Quantitative and qualitative analysis of stability for 16 serum immunoregulators over 50 freeze-thaw cycles.

OBJECTIVES: To evaluate the reliability of data from the assay of bio-archived specimens, a 50-freeze-thaw-cycle (FTC) degradation study of fresh sera was conducted to test the stability of 16 immunoregulators. METHODS: Twenty de-identified serum specimens were obtained from volunteers at United Health Services-Wilson Memorial Hospital. Specimens were stored at -20°C and underwent daily 1 h thawing and subsequent freezing for each FTC over 50 consecutive days. Immunoregulator concentrations were assessed via enzyme-linked immunosorbent assay (ELISA) in participant samples at 2 FTC (baseline), 25 FTC, and 50 FTC. Specific immunoregulators observed in the study were C-reactive protein (CRP), interleukin (IL)-1α, 4, 6, 8, 10, monocyte chemoattractant protein-1 (MCP-1, CCL2), monocyte chemoattractant protein-2 (MCP-2, CCL8), eotaxin-1, thymus-and-activation-regulated chemokine (TARC, CCL17), regulated on activation normal T-cell expressed and secreted (RANTES, CCL5), growth-regulated oncogene-alpha (GRO-α, CXCL1), small inducible cytokine A1 (I-309, CCL1), interferon-gamma (IFN-γ), interferon-gamma inducible protein-10 (IP-10, CXCL10), and tumor necrosis factor-alpha (TNF-α). RESULTS: Quantitative stability of serum immunoregulators: Serum CRP, IL-8, IL-10, IFN-γ, IP-10, and eotaxin-1 levels appear to be statistically equivalent from baseline to 50 FTC (p ≤ .05). Retention of patterns in serum immunoregulators: patterns across FTC were retained for TARC (age) and CRP, IFN-γ, and MCP-2 (sex). CONCLUSIONS: While the effect of multiple FTC on serum immunoregulator levels may not replicate prolonged freezer storage, the results of this study provide valuable information on the robustness of immunoregulators for research using bio-archived sera.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Fetal cardiac and neonatal cerebral hemodynamics and oxygen metabolism in transposition of the great arteries.

OBJECTIVES: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls. METHODS: Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2 ) and an index of microvascular cerebral blood flow (CBFi ), along with peripheral arterial oxygen saturation (SpO2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. RESULTS: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA-VSD group. During the predischarge period, SO2 was higher in TGA-IVS than in TGA-VSD neonates, while CBFi was lower. CONCLUSIONS: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The origin and impact of bound water around intrinsically disordered proteins.

Proteins and water couple dynamically over a wide range of time scales. Motivated by their central role in protein function, protein-water dynamics and thermodynamics have been extensively studied for structured proteins, where correspondence to structural features has been made. However, properties controlling intrinsically disordered protein (IDP)-water dynamics are not yet known. We report results of megahertz-to-terahertz dielectric spectroscopy and molecular dynamics simulations of a group of IDPs with varying charge content along with structured proteins of similar size. Hydration water around IDPs is found to exhibit more heterogeneous rotational and translational dynamics compared with water around structured proteins of similar size, yielding on average more restricted dynamics around individual residues of IDPs, charged or neutral, compared with structured proteins. The on-average slower water dynamics is found to arise from excess tightly bound water in the first hydration layer, which is related to greater exposure to charged groups. The more tightly bound water to IDPs correlates with the smaller hydration shell found experimentally, and affects entropy associated with protein-water interactions, the contribution of which we estimate based on the dielectric measurements and simulations. Water-IDP dynamic coupling at terahertz frequencies is characterized by the dielectric measurements and simulations.

Morton's neuroma: review of anatomy, pathomechanism, and imaging.

Morton's neuroma is a commonly encountered cause of forefoot pain, which may limit weight-bearing activities and footwear choices. Although the aetiology and pathomechanism of this condition is controversial, the histological endpoint is well established as benign perineural fibrosis of a common plantar digital nerve, typically within the third intermetatarsal space. The diagnosis of Morton's neuroma is mainly based on characteristic symptoms and clinical findings, but may be confirmed by ultrasonography. Although ultrasound is a highly accurate diagnostic tool for Morton's neuroma, it is subject to interoperator variability due to differences in technique and level of experience. In this paper, the authors review the anatomy of the common plantar digital nerves and surrounding structures in the forefoot, which are deemed relevant to the understanding of Morton's neuroma, especially from a sonographic point of view. Several theories of the pathomechanism of Morton's neuroma are briefly discussed. The main purpose of this article is to illustrate the ultrasound techniques for evaluating Morton's neuroma and performing ultrasound-guided corticosteroid injections.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

An epidemiological profile of chronic obstructive pulmonary disease: A community-based study in Delhi.

