Automated exploration of DNA-based structure self-assembly networks.

Finding DNA sequences capable of folding into specific nanostructures is a hard problem, as it involves very large search spaces and complex nonlinear dynamics. Typical methods to solve it aim to reduce the search space by minimizing unwanted interactions through restrictions on the design (e.g. staples in DNA origami or voxel-based designs in DNA Bricks). Here, we present a novel methodology that aims to reduce this search space by identifying the relevant properties of a given assembly system to the emergence of various families of structures (e.g. simple structures, polymers, branched structures). For a given set of DNA strands, our approach automatically finds chemical reaction networks (CRNs) that generate sets of structures exhibiting ranges of specific user-specified properties, such as length and type of structures or their frequency of occurrence. For each set, we enumerate the possible DNA structures that can be generated through domain-level interactions, identify the most prevalent structures, find the best-performing sequence sets to the emergence of target structures, and assess CRNs' robustness to the removal of reaction pathways. Our results suggest a connection between the characteristics of DNA strands and the distribution of generated structure families.

Auditory brainstem responses in adults with autism spectrum disorder.

OBJECTIVE: To investigate possible differences in the auditory peripheral and brainstem functions between adults with autism spectrum disorder (ASD) and neurotypical (NT) adults. METHODS: Click-evoked auditory brainstem responses (ABRs) were obtained from 17 high-functioning ASD adults (aged 21-38 years) and 20 NT adults (aged 22-36 years). A relatively large number of stimulus presentations (6000) were adopted, and ABRs by horizontal and vertical electrode montages were evaluated, in order to allow precise evaluations of early ABR components. RESULTS: Waves I, II, III, and V were identified in the vertical electrode montage, and wave I and the summating potential (SP) in electrocochleograms were identified in the horizontal electrode montage. There were no significant group differences in the wave I, II, III, and V latencies or the interpeak latencies (IPLs) in the vertical electrode montage. In the horizontal montage, the ASD adults exhibited significantly shortened SP latencies compared with the NT adults, whereas there was no significant group difference in the wave I latency. CONCLUSION: The ASD adults may have the abnormalities of processing more in the peripheral auditory system than in the brainstem. SIGNIFICANCE: The current study suggests that the peripheral abnormality is associated with ASD.

Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study.

INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.

Delayed Leukoencephalopathy: A Rare Complication after Coiling of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Delayed leukoencephalopathy is a rare complication that occurs after endovascular coiling of cerebral aneurysms. We aimed to describe a clinical picture of delayed leukoencephalopathy and explore potential associations with procedural characteristics. MATERIALS AND METHODS: We considered endovascular coiling procedures for cerebral aneurysms performed between January 2006 and December 2017 in our institution with follow-up MRIs. We used logistic regression models to estimate the ORs of delayed leukoencephalopathy for each procedural characteristic. RESULTS: We reviewed 1754 endovascular coiling procedures of 1594 aneurysms. Sixteen of 1722 (0.9%) procedures demonstrated delayed leukoencephalopathy on follow-up FLAIR MR imaging examinations after a median period of 71.5 days (interquartile range, 30-101 days) in the form of high-signal changes in the white matter at locations remote from the coil mass. Seven patients had headaches or hemiparesis, and 9 patients were asymptomatic. All imaging-associated changes improved subsequently. We found indications suggesting an association between delayed leukoencephalopathy and the number of microcatheters used per procedure (P = .009), along with indications suggesting that these procedures required larger median volumes of contrast medium (225 versus 175 mL, OR = 5.5, P = .008) as well as a longer median fluoroscopy duration (123.6 versus 99.3 minutes, OR = 3.0, P = .06). Our data did not suggest that delayed leukoencephalopathy was associated with the number of coils (P = .57), microguidewires (P = .35), and guiding systems (P = .57). CONCLUSIONS: Delayed leukoencephalopathy after coiling of cerebral aneurysms may have multiple etiologies such as foreign body emboli, contrast-induced encephalopathy, or hypersensitivity reaction to foreign bodies.

Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial.

BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.

