into the pathophysiology of type 1 hypokalaemic periodic paralysis

 Involvement of monovalent cations currents carried by muscle Ca²⁺ channels in type 1 hypokalaemic periodic paralysis (HypoPP1). A, HypoPP1 mutations in voltage‐sensing segments or in segments potentially interacting with voltage‐sensing segments generate resting inward currents through voltage‐sensing domains called gating pores carrying H⁺ or Na⁺, respectively. In normokalaemia, muscle fibres remain excitable and emit action potentials (bottom trace). B, Na⁺ or H⁺ gating pore currents when associated with hypokalaemia or with hypokalaemia plus acidosis, respectively, induced sustained depolarization and subsequent abolition of action potentials leading to muscle paralysis (bottom trace). Trains of action potentials correspond to actual recordings in an isolated mouse skeletal muscle fibre using the silicone clamp technique in the current clamp mode (C. Fuster, unpublished data).

Abstract

Patients suffering from type 1 hypokalaemic periodic paralysis (HypoPP1) experience attacks of muscle paralysis associated with hypokalaemia. The disease arises from missense mutations in the gene encoding the α1 subunit of the dihydropyridine receptor (DHPR), a protein complex anchored in the tubular membrane of skeletal muscle fibres which controls the release of Ca²⁺ from sarcoplasmic reticulum and also functions as a Ca²⁺ channel. The vast majority of mutations consist of the replacement of one of the outer arginines in S4 segments of the α1 subunit by neutral residues. Early studies have shown that muscle fibres from HypoPP1 patients are abnormally depolarized at rest in low K⁺ to the point of inducing muscle inexcitability. The relationship between HypoPP1 mutations and depolarization has long remained unknown. More recent investigations conducted in the closely structurally related voltage‐gated Na⁺ and K⁺ channels have shown that comparable S4 arginine substitutions gave rise to elevated inward currents at negative potentials called gating pore currents. Experiments performed in muscle fibres from different models revealed such an inward resting current through HypoPP1 mutated Ca²⁺ channels. In mouse fibres transfected with HypoPP1 mutated channels, the elevated resting current was found to carry H⁺ for the R1239H arginine‐to‐histidine mutation in a S4 segment and Na⁺ for the V876E HypoPP1 mutation, which has the peculiarity of not being located in S4 segments. Muscle paralysis probably results from the presence of a gating pore current associated with hypokalaemia for both mutations, possibly aggravated by external acidosis for the R1239H mutation.

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Ca2+ signalling in mouse urethral smooth muscle in situ: role of Ca2+ stores and Ca2+ influx mechanisms

Key points

Contraction of urethral smooth muscle cells (USMCs) contributes to urinary continence. Ca²⁺ signalling in USMCs was investigated in intact urethral muscles using a genetically encoded Ca²⁺ sensor, GCaMP3, expressed selectively in USMCs. USMCs were spontaneously active in situ, firing intracellular Ca²⁺ waves that were asynchronous at different sites within cells and between adjacent cells. Spontaneous Ca²⁺ waves in USMCs were myogenic but enhanced by adrenergic or purinergic agonists and decreased by nitric oxide. Ca²⁺ waves arose from inositol trisphosphate type 1 receptors and ryanodine receptors, and Ca²⁺ influx by store‐operated calcium entry was required to maintain Ca²⁺ release events. Ca²⁺ release and development of Ca²⁺ waves appear to be the primary source of Ca²⁺ for excitation–contraction coupling in the mouse urethra, and no evidence was found that voltage‐dependent Ca²⁺ entry via L‐type or T‐type channels was required for responses to α adrenergic responses.

Abstract

Urethral smooth muscle cells (USMCs) generate myogenic tone and contribute to urinary continence. Currently, little is known about Ca²⁺ signalling in USMCs in situ, and therefore little is known about the source(s) of Ca²⁺ required for excitation–contraction coupling. We characterized Ca²⁺ signalling in USMCs within intact urethral muscles using a genetically encoded Ca²⁺ sensor, GCaMP3, expressed selectively in USMCs. USMCs fired spontaneous intracellular Ca²⁺ waves that did not propagate cell‐to‐cell across muscle bundles. Ca²⁺ waves increased dramatically in response to the α1 adrenoceptor agonist phenylephrine (10 μm) and to ATP (10 μm). Ca²⁺ waves were inhibited by the nitric oxide donor DEA NONOate (10 μm). Ca²⁺ influx and release from sarcoplasmic reticulum stores contributed to Ca²⁺ waves, as Ca²⁺ free bathing solution and blocking the sarcoplasmic Ca²⁺‐ATPase abolished activity. Intracellular Ca²⁺ release involved cooperation between ryanadine receptors and inositol trisphosphate receptors, as tetracaine and ryanodine (100 μm) and xestospongin C (1 μm) reduced Ca²⁺ waves. Ca²⁺ waves were insensitive to L‐type Ca²⁺ channel modulators nifedipine (1 μm), nicardipine (1 μm), isradipine (1 μm) and FPL 64176 (1 μm), and were unaffected by the T‐type Ca²⁺ channel antagonists NNC‐550396 (1 μm) and TTA‐A2 (1 μm). Ca²⁺ waves were reduced by the store operated Ca²⁺ entry blocker SKF 96365 (10 μm) and by an Orai antagonist, GSK‐7975A (1 μm). The latter also reduced urethral contractions induced by phenylephrine, suggesting that Orai can function effectively as a receptor‐operated channel. In conclusion, Ca²⁺ waves in mouse USMCs are a source of Ca²⁺ for excitation–contraction coupling in urethral muscles.