BACKGROUND: Different definitions used for chronic obstructive pulmonary disease (COPD) preclude getting reliable prevalence estimates. Study objective was to find the prevalence of COPD as per standard Global Initiative for Chronic Obstructive Lung Disease definition, risk factors associated, and treatment seeking in adults >30 years. METHODOLOGY: Community-based cross-sectional study was conducted in Delhi, among 1200 adults, selected by systematic random sampling. Pretested questionnaire was used to interview all subjects and screen for symptoms of COPD. Postbronchodilator spirometry was done to confirm COPD. STATISTICAL ANALYSIS: Adjusted odds ratio (aOR) was calculated by multivariable analysis to examine the association of risk factors with COPD. Receiver operating characteristic (ROC) curve was developed to assess predictability. RESULTS: The prevalence of COPD was 10.1% (95% confidence interval [CI] 8.5, 11.9%). Tobacco smoking was the strongest risk factor associated (aOR 9.48; 95% CI 4.22, 14.13) followed by environmental tobacco smoke (ETS), occupational exposure, age, and biomass fuel. Each pack-year of smoking increased 15% risk of COPD. Ex-smokers had 63% lesser risk compared to current smokers. Clinical allergy seems to preclude COPD (aOR 0.06; 95% CI 0.02, 0.37). ROC analysis showed 94.38% of the COPD variability can be assessed by this model (sensitivity 57.4%; positive predictive value 93.3%). Only 48% patients were on treatment. Treatment continuation was impeded by its cost. CONCLUSION: COPD prevalence in the region of Delhi, India, is high, and our case-finding population study identified a high rate of patients who were not on any treatment. Our study adds to creating awareness on the importance of smoking cessation, early diagnosis of COPD, and the need for regular treatment.

New tissue priors for improved automated classification of subcortical brain structures on MRI.

Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains.

Complex patterns of spatially extended generators of epileptic activity: Comparison of source localization methods cMEM and 4-ExSo-MUSIC on high resolution EEG and MEG data.

Electric Source Imaging (ESI) and Magnetic Source Imaging (MSI) of EEG and MEG signals are widely used to determine the origin of interictal epileptic discharges during the pre-surgical evaluation of patients with epilepsy. Epileptic discharges are detectable on EEG/MEG scalp recordings only when associated with a spatially extended cortical generator of several square centimeters, therefore it is essential to assess the ability of source localization methods to recover such spatial extent. In this study we evaluated two source localization methods that have been developed for localizing spatially extended sources using EEG/MEG data: coherent Maximum Entropy on the Mean (cMEM) and 4th order Extended Source Multiple Signal Classification (4-ExSo-MUSIC). In order to propose a fair comparison of the performances of the two methods in MEG versus EEG, this study considered realistic simulations of simultaneous EEG/MEG acquisitions taking into account an equivalent number of channels in EEG (257 electrodes) and MEG (275 sensors), involving a biophysical computational neural mass model of neuronal discharges and realistically shaped head models. cMEM and 4-ExSo-MUSIC were evaluated for their sensitivity to localize complex patterns of epileptic discharges which includes (a) different locations and spatial extents of multiple synchronous sources, and (b) propagation patterns exhibited by epileptic discharges. Performance of the source localization methods was assessed using a detection accuracy index (Area Under receiver operating characteristic Curve, AUC) and a Spatial Dispersion (SD) metric. Finally, we also presented two examples illustrating the performance of cMEM and 4-ExSo-MUSIC on clinical data recorded using high resolution EEG and MEG. When simulating single sources at different locations, both 4-ExSo-MUSIC and cMEM exhibited excellent performance (median AUC significantly larger than 0.8 for EEG and MEG), whereas, only for EEG, 4-ExSo-MUSIC showed significantly larger AUC values than cMEM. On the other hand, cMEM showed significantly lower SD values than 4-ExSo-MUSIC for both EEG and MEG. When assessing the impact of the source spatial extent, both methods provided consistent and reliable detection accuracy for a wide range of source spatial extents (source sizes ranging from 3 to 20cm2 for MEG and 3 to 30cm2 for EEG). For both EEG and MEG, 4-ExSo-MUSIC localized single source of large signal-to-noise ratio better than cMEM. In the presence of two synchronous sources, cMEM was able to distinguish well the two sources (their location and spatial extent), while 4-ExSo-MUSIC only retrieved one of them. cMEM was able to detect the spatio-temporal propagation patterns of two synchronous activities while 4-ExSo-MUSIC favored the strongest source activity. Overall, in the context of localizing sources of epileptic discharges from EEG and MEG data, 4-ExSo-MUSIC and cMEM were found accurately sensitive to the location and spatial extent of the sources, with some complementarities. Therefore, they are both eligible for application on clinical data.