Incidence and risk factors for metabolic syndrome among urban, adult Sri Lankans: a prospective, 7-year community cohort, follow-up study.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of abdominal obesity, diabetes and prediabetes, high cholesterol and high blood pressure, that confers an increased risk of cardiovascular disease. There is limited data on incidence of MetS from South Asia. This study investigated incidence and risk factors for new onset MetS in an urban adult Sri Lankan population. METHODS: Subjects (selected by age-stratified random sampling from the Ragama Medical Officer of Health area) were screened initially in 2007 (35-64 years) and re-evaluated in 2014 (42-71 years). On both occasions they were assessed by structured interview, anthropometric measurements, liver ultrasound, and biochemical/serological tests. MetS was diagnosed on International Diabetes Federation (IDF-2006) criteria. Total body fat (TBF) and visceral fat percentage (VFP) were measured in 2014, using body impedance method. Incidence and factors at baseline, associated with new onset MetS, were investigated among those who presented for re-evaluation. RESULTS: 2985 (99.1%) [1636 (54.8%) women (54.8%); median age (IQR) 53 (47-59) years] from the initial cohort in 2007 had complete data. 2148 (71.9%) [1237 (57.6%) women; median age (IQR) 60 (54-66) years] attended follow-up. 949 of them [701 (73.9%) women; median age (IQR) 60 (54-65) years] had MetS (prevalence 47.2%, 95% CI 45.0-49.4%). Of 1246 who did not have MetS in 2007, 265 [178 (67.1%) women, median age (IQR) 57 (51-64) years] had developed MetS after 7 years (annual incidence 3.5% (95% CI 2.4-4.5%). Females (OR = 4.9, 95% CI 3.4-7.4), BMI > 23 kg/m2 in 2007 (OR = 1.6 per unit increase, 95% CI 1.5-1.7), weight gain (by 2-5% OR = 2.0, 95% CI 1.1-3.5; by > 5% OR = 2.2, 95% CI 1.4-3.4), and increase in waist circumference (by 2-5% OR = 7.0, 95% CI 4.0-12.2; by > 5% OR = 13.4, 95% CI 8.3-22.4) from baseline and presence of non-alcoholic fatty liver disease (NAFLD) in 2007 (OR = 1.70, 95% CI 1.04-2.76) were associated new onset MetS. Those with MetS had abnormal VFP and TBF in 2014 [P < 0.001]. CONCLUSION: In this study, annual incidence of MetS was 3.5%. Female gender, BMI > 23 kg/m2 and NAFLD in 2007 and increase in weight and waist circumference from baseline were significantly associated with new onset MetS. Obesity was the best predictor of future MetS.

Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka.

INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls. RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.

Earlier BMI rebound and lower pre-rebound BMI as risk of obesity among Japanese preschool children.

OBJECTIVES: Longitudinal growth data of children were analyzed to clarify the relationship between the timing of body mass index (BMI) rebound and obesity risk in later ages. SUBJECTS/METHODS: Of 54 558 children born between April 2004 and March 2005 and longitudinally measured in April and October every year in the preschool period, 15 255 children were analyzed wherein no longitudinal measurement is missing after 1 year of age. BMI rebound age was determined as the age with smallest BMI value across longitudinal individual data after 1 year of age. Rebound age was compared between overweight and non-overweight groups. The subjects were divided into groups based on the timing of rebound. The sex- and age-adjusted mean of the BMI, height and weight s.d. scores for age group, along with 6 months weight and height gain, were compared among groups using analysis of covariance. RESULTS: Among those who were overweight at 66-71 months of age, BMI rebound age obtained at approximately 3 years of age was compared with the non-overweight group, whose BMI rebound age was utmost 66 months or later (P<0.001). The comparison among BMI age group showed that earlier BMI rebound results in larger BMI (P<0.001) and larger weight and height gain after the rebound (P<0.001). Among the group with BMI rebound earlier than 30 months of age, low BMI was observed (P<0.001). Slight elevation of height and weight gain was observed before the BMI rebound among groups with rebound age earlier than 60 months of age (P<0.001). CONCLUSION: Earlier BMI rebound timing with pre-rebound low BMI leads to greater childhood obesity risk; hence, early detection and prevention is necessary for such cases.