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Challenges in unsupervised clustering of single-cell RNA-seq data

Challenges in unsupervised clustering of single-cell RNA-seq data

Challenges in unsupervised clustering of single-cell RNA-seq data, Published online: 07 January 2019; doi:10.1038/s41576-018-0088-9

Single-cell RNA sequencing (scRNA-seq) enables transcriptome-based characterization of the constituent cell types within a heterogeneous sample. However, reliable analysis and biological interpretation typically require optimal use of clustering algorithms. This Review discusses the multiple algorithmic options for clustering scRNA-seq data, including various technical, biological and computational considerations.

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Engaging Intergenerational Hispanics/Latinos to Examine Factors Influencing Childhood Obesity Using the PRECEDE–PROCEED Model

Abstract

Introduction Hispanics/Latinos are disproportionately affected by obesity in the U.S. Multiple factors place Hispanic/Latino children at risk for overweight, warranting guidance of a socio-ecologic approach to examine causes of obesity. The purpose of this study was to increase understanding of the factors that influence Hispanic/Latino childhood obesity through an intergenerational lens including children, parents/caregivers, and grandparents. Methods Eight focus groups were conducted with Hispanics/Latinos (N = 68 adults, N = 22 youth), using a semi-structured moderator's guide. Audio-recordings were transcribed, and thematically analyzed. Findings were categorized within the PRECEDE–PROCEED planning model. Results Adult participants were middle-aged (M = 37.8 ± 9.8 years) and youth were between the ages of 10–17 (M = 14.0 ± 1.8 years). Six themes emerged: eating habits, cultural perceptions of weight, acculturation, childhood obesity perceptions, economic issues, and generational differences. The major parental influence was lack of time to provide healthy meals due to socio-economic factors: long work hours and availability of nearby fast food options. Youth shared that childhood obesity is due to sedentary behaviors, permissive parenting and lack of parental modeling (the latter two factors often exacerbated by extended work schedules). Discussion Discordant perceptions about unhealthy eating habits emerged. Adults expressed a lack of nutritional knowledge and skills to prepare healthy meals; while adolescents emphasized permissive parenting styles and lack of discipline lead to unhealthy lifestyles in Hispanic families. Findings emphasize involving parents/caregivers and youth to understand discordant perceptions that can inform the development of prevention programs.

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Computational multivariate modeling of electrical activity of the porcine uterus during spontaneous and hormone‐induced estrus

New findings

What is the central question of this study?

Does estrous cycle synchronization influence myoelectrical activity of porcine myometrium?

What is the main finding and its importance?

Exogenous hormones used to synchronize estrus in pigs altered myoelectrical activity which was effectively modeled. As a result of higher order multivariate statistic modeling, we observed evidence of similar strange in both types of estrus but a larger order of EMG signals during induced estrus. The higher order statistical analysis of the probabilistic model suggests the beginning of the early‐follicular phase and the mid‐luteal phase as the most important in evaluation of the natural patterns of myoelectrical activity. We showed that the higher order multivariate cumulants are much more informative than classical statistics in the characterization of the myoelectrical activity changes in porcine myometrium.

Abstract

In pig production units, control of the estrous cycle and synchronization of ovulation have become routine herd management procedures. During the estrous cycle, under both induced and spontaneous conditions, the ovaries and the uterus undergo hormone‐dominated physiological changes, these are consistent with the hypothesis that there is a functional role of uterine contractions in promoting fertilization. We have used electromyography to determine if the use of exogenous hormones, such as eCG and hCG, that have the potential to control the time of ovulation in female pigs, changes the multivariate relations between parameters of electrical bursts and modulates the patterns of myoelectrical activity. In the study presented here, we employed the mathematical approach of higher order multivariate cumulants in complex modeling of the myometrial electrical activity. The experiment was conducted on 12 mature Polish Landrace sows and uterine activity was recorded during both spontaneous and induced estrous cycles. The burst parameters were determined using six features, in the time domain and after the Fast Fourier transformation in the frequency domain. The evaluation of myoelectrical activity patterns was conducted based on the classical univariate statistical methods and the multivariate probabilistic modelling. The classical statistical approach indicated a weaker myoelectrical activity after hormonal stimulation, whereas the higher order multivariate statistical model showed evidence of similar status of activity and larger order of signals during induced estrus. Routine estrous cycle synchronization affects the multivariate probabilistic model of myometrial electrical activity.

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