The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.

BACKGROUND: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences. AIM: To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR). METHOD AND RESULTS: Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies. CONCLUSIONS AND RELEVANCE: Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.

Pattern of Pulmonary Involvement and Outcome of Aspiration Pneumonia in Patients with Altered Consciousness Admitted in Dhaka Medical College Hospital.

Aspiration is well recognized as a cause of pulmonary disease and is not uncommon in patients with altered consciousness.The mortality rate of aspiration pneumonia is approximately 1% in outpatient setting and upto 25% in those requiring hospitalization. This study was done to see the pattern of pulmonary involvement and outcome of aspiration pneumonia in patients with altered consciousness admitted in medicine department of a tertiary care hospital in our country. This was a prospective observational study conducted among the 52 adult patients of aspiration pneumonia with altered consciousness admitted in the medicine department of Dhaka Medical College Hospital (DMCH), during June 2010 to December 2010. Aspiration pneumonia was confirmed by clinical examination and laboratory investigations. Hematologic measurements (TC of WBC, Hb%, ESR, platelet count), chest X-ray, blood gas analysis, blood urea, creatinine and random blood sugar, sputum for Gram staining, sputum for culture sensitivity and blood culture were done in all patients.Assessment of altered conscious patient was done by application of the Glasgow Coma Scale. Case record forms with appropriate questionnaire were filled for all patients. The mean±SD age was 57.42±13.63 years with ranged from 25 to 90 years. Out of 52 patients, 37(71.15%) patients were male and 15(28.85%) patients were female. Following aspiration 76.92% patients developed pneumonitis, 13.46% patients developed lung abscess and only 9.62% patients developed ARDS. Most (33) of the patients had opacity in right lower zone and 13 patients had opacity in the left lower zone, 6 patients had opacity in right mid zone. Only 10 patients had opacity in both lower zones. In this study overall mortality rate was 23%. If only one lobe was involved radiologically, mortality was 8.33%. If two or more lobes on one or both sides were involved, mortality was in the range of 25-91%.

Allergic Rhinitis: A neglected disease - A community based assessment among adults in Delhi.

BACKGROUND AND OBJECTIVES: Allergic Rhinitis is rather erroneously viewed as a trivial disease. It is important in that it can significantly affect quality of life. There is paucity of community based prevalence studies on the disease in India. This study was planned to assess the prevalence of allergic rhinitis in adults, the proportion of asthmatics among them, risk factors associated and treatment seeking behaviour among the patients. MATERIALS AND METHODS: A community based cross sectional study was conducted in Mehrauli, South Delhi among 1200 adults, aged 30 years and over selected by systematic random sampling from two randomly selected wards. A pre-tested questionnaire was used to collect information regarding symptoms, risk factors and treatment seeking behaviour. Allergic Rhinitis was diagnosed as per ARIA guidelines. Spirometry was done to diagnose asthma among them. Multivariate logistic regression analysis was done to find the association of risk factors with disease. RESULTS: The prevalence of Allergic Rhinitis was found to be 11% (132 subjects) and 33.3% (44 patients) among them also had asthma. Overcrowding (aOR = 6.4), absence of cross-ventilation (aOR = 2.5), occupational exposure to dust/ smoke (aOR = 2.1), tobacco smoking (aOR = 2.1), family history of allergic diseases (aOR = 2.7) and clinical allergy (aOR = 10.2) were found to be independent risk factors associated with Rhinitis. More patients of Rhinitis with asthma (75%) took treatment, relative to those without asthma (40%) who, mostly relied on home remedies (42%) or, did not seek any treatment (18%) (P = 0.031). Interpretations and Conclusion: The burden of Allergic Rhinitis is high with a considerable overlap with asthma. These allergic diseases and emphasize the importance of early and regular treatment.