Utility of glycosylated haemoglobin in diagnosing diabetes in an urban Sri Lankan community

Introduction: American Diabetes Association (ADA) has officially endorsed glycosylated haemoglobin (HbA1c) as a diagnostic tool. The recommended cut-off for diagnosing diabetes is  6.5%. Objectives: To compare use of HbA1c and fasting plasma glucose (FPG) to diagnose diabetes in an urban Sri Lankan community. Methods: This cross-sectional study is based on baseline data from a prospective study on non-communicable diseases in randomly selected individuals aged 35-64 years in a selected community. HbA1c was measured by National Glycohaemoglobin Standardization Program certified Bio Rad Variant HbA1c HPLC method. Diagnostic performance of HbA1c was evaluated in those without previous diabetes. Receiver Operating Characteristic Curve was used to identify optimum HbA1c threshold. Results: We studied 2516 individuals with no previous history of diabetes. Of these 53.8% were women. Mean age was 52 ± 7.9 years. FPG was 7mmol/l in 245 (9.7%). HbA1c was  6.5% in 173 (6.9%). Concordance between FPG and HbA1c was 95% (both criteria positive: 5.8%; both criteria negative: 89.2%). Compared to FPG, HbA1c cut-off of 6.5% had specificity of 98.9% (95% CI 98.3-99.3) and sensitivity of 60% (95% CI 53.6-66.2). Positive and negative predictive values were 85% (95% CI 78.8-89.9) and 95.8% (95% CI 94.9-96.6), respectively. Compared to FPG, optimum HbA1c threshold for diagnosing diabetes was 5.9% (sensitivity: 84%; specificity: 88.8%; area under the curve: 0.91). Conclusions: In the study population, detection of diabetes with ADA recommended HbA1ccriterion was 29% less than with FPG criterion. Compared to FPG, HbA1c had high specificity but sensitivity was low. Further research is needed to refine the optimum HbA1c threshold in Sri Lankans.

Longitudinal changes in body mass index of children affected by the Great East Japan Earthquake.

BACKGROUND: The evacuation and disruption in housing caused by the 2011 Great East Japan Earthquake and following nuclear radiation may have influenced child health in many respects. However, studies regarding longitudinal childhood growth are limited. Therefore, in this study we aimed to explore the influence of the earthquake on longitudinal changes in body mass index in preschool children. METHODS: Participants were children from nursery schools who cooperated with the study in the Iwate, Miyagi and Fukushima prefectures. The exposed group consisted of children who experienced the earthquake during their preschool-age period (4-5 years old). The historical control group included children who were born 2 years earlier than the exposed children in the same prefectures. Trajectories regarding body mass index and prevalence of overweight/obesity were compared between the two groups using multilevel analysis. Differences in the changes in BMI between before and after the earthquake, and proportion of overweight/obesity was compared between the two groups. We also conducted subgroup analysis by defining children with specific personal disaster experiences within the exposed group. RESULTS: A total of 9722 children were included in the study. Children in the exposed group had higher body mass indices and a higher proportion of overweight after the earthquake than the control group. These differences were more obvious when confined to exposed children with specific personal disaster experiences. CONCLUSIONS: Children's growth and development-related health issues such as increased BMI after natural disasters should evoke great attention.

Comparison of coronary heart disease risk among four diagnostic definitions of metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is now well known as one of the major risk factors for coronary heart disease (CHD). Currently, there are several methods used to define MetS. The aim of this study was to determine to what extent current MetS definition reflects CHD risk using the probability of CHD in 10 years based on Framingham risk score algorithms. METHODS: A total of 7575 adults, aged 16-93 years (2532 men and 5043 women), were recruited. We conducted a cross-sectional health survey in China using MetS criteria from four different definitions: modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), Chinese and Japanese. RESULTS: Differences in the prevalence of MetS by each definition were small in males (22.9-25.9 %), whereas in females, MetS was three times more prevalent using the IDF definition (29.1 %) versus the Japanese definition (9.7 %). Framingham risk scores in participants with MetS were significantly higher than in those without MetS by all definition criteria (p < 0.001). The CHD risk scores for participants with MetS by each definition showed similar values in males (range 11.5-12.1 %) with no significant differences among definitions. Conversely, in females with MetS the risk score for CHD was low (range 3.5-4.3 %) by each MetS definition. CONCLUSIONS: These findings suggest that further studies are required to establish appropriate criteria of MetS in females.

High-resolution mapping of bifurcations in nonlinear biochemical circuits.

Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

Risk estimates of cardiovascular diseases in a Sri Lankan community.

