Dental Dynamics: A Fast New Tool for Quantifying Tooth and Jaw Biomechanics in 3D Slicer.

Teeth reveal how organisms interact with their environment. Biologists have long looked at the diverse form and function of teeth to study the evolution of feeding, fighting, and development. The exponential rise in the quantity and accessibility of computed tomography (CT) data has enabled morphologists to study teeth at finer resolutions and larger macroevolutionary scales. Measuring tooth function is no easy task, in fact, much of our mechanical understanding is derived from dental shape. Categorical descriptors of tooth shape such as morphological homodonty and heterodonty, overlook nuances in function by reducing tooth diversity for comparative analysis. The functional homodonty method quantitatively assesses the functional diversity of whole dentitions from tooth shape. This method uses tooth surface area and position to calculate the transmission of stress and estimates a threshold for functionally homodont teeth through bootstrapping and clustering techniques. However, some vertebrates have hundreds or thousands of teeth and measuring the shape and function of every individual tooth can be a painstaking task. Here, we present Dental Dynamics, a module for 3D Slicer that allows for the fast and precise quantification of dentitions and jaws. The tool automates the calculation of several tooth traits classically used to describe form and function (i.e., aspect ratio, mechanical advantage, force, etc.). To demonstrate the usefulness of our module we used Dental Dynamics to quantify 780 teeth across 20 salamanders that exhibit diverse ecologies. We coupled these data with the functional homodonty method to investigate the hypothesis that arboreal Aneides salamanders have novel tooth functions. Dental Dynamics provides a new and fast way to measure teeth and increases the accessibility of the functional homodonty method. We hope Dental Dynamics will encourage further theoretical and methodological development for quantifying and studying teeth.

Los dientes revelan cómo los organismos interactúan con su entorno. Los biólogos llevan mucho tiempo observando las diversas formas y funciones de los dientes para estudiar la evolución de la alimentación, la lucha y el desarrollo. El aumento exponencial en la cantidad y accesibilidad de los datos de la tomografía computarizada (CT) ha permitido a los morfólogos estudiar los dientes con resoluciones más finas y escalas macroevolutivas más grandes. Medir la función dental no es una tarea fácil; de hecho, gran parte de nuestro conocimiento mecánico se deriva de la forma dental. Los descriptores categóricos de la forma de los dientes, como la homodoncia y la heterodoncia morfológicas, pasan por alto los matices funcionales al reducir la diversidad de los dientes para el análisis comparativo. El método de la homodoncia funcional cuantitativamente evalúa la diversidad funcional de denticiones enteras a partir de la forma del diente. Sin embargo, algunos vertebrados tienen cientos o miles de dientes y medir la forma y función de cada uno de los dientes individuales puede ser una tarea minuciosa. Aquí te presentamos Dental Dynamics, un módulo para 3D Slicer que permite la cuantificación rápida y precisa de denticíon y mandíbulas. La herramienta automatiza el cálculo de varios rasgos dentales utilizados clásicamente para describir forma y función (es decir, relación de aspecto, ventaja mecánica, fuerza, etc.). Para demostrar la utilidad de nuestros módulos utilizamos Dental Dynamics para cuantificar 780 dientes en 20 salamandras que exhiben ecologías diversas. Combinamos estos datos con el método de homodoncia funcional para investigar la hipótesis de que las salamandras arbóreas Aneides tienen nuevas funciones dentales. Dinámica Dental proporciona una forma nueva y rápida de medir los dientes y aumenta la accesibilidad de los método funcionales de homodoncia. Esperamos que Dental Dynamics fomente más conocimientos teóricos y desarrollo metodológico para la cuantificación y estudio de los dientes.

Rugby league ball carrier injuries: The relative importance of tackle characteristics during the European Super League.