Postnatal Support Strategies for Improving Rates of Exclusive Breastfeeding in Case of Caesarean Baby.

Despite awarness of the many advantages of breast feeding exclusive breastfeeding (EBF) rate is still lower than recommended practice and the rate is less in case of caesarean baby. In an effort towards achieving better breast feeding practices, UNICEF and WHO launched the baby friendly hospital initiative in 1991 to ensure that all maternity facilities support mothers in making the best choice about feeding. The implementation of effective programs improves rates of short and long term exclusive breast feeding even in case of caesarean baby. The objective of present study was to investigate whether postnatal support improves the rate of exclusive breast feeding in case of caesarean baby compared with usual hospital care. This was a longitudinal study over one and half year period, from April 2009 to October 2011 done in Combined Military Hospital in Mymensingh. A total of 565 pregnant women were included this study. Primary outcome was early establishment of breast feeding after caesarean section. Secondary outcome was exclusive breast feeding at discharge from hospital, two weeks and six weeks after caesarean section delivery. Early establishment of breast feeding within one hour after caesarean section was higher in postnatal support group than usual care group (70.29% vs. 57.14%). Rates of exclusive breastfeeding in the postnatal support strategies group were significantly higher when compared with those who received usual hospital care at discharge (89.13% vs. 75.94%, p=0.004), at 2 weeks (85.51% vs. 53.38%, p<0.001) and at 6 weeks (74.64% vs. 38.35%, p<0.001). Postnatal lactation support, as single intervention based in hospital significantly improves rates of exclusive breast feeding.

Clinical Profile of Peripheral Neuropathy in Leprosy.

The objectives of the study were to see the association of peripheral neuropathy in leprosy and to find out the clinical profile of peripheral neuropathy and disability status in leprosy. It was descriptive type of cross sectional study was conducted among the cases of leprosy attended in the out-patient departments of neurology, Mymensingh Medical College Hospital (MMCH) and Mymensingh tuberculosis and leprosy hospital that fulfilled the inclusion criteria were included in this study, during the study period of January 2010 to December 2011.In this study of 62 cases revealed that leprosy is more common in male (71%) people and 21% leprosy patient had contact with known case of leprosy. Leprosy causes peripheral neuropathy (61.3%). Duration of occurrence of peripheral neuropathy was prolonged (>6 month) in most of the patients (47.4%) and the disease progression was also slow (63.2%). Numbness was complained by 89.4% patients and 65.8% subjects complained of weakness of limbs. Deformities and ulcers were present in 26.3% and 50% of patients respectively. Ulnar nerve (43.6%), Lateral popliteal nerve (41.9%), Posterior tibial nerve (41.9%) and Great auricular nerve (17.7%) were the most commonly involved thickened peripheral nerves. The rate of visible physical impairment (WHO Grade 2 disability) among people affected by leprosy in feet was 27.4% and in hands was 16.1%. The position and vibration sense was found to normal all patients of peripheral neuropathy.

Circadian rhythm of onset of stroke - in 50 cases of ischemic stroke.

Stroke is a leading cause of death and disability worldwide. While the immediate consequence of stroke include permanent cognitive deficits, paralysis, visual impairment and sensory disturbances; stroke also results in long term dysregulation of sleep and mood, which may be equally disabling. The influence of ischemic stroke on circadian rhythm regulation, which is strongly linked to sleep and mood, may thus potentially influence long term recovery in stroke patients. Stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. This study was done to find out the time of onset of most of the ischemic stroke attack and to determine the outcome of ischemic stroke during hospital stay. All ischemic stroke patients admitted in Medicine wards in Comilla Medical College Hospital during the period of 1st November 2010 to 30th April 2011 included in this study. After admission, a careful history and a thorough clinical examination was carried out. Data collection was done on a preset questionnaire which involved to identify the risk factors, the time of onset of ischemic stroke, and outcome during hospital stay. All the cases were investigated. Among the 50 ischemic stroke patients, 68% were male and 32% female. Maximum age groups were 61-70 years (50%). By occupational category, maximum were retired persons (46%); 68% were hypertensive, 38% smoker and 16% had diabetes. Dyslipidemia was present in 44% patients. Most of the ischemic stroke (44%) occurred in the morning to late morning (6:01AM-12:00PM) and majority (80%) of the patients was discharged with residual neurological dysfunction. This study supports the presence of a circadian pattern in the onset of ischemic stroke, with higher risk in the morning to late morning. Most of the patients were discharged with residual neurological dysfunction.