OBJECTIVES: Quantifying the risk of cardiovascular disease (CVD) in a community is important in planning preventive strategies, but such data are limited from developing countries, especially South Asia. We aimed to estimate the risks of coronary heart disease (CHD), total CVD, and CVD mortality in a Sri Lankan community. METHODS: A community survey was conducted in an urban health administrative area among individuals aged 35-64 years, selected by stratified random sampling. Their 10-year CHD, total CVD, and CVD mortality risks were estimated using three risk prediction tools: National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Systematic Coronary Risk Evaluation (SCORE), and World Health Organisation/ International Society of Hypertension (WHO/ISH) charts. RESULTS: Among study participants (n=2985), 54.5% were females, and mean age (SD) was 52.4 (7.8) years. According to NCEP-ATP III ('hard' CHD risk), WHO/ISH (total CVD risk), and SCORE (CVD mortality risk) criteria, 25.4% (95% CI 23.6-27.2), 8.2% (95% CI 7.3-9.2), and 11.8 (95% CI 10.5-13.1) respectively were classified as at 'high risk'. The proportion of high risk participants increased with age. 'High risk' was commoner among males (30.3% vs 20.6%, p<0.001) according to NCEPATP III criteria, but among females (9.7% vs. 6.7%, p<0.001) according to WHO/ISH criteria. No significant gender difference was noted in SCORE risk categories. CONCLUSIONS: A large proportion of individuals in this community are at risk of developing cardiovascular diseases, especially in older age groups. Risk estimates varied with the different prediction tools, and were comparatively higher with NCEP-ATP III charts.

Use of Robotic Pets in Providing Stimulation for Nursing Home Residents with Dementia.

Trial experiments utilized robotic pets to facilitate self-reliance in nursing home residents. A remote-control robot modeled clear and meaningful behaviors to elderly residents. Special attention was paid to its effects on mental and social domains. Employing the robot as a gaze target and center of attention created a cue to initiate a communication channel between residents who normally show no interest in each other. The Sony AIBO robot in this study uses commercially available wireless equipment, and all its components are easily accessible to any medical or welfare institution interested in additional practice of these activities.

Biphasic modulation by mGlu5 receptors of TRPV1-mediated intracellular calcium elevation in sensory neurons contributes to heat sensitivity.

BACKGROUND AND PURPOSE: Elevation of glutamate, an excitatory amino acid, during inflammation and injury plays a crucial role in the reception and transmission of sensory information via ionotropic and metabotropic receptors. This study aimed to investigate the mechanisms underlying the biphasic effects of metabotropic glutamate mGlu5 receptor activation on responses to noxious heat. EXPERIMENTAL APPROACH: We assessed the effects of intraplantar quisqualate, a non-selective glutamate receptor agonist, on heat and mechanical pain behaviours in mice. In addition, the effects of quisqualate on the intracellular calcium response and on membrane currents mediated by TRPV1 channels, were examined in cultured dorsal root ganglion neurons from mice. KEY RESULTS: Activation of mGlu5 receptors in hind paw transiently increased, then decreased, the response to noxious heat. In sensory neurons, activation of mGlu5 receptors potentiated TRPV1-mediated intracellular calcium elevation, while terminating activation of mGlu5 receptors depressed it. TRPV1-induced currents were potentiated by activation of mGlu5 receptors under voltage clamp conditions and these disappeared after washout. However, voltage-gated calcium currents were inhibited by the mGlu5 receptor agonist, even after washout. CONCLUSIONS AND IMPLICATIONS: These results suggest that, in sensory neurons, mGlu5 receptors biphasically modulate TRPV1-mediated intracellular calcium response via transient potentiation of TRPV1 channel-induced currents and persistent inhibition of voltage-gated calcium currents, contributing to heat hyper- and hypoalgesia.

Fear conditioning suppresses large-conductance calcium-activated potassium channels in lateral amygdala neurons.

It was previously shown that depression-like behavior is accompanied with suppression of the large-conductance calcium activated potassium (BK) channel in cingulate cortex pyramidal cells. To test whether BK channels are also involved in fear conditioning, we studied neuronal properties of amygdala principal cells in fear conditioned mice. After behavior, we made brain slices containing the amygdala, the structure critically relevant to fear memory. The resting membrane potential in lateral amygdala (LA) neurons obtained from fear conditioned mice (FC group) was more depolarized than in neurons from naïve controls. The frequencies of spikes evoked by current injections were higher in neurons from FC mice, demonstrating that excitability of LA neurons was elevated by fear conditioning. The depolarization in neurons from FC mice was shown to depend on BK channels by using the BK channel blocker charybdotoxin. Suppression of BK channels in LA neurons from the FC group was further confirmed on the basis of the spike width, since BK channels affect the descending phase of spikes. Spikes were broader in the FC group than those in the naïve control in a manner dependent on BK channels. Consistently, quantitative real-time PCR revealed a decreased expression of BK channel mRNA. The present findings suggest that emotional disorder manifested in the forms of fear conditioning is accompanied with BK channel suppression in the amygdala, the brain structure critical to this emotional disorder.

Simultaneous modified Camitz opponensplasty using a pulley at the radial side of the flexor retinaculum in severe carpal tunnel syndrome.

Camitz opponensplasty using the palmaris longus has been used in patients undergoing open carpal tunnel release. It is considered to have several advantages over other opponensplasty techniques, but it provides weak flexion and pronation, which are prerequisites for opposition. To address this shortcoming, we have used a modified Camitz procedure with a pulley at the radial side of the dissected flexor retinaculum and have assessed the results in comparison with the conventional Camitz procedure. Both procedures provided significant improvements in palmar abduction and Disabilities of the Arm, Shoulder, and Hand and Kapandji scores at 3 months post-operatively, but patients who underwent the modified Camitz procedure showed better improvement in pulp pinch, palmar abduction, and thumb pronation.

A Comparison between Revised NCEP ATP III and IDF Definitions in Diagnosing Metabolic Syndrome in an Urban Sri Lankan Population: The Ragama Health Study.

Background. The prevalence of metabolic syndrome (MetS) within individual cohorts varies with the definition used. The aim of this study was to compare the prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri Lankan population and to investigate the characteristics of discrepant cases. Methods. 2985 individuals, aged 35-65 years, were recruited to the study. Anthropometric and blood pressure measurements and laboratory investigations were carried out following standard protocols. Results. Age and sex-adjusted prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions, respectively. IDF criteria failed to identify 21% of men and 7% of women identified by the revised NCEP criteria. The discrepant group had more adverse metabolic profiles despite having a lower waist circumference than those diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan cohort regardless of the definition used. The revised NCEP definition was more appropriate in identifying the metabolically abnormal but nonobese individuals, especially among the males predisposed to type 2 diabetes or cardiovascular disease. Further research is needed to determine the suitability of the currently accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults.

The burden of diabetes mellitus and impaired fasting glucose in an urban population of Sri Lanka.

AIMS: To describe the burden of diabetes mellitus and impaired fasting glucose in middle-aged residents (35-64 years) in an urban area of Sri Lanka. METHODS: A cross-sectional survey was conducted in the Ragama Medical Officer of Health area, from which 2986 participants (1349 men and 1637 women) were randomly selected from the electoral registry between January and December 2007. The participants underwent a physical examination and had their height, weight, waist and hip circumferences and blood pressure measured by trained personnel. Fasting blood samples were taken for measurement of glucose, HbA(1c) and lipids. The prevalence of diabetes (fasting plasma glucose > 7 mmol/l) and impaired fasting glycaemia (fasting plasma glucose 5.6-6.9 mmol/l) and major predictors of diabetes in Sri Lanka were estimated from the population-based data. RESULTS: Age-adjusted prevalence of diabetes mellitus in this urban population was 20.3% in men and 19.8% in women. Through the present screening, 263 patients with diabetes and 1262 with impaired fasting glucose levels were identified. The prevalence of newly detected diabetes was 35.7% of all patients with diabetes. Among patients with diabetes, only 23.8% were optimally controlled. In the regression models, high BMI, high waist circumference, high blood pressure and hypercholesterolaemia increased the fasting plasma glucose concentration, independent of age, sex and a family history of diabetes. CONCLUSIONS: Our data demonstrate the heavy burden of diabetes in this urban population. Short- and long-term control strategies are required, not only for optimal therapy among those affected, but also for nationwide primary prevention of diabetes.

Meta-analysis of genome-wide association studies for panic disorder in the Japanese population.

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.