Rugby league carries a high injury incidence with 61% of injuries occurring at tackles. The ball carrier has a higher injury incidence than the defender, therefore understanding mechanisms occurring during injurious tackles are important. Given the dynamic, open nature of tackling, characteristics influencing tackle outcome likely encompass complex networks of dependencies. This study aims to identify important classifying characteristics of the tackle related to ball carrier injurious and non-injurious events in rugby league and identify the characteristics capability to correctly classify those events. Forty-one ball carrier injuries were identified and 205 matched non-injurious tackles were identified as controls. Each case and control were analysed retrospectively through video analysis. Random forest models were built to (1) filter tackle characteristics possessing relative importance for classifying tackles resulting in injurious/non-injurious outcomes and (2) determine sensitivity and specificity of tackle characteristics to classify injurious and non-injurious events. Six characteristics were identified to possess relative importance to classify injurious tackles. This included 'tackler twisted ball carrier's legs when legs were planted on ground', 'the tackler and ball carrier collide heads', 'the tackler used body weight to tackle ball carrier', 'the tackler has obvious control of the ball carrier' 'the tackler was approaching tackle sub-maximally' and 'tackler's arms were below shoulder level, elbows were flexed'. The study identified tackle characteristics that can be modified in attempt to reduce injury. Additional injury data are needed to establish relationship networks of characteristics and analyse specific injuries. Sensitivity and specificity results of the random forest were 0.995 and 0.525.

Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy.

Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan-Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89-11.08) and 10.10 months (95% CI 6.30-12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.

Prehypertension and its Risk Factors in Suburban Nepal -Findings from the Dhulikhel Heart Study.

Background Prehypertension, defined as a systolic blood pressure of 120-139 mmHg or a diastolic blood pressure of 80-89 mmHg, leads to higher rates of incident hypertension, and is associated with excess morbidity and deaths from cardiovascular diseases. Objective To estimate the prevalence of and examine the factors associated with prehypertension in Dhulikhel. Method This cross-sectional study utilized data from the 752 participants of the Dhulikhel Heart Study (DHS). The data collectors interviewed the participants at their home using a tablet based structured pre-tested questionnaire and measured blood pressure using a standard digital blood pressure machine (Microlife, Switzerland). Multivariate analysis was conducted using generalized estimating equations with multivariate logistic regression (with household as cluster) adjusting for age, sex, ethnicity, marital status, income, education, alcohol consumption, smoking, physical activity, body mass index (BMI) and food consumption. Result Males had a three-fold higher odds of prehypertension than females (OR:3.17, 95% CI:1.91-5.26). The odds of prehypertension increased with being overweight (OR:2.29, 95% CI:1.42-3.70) and with being obese (OR:5.00, 95% CI:1.81-13.79) compared to normal BMI. Education reduced the odds of developing prehypertension (OR:0.51, 95% CI:0.29-0.91). Those who met the recommended level of physical activity (OR:0.61, 95% CI:0.40-0.95) also were associated with lower prehypertension prevalence. Conclusion Obese/overweight and being male increased the odds of prehypertension whereas formal education and recommended level of physical activities were associated with lower prehypertension prevalence. Primordial prevention against cardiovascular risk factors at the community level, especially targeting the young adult male, is imperative.

Quit Intentions and Attempts among Smokers in Sub-urban Nepal: Findings from the Dhulikhel Heart Study.

Background The most effective way for smokers to avoid or minimize the harmful effects is to quit smoking. Smoking cessation has been attributed to multiple factors operating at physiological, psychological, environmental and social level. There is common consensus that smoking cessation programs should be tailored for specific populations. However, there has been lack of data regarding factors that influence smoking cessation in Nepal, which has hindered the development of effective smoking-cessation interventions. Objective To assess the prevalence of quit attempts, successful quitting and the factors associated with them in a randomly selected, population-based adult participants in sub-urban Nepal. Method This cross-sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained using the questions based on the WHO STEPS survey questionnaire and questions on past quit attempts. Result Out of 1073 participants, 248 (23.1%) were current smokers and 99 (9.2%) were former smokers. Only 58% of the current smokers mentioned that they had attempted to quit smoking. When asked if they were interested in quitting if helped, almost 90.5% mentioned they were willing. Brahmins were less likely to have quit smoking (former smoker) compared to Newars (OR: 0.41, 95% CI: 0.18-0.90). We also observed that those who had high alcohol consumption were less likely to have quit smoking (OR: 0.36, 95% CI: 0.17-0.76). We didn't find any meaningful significant association between socio-demographic factors or other CVD risk factors and the quit attempts. Conclusion As the country braces to address the burden of non-communicable diseases in Nepal, it is crucial to incorporate tobacco cessation programs in the national health system to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to get a broader understanding of quit effort and factors associated with thereby supporting the development of evidence-based strategies to address tobacco cessation.