Disentangling in vivo the effects of iron content and atrophy on the ageing human brain.

Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer - MT, from healthy subjects (n=96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.

Optimistic update bias increases in older age.

BACKGROUND: Healthy older adults report greater well-being and life satisfaction than their younger counterparts. One potential explanation for this is enhanced optimism. We tested the influence of age on optimistic and pessimistic beliefs about the future and the associated structural neural correlates. METHOD: Eighteen young and 18 healthy older adults performed a belief updating paradigm, measuring differences in updating beliefs for desirable and undesirable information about future negative events. These measures were related to regional brain volume, focusing on the anterior cingulate cortex (ACC) because this region is strongly linked to a positivity bias in older age. RESULTS: We demonstrate an age-related reduction in updating beliefs when older adults are faced with undesirable, but not desirable, information about negative events. This greater 'update bias' in older age persisted even after controlling for a variety of variables including subjective rating scales and poorer overall memory. A structural brain correlate of this greater 'update bias' was evident in greater grey matter volume in the dorsal ACC in older but not in young adults. CONCLUSIONS: We show a greater update bias in healthy older age. The link between this bias and relative volume of the ACC suggests a shared mechanism with an age-related positivity bias. Older adults frequently have to make important decisions relating to personal, health and financial issues. Our findings have wider behavioural implications in these contexts because an enhanced optimistic update bias may skew such real-world decision making.

First Report of Sudden Death Syndrome of Soybean Caused by Fusarium virguliforme in South Dakota.

During the 2012 soybean growing season, soybean (Glycine max (L.) Merr.) plants submitted to South Dakota State University Plant Diagnostic Clinic exhibited symptoms typical of sudden death syndrome (SDS) caused by Fusarium virguliforme (Aoki, O'Donnell, Homma, & Lattanzi). In the 2013 soybean growing season, a soybean survey targeting SDS-symptomatic plants was carried out in 20 eastern South Dakota counties between July and August when plants were at the beginning seed and beginning seed maturity growth stages. Soybean plants with SDS-like symptoms were found in eight counties at very low incidence (<3%). Approximately 15 plants per field that had symptoms resembling those of SDS were collected and fungal isolations were made. Leaf symptoms included some necrosis and slight interveinal chlorosis. The tap roots also had areas of necrosis and the vascular system was brown. Isolations were made from the symptomatic tap root sections. The tap root sections were surface sterilized using a 10% NaOCl for 1 min and then rinsed once for 1 min with sterile water before being placed on an acidified potato dextrose agar. Slow growing isolates of F. virguliforme with characteristic blue sporodochia were isolated from these symptomatic plant roots. The conidia were banana-shaped with 4 to 5 septae, a typical characteristic for F. virguliforme. Koch's postulates were performed using a modified layer test method (2). Briefly, the conidia from the isolate (PL1200158 from Yankton county, SD) was used to infest sterile sorghum seed. In the greenhouse, three holes were punched in the bottom of 32 oz. Styrofoam cups. The bottom 11 cm of the cup was then filled with vermiculite. A 2-cm layer of fully colonized sorghum seed was placed on top of the vermiculite. This was covered with a 2- to 5-cm layer of vermiculite. Fifteen soybean cv. Sloan seeds were placed on top of this vermiculite layer and covered with approximately 2 cm more vermiculite for each cup for a total of 12 cups. The temperature in the greenhouse was approximately 23°C with 14 h of light and 10 h of darkness for 21 days. Leaves began to show necrosis and the roots had brown, rotted lesions. Symptoms did not develop on non-inoculated controls. After 5 weeks under greenhouse conditions, the roots of infected plants were removed, surface sterilized, and F. virguliforme was re-isolated. SDS was further confirmed by PCR using primers designed from FvTox1 gene. FvTox1, a single-copy gene, has been found to be highly species specific and primers from this region delineate F. virguliforme from other Fusarium species (1). The PCR product size matched that of expected size. The PCR product was sequenced and a BLAST search matched (100%) only the sequences of F. virguliforme FvTox1 gene (GenBank Accession No. JF440964). The confirmation of SDS in eight counties in South Dakota indicates that SDS may be widespread and a concern for soybean production when conditions are conducive for SDS to develop. References: (1) G. C. Y. Mbofung, et al. Plant Dis. 95:1420, 2011. (2) A. F. Schmitthenner and R. G. Bhatt. Useful Methods for Studying Phytophthora in the Laboratory. Special Circular, Ohio Agricultural Research and Development Center, Wooster, OH, 1994.