Acute fatal sarcocystosis hepatitis in an Indo-Pacific bottlenose dolphin (Tursiops aduncus) in Hong Kong.

Unlike most species in the genus Sarcocystis, Sarcocystis canis has a broad intermediate host range. Its life cycle is incompletely known and most reports are from the USA. Here we report fatal hepatitis in a 4year old male Indo-Pacific bottlenose dolphin (Tursiops aduncus) from Hong Kong associated with a S. canis-like infection. Diagnosis was made based on clinical presentation, histopathology, transmission electron microscopy (TEM), and molecular characterization. Microscopically, S. canis-like like infection was confined to the liver. Immature and mature schizonts were found in hepatocytes and the parasite was associated with generalized hepatic necrosis. By TEM, schizonts divided by endopolygeny, and merozoites lacked rhoptries. Molecular characterization of parasites present in liver and brain tissues at the cox1 gene showed a high degree of identity (97-98%) and clustered together with Sarcocystis canis, S. lutrae, S. arctica, S. speeri, S. turdusi, and S. rileyi in a phylogenetic study. This is the first report of S. canis-like infection from Asia.

Prevalence and Correlates of Tobacco Use in a Suburban community of Nepal: Findings from the Dhulikhel Heart Study.

Background Smoking and oral tobacco use are important risk factors for cancer and other chronic diseases. The distribution of tobacco consumption in Nepal varies across the population subgroups. There is little information on the correlates of tobacco use among suburban population in Nepal. Objective To estimate the prevalence of smoking and oral tobacco use; and determine the socio-demographic and other CVD risk factors associated with them in a suburban population of Dhulikhel, Nepal. Method This cross sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained from 1073 adults age 18 years and older using the questions based on the WHO STEPS survey questionnaire. Result More than a third (36%) of the men were current smokers and 12% reported regular use of oral tobacco. About 14% of the women were current smokers and only 0.5% reported to use oral tobacco regularly.In the multivariate analysis, sex, ethnicity, education, alcohol consumption and body mass index were significantly associated with tobacco use. Males were 2.6 times as likely as females to smoke (95%: 1.53-4.59; p<0.001). Brahmin/Chhetri were 2.8 times more likely to smoke compared to Newars (95% Ci: 1.53-5.18; p=0.001). Education reduced the odds of smoking; compared to those with no formal education, those with up to high school and those with a high school degree or higher were 0.50 (95% CI: 0.27-0.92; p=0.02 ) and 0.38 (95% CI: 0.16-0.91; p=0.03) percent less likely to smoke, respectively. Moderate drinkers were 8 times more likely (95% CI: .54 - 18.40; p<0.001) and high drinkers were 13 times (95% CI: 6.63 - 24.26; p<0.001) compared to non-drinkers. Regarding oral tobacco use males were 15 times as likely as females to use oral tobacco (95% CI: 4.1-58.8; p<0.001). Compared to Newars, Brahmin/Chhetri were 2.7 times as likely to use oral tobacco (95% CI: 1.08 - 6.66; p=0.03). Conclusion Although Nepal has made some progress in passing progressive laws for tobacco control, and national surveys have shown slight reduction on tobacco use, this is far from satisfactory to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to focus on socio-cultural, gender and behavioral aspects of tobacco use in addition to the epidemiological aspects.

A Mn(iii) single ion magnet with tridentate Schiff-base ligands.

Single ion magnet behaviour is reported for a mononuclear Mn(iii) ion with tridentate Schiff-base ligands which exhibits a tetragonal Jahn-Teller elongation along the Namine-Mn-Namine axis and crystallises with two crystallographically distinct Mn(iii) cations (unit A and unit B). While magnetic measurements show a large and negative axial zero-field splitting (D = -4.73 cm(-1)), HF-EPR reveal two distinct large axial Ds (D = -4.60 cm(-1) for unit A and D = -4.18 cm(-1) for unit B), thus resulting in the largest D known to date for a Mn(iii) single ion magnet. AC magnetic measurements at 2000 Oe allowed determination of the energy barrier for spin reversal (10.19 K) and spin reversal relaxation time (1.476 × 10(-6) s) for the Mn(iii) ion. Computational studies were used to characterise the electronic structure and substantiate the zero field splitting in the Mn(iii) complex.

Challenges in assignment of orbital populations in a high spin manganese(III) complex.

Magnetic, structural and computational data of four complex salts with the same mononuclear high spin octahedral Mn(iii) complex cation are reported. The manifestation of Jahn-Teller-like distortions in the Mn(iii) cation is dependent on the nature of the charge-balancing anion, with small anions yielding a planar elongation and large anions freezing out a preferential axial elongation along one of the amine-Mn-imine directions within that same plane. Modulation of the lattice by changing the charge balancing anion results in mixing of the orbital symmetry due to vibrational perturbation.

Topographical Differences of Infant Mortality in Nepal.

Background Infant mortality is a major problem in Nepal, particularly in the mountainous region of the country. Objective To identify factors that contributes to the high rate of infant mortality in the mountain zone in Nepal. Method Data were derived from the 2011 Nepal Demographic and Health Survey (NDHS). Infant mortality was analyzed across three ecological zones in a sample of 5,306 live births in the five years preceding the survey. The contribution of risk factors to the excess infant mortality was assessed using multiple logistic regression. Result Infant mortality rate (deaths per 1000 live births) in the ecological zones were 59 (95% CI: 36, 81), 44 (35, 53), and 40 (33, 47) for the mountain, hill and terai zones, respectively. Women living in the mountain zone were more likely to report that distance to care was a "big problem" and had a greater risk of infant mortality compared to the terai zone (OR=1.42, 95% CI: 1.01, 2.02, p=0.04). This increased risk was observed only among births to mothers who perceived distance to the nearest health facility as a "big problem" (aOR=1.57, 95% CI: 1.01, 2.40, p=0.04) controlling for other risk factors. Conclusion These findings suggest that the higher Infant mortality rate (IMR) in the mountain zone was among the women who perceived distance to health facilities as a big problem. Improved accessibility to health services, particularly in this zone, is an essential strategy for reducing infant mortality in Nepal.

Estimation of Causes of Death in Suburban Nepal Using Verbal Autopsy.

Background Nepal is in the midst of a disease transition, including a rapid increase of noncommunicable diseases. In order for health policy makers and planners to make informed programmatic and funding decisions, they need up to date and accurate data regarding cause of death throughout the country. Methods of improving cause of death reporting in Nepal are urgently required. Objective We sought to validate SmartVA-Analyze, an application which computer certifies verbal autopsies, to evaluate it as a method for collecting mortality data in Nepal. Method We conducted a medical record review of mortality cases at Dhulikhel Hospital, Kathmandu University Hospital. Cases with a verifiable underlying cause of death were used as gold standard reference cases. Verbal autopsies were conducted with caregivers of 48 gold standard cases. Result Of the 66 adult gold standard mortality cases reviewed, 76% were caused by cancer, cirrhosis, cardiovascular disease, COPD or injury. When assessing concordance between cause of death from verbal autopsy vs. gold standards, we found an overall agreement (Kappa) of 0.50. Kappa based on broader ICD-10 categories was 0.69. Cause-Specific Mortality Fraction Accuracy was 0.625, and disease specific measures of concordance varied widely, with sensitivities ranging from 0-100%. Conclusion Ongoing, countrywide mortality data collection is crucial for evidence-based priority setting in Nepal. Though not valid for all causes, we found SmartVA-Analyze to provide useful general cause of death data, particularly in settings where death certification is unavailable.