Precipitating factor of seizure in epilepsy: experience in a tertiary care hospital.

Patients with epilepsy experience recurrent, unprovoked seizures. In most of the cases seizure occurs spontaneously, but there may be association with various triggers. These triggers may act as seizure precipitating factors (SPFs). This study was done to find out the most common SPFs and their relationship to different types epileptic patients attending a tertiary care hospital in Bangladesh. This cross sectional study was carried out in specialized epilepsy weekly outdoor clinic and Medicine outpatient department (OPD) of Dhaka Medical College Hospital from January 2008 to July 2011, which included 1168 epilepsy patients. All patients attending the clinic were included in the study. Epilepsy syndromes were broadly classified into four categories using the classification system of international league against epilepsy (ILAE) namely, generalized epilepsy (GE), localization related epilepsy (LRE), symptomatic and unclassified. Each patient was evaluated and classified by consultant neurologist. All participants were interviewed through a predesigned close ended questionnaire that included a long list of 30 precipitating factors. Among all the patients 71.5% were male, with most common age group 11-20 years (36.8%). About 62% could indentify at least one precipitator. Excitation (25.2%) was the most common SPF reported by patients followed by emotional stress in 17.7%. Fever precipitated seizure in 16.4% of the subjects. A good number of them (15.5%) noticed that whenever there was sleep deprivation, they had an attack of epilepsy. However, drug withdrawal, playing outside and head trauma were also common among the patients, about 11.7%, 11.3% and 8.4% respectively. Most of the patients can identify their seizure precipitant and clustering of many SPFs suggests a common patho-physiologic mechanism for these triggers. Excitation, sleep deprivation, fever, watching television and head trauma showed a strong association with generalized epilepsy. Patients with seizure disorder should be evaluated for presence of SPFs, because identification of these might help in proper management of epilepsy.

Outcome of early active mobilization in flexor tendon repair in zone II in hand.

Early controlled motion programs after flexor tendon repair in zone II of hand are designed to minimize adhesion formation by promoting the excursion of repaired tendons. The flexor tendon surgery especially in zone II is complicated. It is simplest in the newly injured and unscarred digit and the results of correctly rehabilitated primary repair are likely to be the best attainable. We conducted a study including 18 patients with 52 digits involving 80 flexor tendons in zone II to observe and record the result of the primary or delayed primary repair with early active mobilization protocol. Thirteen (72.22%) patients were below 30 years of age. Sixteen cases (88.89%) were sustained injury by sharp instrument either accidentally or by assault. Ring and little finger were involved in 50% instances. The repair was done with the modified Kessler core suture technique with locking epitendinous sutures with a knot inside the repair site, using polypropylene 4-0 and 6-0 sutures. The final assessment was done at 6 months post repair using the Louisville system of Lister et al. 61.54% (n=32) digits were shown excellent result whereas good results were seen in 23% (n=12) digits. Fair was shown 7.69% (n=4) digits and 7.69% (n=4) digits were shown poor results. P value was <0.001 by Z test which is significant. Complications included tendon rupture in 3(5.77%) cases (one thumb, one ring and one little finger) and contracture in 4(7.69%) cases whereas superficial infection and flap necrosis was seen in one (1.92%) case each. The primary or delayed primary repair of cut flexor tendons in zone II using the modified Kessler core suture and epitendinous suture with early active mobilization protocol has been given good result, with minimal complications.