A novel Alzheimer disease locus located near the gene encoding tau protein.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

Sensitive response of the Greenland Ice Sheet to surface melt drainage over a soft bed.

The dynamic response of the Greenland Ice Sheet (GrIS) depends on feedbacks between surface meltwater delivery to the subglacial environment and ice flow. Recent work has highlighted an important role of hydrological processes in regulating the ice flow, but models have so far overlooked the mechanical effect of soft basal sediment. Here we use a three-dimensional model to investigate hydrological controls on a GrIS soft-bedded region. Our results demonstrate that weakening and strengthening of subglacial sediment, associated with the seasonal delivery of surface meltwater to the bed, modulates ice flow consistent with observations. We propose that sedimentary control on ice flow is a viable alternative to existing models of evolving hydrological systems, and find a strong link between the annual flow stability, and the frequency of high meltwater discharge events. Consequently, the observed GrIS resilience to enhanced melt could be compromised if runoff variability increases further with future climate warming.

A genome-wide association meta-analysis of plasma Aß peptides concentrations in the elderly.

Amyloid beta (Aß) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aß peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aß peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aß-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aß1-40 and Aß1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aß1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aß1-42 secretion. In conclusion, our study results suggest that plasma Aß peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Risk Factors for Pneumonia in Children under 5 Years in a Teaching Hospital in Nepal.

BACKGROUND: Pneumonia is a leading cause of mortality among children under-five years of age globally. The WHO (2014) has reported that indoor air pollution caused by cooking and heating with biomass fuel, living in crowed homes and parenting smoking are risk factors of pneumonia. OBJECTIVES: The objective of the study was to identify the risk factors for pneumonia among children under-5 years of age. METHODS: A case control study was carried out among the mothers having under-5 years children who were admitted in the paediatric ward of Dhulikhel Hospital in 2012/13. A convenience sampling technique was used to select 50 children with pneumonia and 150 children with non-pneumonia diseases matched on age, sex and setting. A semi-structured interview consisting of questions related to risk factors for pneumonia was used to collect data from mothers of both cases and controls. RESULTS: Sex of the child did not differ by case/control group whereas the children with pneumonia were slightly older with 26% cases and 15% controls older than 3 years of age. Mother's education was similar in both groups as was family income. Living in a household with a chulo with smoke increased the odds of having pneumonia significantly, with the risk almost 4 times greater if the chulo was located within the same building (OR: 3.76, 95% CI: 1.20-11.82, p=0.02). Children who had diarrhea in the past 3 months were protected from pneumonia (OR: 0.38, 95% CI: 0.18- 0.82, p=0.01). An increasing trend of pneumonia was observed among children of tobacco smoking parents with greater risk if both parents smoked; it was, however, not statically significant (OR: 2.21, 95% CI: 0.56-8.82, p=0.26). CONCLUSION: The present study suggests that two factors related to smoke, presence of a smoky chulo in a household and both parents smoking, are modifiable risk factors related to pneumonia in young children. Reliable longitudinal studies, interventions, and programs to educate parents in prevention are important for reducing mortality and morbidities related to acute respiratory illnesses in Nepal.

Antibodies to heteromeric glycolipid complexes in multifocal motor neuropathy.

BACKGROUND: Measurement of anti-GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies react to heteromeric complexes of two or more glycolipids, are being increasingly applied to this area of diagnostic testing. METHODS: A newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme-linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes. RESULTS: By ELISA, 22/33 MMN cases had detectable anti-GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti-GM1 antibodies by glycoarray. Analysis of variance (anova) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycoarray. Receiver operator characteristic analysis revealed insignificantly different diagnostic performance between the two methods. However, the glycoarray appeared to offer slightly improved sensitivity by identifying antibodies in four ELISA-negative samples. CONCLUSIONS: The use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti-glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening.