Associated Impairments among Children with Cerebral Palsy in Rural Bangladesh-Findings from the Bangladesh Cerebral Palsy Register.

BACKGROUND: We aimed to describe the burden, severity, and underlying factors of associated impairments among children with cerebral palsy (CP) in rural Bangladesh. METHODS: This study reports findings from the Bangladesh Cerebral Palsy Register-the first population-based surveillance of children with CP in any LMIC, where children with confirmed CP aged < 18 years are registered by a multidisciplinary team following a standard protocol. Associated impairments were documented based on clinical assessment, available medical records, and a detailed clinical history provided by the primary caregivers. Descriptive analysis, as well as unadjusted and adjusted logistic regression, were completed using R. RESULTS: Between January 2015 and February 2022, 3820 children with CP were registered (mean (SD) age at assessment: 7.6 (5.0) y; 39% female). Overall, 81% of children had ≥1 associated impairment; hearing: 18%, speech: 74%, intellectual: 40%, visual: 14%, epilepsy: 33%. The presence of a history of CP acquired post-neonatally and having a gross motor function classification system levels III-V significantly increased the odds of different types of associated impairments in these children. Most of the children had never received any rehabilitation services and were not enrolled in any mainstream or special education system. CONCLUSIONS: The burden of associated impairments was high among children with CP, with comparatively low receipt of rehabilitation and educational services in rural Bangladesh. Comprehensive intervention could improve their functional outcome, participation, and quality of life.

Neutrophil-lymphocyte ratio in Guillain-Barré syndrome: A prognostic biomarker of severe disease and mechanical ventilation in Bangladesh.

In addition to cellular and humoral immunity, inflammatory markers play an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and are used to predict prognosis in many autoimmune diseases. The aim of this study was to identify whether the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and monocyte-lymphocyte ratio in the early stages of GBS have prognostic value for severe disease, mechanical ventilation (MV) and poor long-term outcome. A prospective cohort study of 140 adult patients with GBS and 140 healthy controls (HC) was performed in Bangladesh during 2019-2022. Clinicodemographic characteristics of the patients were recorded, and hematological parameters were measured using an automated hematology analyzer. Median patient age was 35 (44-23) years; 71% were male; 88% were severely affected (GBS Disability Score> 3); 32% required MV. Patients had higher NLR than HC (P< .0001). Among patients, elevated NLR was associated with severe GBS and MV (P= .001 and <.0001, respectively) and moderately positively correlated with poor outcomes at 4 weeks (r = 0.423). Multiple logistic regression revealed NLR was an independent risk factor for severe GBS (OR = 5.2, 95% CI = 1.6-17.4) and MV (OR = 1.5 1.1-2.1). No significant association was observed between elevated NLR and the long-term outcome of GBS. Receiver operating characteristic curves revealed NLR cut-off values of ≥ 2.432 and ≥ 4.4423 predicted severe disease (sensitivity = 71%, specificity = 75%, AUC = 0.750, 95% CI = 0.651-0.849, P = .001) and MV (sensitivity = 65.9%, specificity = 81.7%, AUC = 0.804, 95% CI=0.724-0.884; P< .001). The NLR in the early stage of GBS may represent an independent prognostic factor of severe GBS and the requirement for MV.

Antioxidant and antimicrobial potential of water lily extracts and their effects on the quality of frozen Nile tilapia (Oreochromis niloticus) fillets.

This study was investigated to evaluate the antioxidant and antimicrobial potential of water lily extracts and their effects on the quality of Nile tilapia (Oreochromis niloticus) fillets during frozen storage (-18 ± 1°C). Antioxidant and antimicrobial activities of water lily extracts, and chemical, microbiological, and sensory qualities of fish fillets were assessed. Results showed that the highest total phenolic content (34.07 mg GAE/g) and total flavonoid content (32.67 mg QE/g extract) were found in the ethanolic extract and the lowest in water extract of water lily. The ethanolic extracts of water lily also exhibited the highest antioxidant capacities and antimicrobial activities than other hydroethanolic and water extracts. The water lily extracts-treated fish fillets showed the highest potentiality in lowering the pH, total volatile basic nitrogen, and thiobarbituric acid reactive substances than the untreated fillets throughout the storage period. Moreover, ethanolic extracts of water lily exhibited comparatively higher efficacy in inhibiting bacterial growth in fish fillets than other extracts-treated fillets. The ethanolic extracts-treated fillets also showed better sensory attributes than hydroethanolic and control fillets. Therefore, ethanolic extract of water lily can be used as a natural preservative in enhancing the quality and prolonging the shelf life of Nile tilapia fillets during frozen storage.

Dietary vitamin A intake and its major food sources among rural pregnant women of South-West Bangladesh.

The study aimed to estimate the dietary intake of vitamin A and its major food sources among rural pregnant women from the southwest region of Bangladesh. A multi-stage random cluster sampling method was used to select the respondents (N = 1012). A semi-structured questionnaire was used to collect the data, and statistical analysis was conducted using IBM SPSS 20.0. The mean age of the respondents was 23.27 ± 5.23 years, and the majority were in their second (48%) and third trimester (49%). The mean dietary intake of vitamin A was 392 ± 566 µg Retinol Activity Equivalent (RAE)/day (51% of Recommended Dietary Allowance). The contribution of ß-carotene (plant source) and retinol (animal source) in vitamin A intake was about 60% and 40%, respectively. The major ß-carotene contributing food groups were vegetables (dark and light) and tubers, and food items were colocasia, potato, beans, brinjal, and ripe tomatoes. On the other hand, the major retinol-contributing food groups were fish, eggs, and milk, and food items were small fish, Rui (carp) fish, and cow's milk. It was also observed that the consumption of food items from ß-carotene and retinol-contributing food groups did not differ significantly among the three groups of respondents, but the variations in the amount of the different food items consumed were significant. Dietary vitamin A intake is low among pregnant women in the South-West region of Bangladesh. Hence, they are at a greater risk of adverse materno-fetal health outcomes associated with vitamin A deficiency.

CDK5/p35-Dependent Microtubule Reorganization Contributes to Homeostatic Shortening of the Axon Initial Segment.

The structural plasticity of the axon initial segment (AIS) contributes to the homeostatic control of activity and optimizes the function of neural circuits; however, the underlying mechanisms are not fully understood. In this study, we prepared a slice culture containing nucleus magnocellularis from chickens of both sexes that reproduces most features of AIS plasticity in vivo, regarding its effects on characteristics of AIS and cell-type specificity, and revealed that microtubule reorganization via activation of CDK5 underlies plasticity. Treating the culture with a high-K+ medium shortened the AIS and reduced sodium current and membrane excitability, specifically in neurons tuned to high-frequency sound, creating a tonotopic difference in AIS length in the nucleus. Pharmacological analyses revealed that this AIS shortening was driven by multiple Ca2+ pathways and subsequent signaling molecules that converge on CDK5 via the activation of ERK1/2. AIS shortening was suppressed by overexpression of dominant-negative CDK5, whereas it was facilitated by the overexpression of p35, an activator of CDK5. Notably, p35(T138A), a phosphorylation-inactive mutant of p35, did not shorten the AIS. Moreover, microtubule stabilizers occluded AIS shortening during the p35 overexpression, indicating that CDK5/p35 mediated AIS shortening by promoting disassembly of microtubules at distal AIS. This study highlights the importance of microtubule reorganization and regulation of CDK5 activity in structural AIS plasticity and the tuning of AIS characteristics in neurons.SIGNIFICANCE STATEMENT The structural plasticity of AIS has a strong impact on the output of neurons and plays a fundamental role in the physiology and pathology of the brain. However, the mechanisms linking neuronal activity to structural changes in AIS are not well understood. In this study, we prepared an organotypic culture of avian auditory brainstem, reproducing most AIS plasticity features in vivo, and we revealed that activity-dependent AIS shortening occurs through the disassembly of microtubules at distal AIS via activation of CDK5/p35 signals. This study emphasizes the importance of microtubule reorganization and regulation of CDK5 activity in structural AIS plasticity and tonotopic differentiation of AIS structures in the brainstem auditory circuit.

Microbial Enzymes Involved in the Biotransformation of Major Mycotoxins.

Mycotoxins, the most researched biological toxins, can contaminate food and feed, resulting in severe health implications for humans and animals. Physical, chemical, and biological techniques are used to mitigate mycotoxin contamination. The biotransformation method using whole microbial cells or isolated enzymes is the best choice to mitigate mycotoxins. Using specific enzymes may avoid the disadvantages of utilizing a full microbe, such as accidental harm to the product's organoleptic characteristics and hazardous safety features. Moreover, the degradation rates of the isolated enzymes are higher than those of the whole-cell reactions, and they are substrate-specific. Their specificity is comprehensive and is shown at the positional and/or chiral center in many circumstances. Currently, only a few enzymes of microbial origin are commercially available. Therefore, there is a need to identify more novel enzymes of microbial origin that can mitigate mycotoxins. In this review, we conducted an in-depth summary of the microbial enzymes involved in the biotransformation of mycotoxins.

Paradigm shifting of education system during COVID-19 pandemic: A qualitative study on education components.

The COVID-19 pandemic has had a far-reaching effect on the education system, leading to some changes in the conventional education system. Educational institutions are adopting alternative methods to adapt to the changed situation. The purpose of this study is to explore the changes that have taken place in the education system due to the pandemic situation. A qualitative phenomenological approach has been used to conduct the study. To get a complete picture of the shifting paradigm of the education system, two interview methods such as In-depth Interviews (IDI), Key Informant Interviews (KII) have been adopted. Interviews were taken from 15 respondents. A purposive sampling technique has been used to reach the target sample. A semi-structured questionnaire has been developed to collect necessary data. The findings of this study showed that COVID-19 pandemic has led to changes in various components of the education system. Curriculum, syllabus, assessment method, teaching method, learning method, etc., have changed in the education system. The elements of education are shifting from offline to online. The use of online-based learning materials is increasing. The curriculum has been made more flexible with a more compressed and shortened syllabus to suit the students learning under such unforeseen circumstances. Faculty should promote online study groups so that those groups can assist in providing additional support throughout specific courses. The education policy should be changed by the Bangladesh government to adapt to the changed situation.

Psychometric properties of three online-related addictive behavior instruments among Bangladeshi school-going adolescents.

BACKGROUND: Due to the ease of access to the internet in modern society users have become more prone to experiencing addictive behaviors online. The present study aimed to develop and investigate the psychometric properties of the Bangla Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), Gaming Disorder Test (GDT), and Bergen Social Media Addiction Scale (BSMAS) due to a lack of existing sound psychometric tools in Bangladesh. METHODS: A cross-sectional paper-and-pencil survey was carried out among 428 school-aged adolescents who were active gamers (90.89% males; Meanage: 16.13±1.85 years; age range: 10-19 years). Participants were recruited using convenience sampling across four selected schools in Dhaka City, Bangladesh. Data collected included sociodemographic information, frequency of internet use and gaming behaviors, psychological states (i.e., Patient Health Questionnaire [PHQ-9], Generalized Anxiety Disorder [GAD-7]), disordered gaming and social media use (i.e., IGDS9-SF, GDT, and BSMAS). Psychometric testing was conducted to examine the validity and reliability levels of the Bangla IGDS9-SF, GDT, and BSMAS. RESULTS: The newly adapted Bangla IGDS9-SF, GDT, and BSMAS exhibited adequate levels of internal consistency. All total scores were significantly correlated with depression, anxiety, frequencies of internet use/online activities and gaming, supporting criterion and convergent validity. CFA indicated excellent construct validity as all instruments had a good fit to the data. CONCLUSIONS: The findings suggest that the Bangla IGDS9-SF, GDT, and BSMAS are sound psychometric instruments due to their satisfactory psychometric properties including internal consistency, criterion validity, convergent validity, and construct validity.

SUpporting People in extreme POverty with Rehabilitation and Therapy (SUPPORT CP): a trial among families of children with cerebral palsy in Bangladesh.

AIM: To test the efficacy of an integrated microfinance/livelihood and community-based rehabilitation (IMCBR) programme in improving health-related quality of life (HRQoL) and motor function of children with cerebral palsy (CP) and gain in social capital to their ultra-poor families in rural Bangladesh. METHOD: This was an open-label cluster randomized control trial. Children with CP aged 5 years or under were randomly allocated to three arms; Arm A: IMCBR; Arm B: community-based rehabilitation (CBR); and Arm C: care-as-usual. The CBR was modified with phone follow-up followed by home-based CBR at 2.5 months post-enrolment because of the COVID-19 pandemic. Intention-to-treat analysis was performed. RESULTS: Twenty-four clusters constituting 251 children-primary caregivers' dyads were assigned to three arms (Arm A = 80; Arm B = 82; Arm C = 89). Between baseline and endline, the percentage mean change in the physical functioning domain of HRQoL was highest in Arm A (30.0%) with a significant mean difference between Arm A and Arm B (p = 0.015). Improvement in the mean social capital score was significantly higher in Arm A compared to Arm C (p < 0.001). INTERPRETATION: The findings suggest that IMCBR could improve the HRQoL of children with CP and the social capital of their ultra-poor families. Long-term follow-up of the trial participants and future exploration of such interventions are essential. The integrated livelihood and CBR programme holds potential to improve health and well-being of children with CP and their ultra-poor families.

Analysis of bioactive compounds using LC-ESI-MS/MS, cytotoxic, antimicrobial effects, and enzyme activities from Cyclotrichium origanifolium.

Cyclotrichium origanifolium is a medicinal plant belonging to the Lamiaceae family. In this study, phenolic content analysis, antimicrobial effects, and cytotoxic effects of extracts of C. origanifolium were investigated. In the extracts, phenolic compound analysis by the liquid chromatography-electrospray ionization-tandem mass spectrometry method, antimicrobial effect by the minimum inhibition concentration method, and cytotoxic effect on human dermal fibroblasts (HDF), glioblastoma cell (U87), ovarian adenocarcinoma cell (Skov-3), and human colorectal adenocarcinoma cell (CaCo-2) cancer cell lines were investigated. Cytotoxicity analyses were performed by the MTT method. In addition, the GST and AChE enzyme activities of the extracts were also measured. Around 18 compounds were detected in both the methanol and ethanol extract. It was found that the best antimicrobial effect on Gram-negative Pseudomonas aeruginosa was on methanol extract, while the ethanol extract was on Candida albicans fungus (respectively, 2.50 mg/ml, 5.0 µg/ml). A 500 µg/ml of methanol extract has been shown to have cytotoxic activity high effect on HDF cells. GST and AChE activity were found to decrease in a concentration-dependent manner.

Exogenous nitric oxide promotes salinity tolerance in plants: A meta-analysis.

Nitric oxide (NO) has received much attention since it can boost plant defense mechanisms, and plenty of studies have shown that exogenous NO improves salinity tolerance in plants. However, because of the wide range of experimental settings, it is difficult to assess the administration of optimal dosages, frequency, timing, and method of application and the overall favorable effects of NO on growth and yield improvements. Therefore, we conducted a meta-analysis to reveal the exact physiological and biochemical mechanisms and to understand the influence of plant-related or method-related factors on NO-mediated salt tolerance. Exogenous application of NO significantly influenced biomass accumulation, growth, and yield irrespective of salinity stress. According to this analysis, seed priming and foliar pre-treatment were the most effective methods of NO application to plants. Moreover, one-time and regular intervals of NO treatment were more beneficial for plant growth. The optimum concentration of NO ranges from 0.1 to 0.2 mM, and it alleviates salinity stress up to 150 mM NaCl. Furthermore, the beneficial effect of NO treatment was more pronounced as salinity stress was prolonged (>21 days). This meta-analysis showed that NO supplementation was significantly applicable at germination and seedling stages. Interestingly, exogenous NO treatment boosted plant growth most efficiently in dicots. This meta-analysis showed that exogenous NO alleviates salt-induced oxidative damage and improves plant growth and yield potential by regulating osmotic balance, mineral homeostasis, photosynthetic machinery, the metabolism of reactive oxygen species, and the antioxidant defense mechanism. Our analysis pointed out several research gaps, such as lipid metabolism regulation, reproductive stage performance, C4 plant responses, field-level yield impact, and economic profitability of farmers in response to exogenous NO, which need to be evaluated in the subsequent investigation.

Statin in Clinical and Preclinical Knee Osteoarthritis-What Evidence Exists for Future Clinical Use?-A Literature Review.

BACKGROUND: Statins are used to lower serum cholesterol. Recent preclinical and clinical research focuses on articular cartilage regeneration aspects of statin. This review summarizes the effects of statins on knee osteoarthritis (OA). METHODS: Published preclinical and clinical literature till November 2021 were searched in PubMed and PubMed Central databases. Articles not written in English, not relevant for the review, and unpublished evidence were excluded. Finally, 27 papers were reviewed and presented in the study. RESULTS: A total of 27 articles have been included-13 clinical and 14 preclinical studies. Preclinical studies showed statin-induced chondroprotective effects; these included in vitro studies on human or animal-derived degenerated articular cartilage as well as OA animal models. Chondroprotective effects of statins are thought to mediate by inhibiting the Wnt/ß-catenin signaling pathway, preventing synovial inflammation, and inhibiting catabolic-stress-induced aging of cartilage. Preclinical study outcomes were based on biochemical, macroscopic, and microscopic (histology) assessments and seemed promising in cartilage regeneration. In the 13 clinical studies, the effect of statins on human OA is inconclusive: some showing improvement of OA symptoms, and others depict signs of aggravation and radiological progression. No randomized controlled trial (RCT) has tested the efficacy of intra-articular statins in clinical knee OA, and it seems feasible to avoid oral statinassociated severe adverse effects. CONCLUSION: There are no arguments to recommend oral statins in clinical OA-knee. An RCT testing the efficacy of oral statins in patients with OA knee was never done and still seems justified, as well as a prospective phase-II clinical trial for intra-articular statins in different types of OA.

Pharmacological insights into Chukrasia velutina bark: Experimental and computer-aided approaches.

BACKGROUND: Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values. The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro, in vivo and in silico models. METHODS: The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark (MECVB) through in vitro, in vivo and in silico assays. Analgesic activity was tested using formalin-induced nociception and acetic acid-induced writhing assays while the antipyretic effect was tested using yeast-induced hyperthermia in mice model. The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay. In addition, in silico studies were conducted using computer aided methods. RESULTS: In the acetic acid-induced writhing assay, the extract showed 28.36% and 56.16% inhibition of writhing for doses of 200 and 400 mg/kg, respectively. Moreover, a dose-dependent formalin-induced licking response was observed in both early and late phase. In yeast-induced pyrexia, the MECVB exhibited (p < 0.05) antipyretic effect. The extract demonstrated an IC50 value of 78.86 µg/ml compared with ascorbic acid (IC50 23.53 µg/ml) in the DPPH scavenging assay. The compounds sitosterol, 5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I (2OYE), COX-II (6COX) and human peroxiredoxin 5 (1HD2). In ADME/T analysis, 5,7-dimethoxycoumarin and scopoletin satisfied Lipinski's rule of five and thus are potential drug candidates. CONCLUSION: The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

Epidemiology of cerebral palsy among children in the remote Gorkha district of Nepal: findings from the Nepal cerebral palsy register.

PURPOSE: To describe the epidemiology of cerebral palsy (CP) among children in Gorkha, Nepal. METHODS: We established the first population-based register of children with CP aged <18 y in Gorkha, Nepal (i.e., Nepal CP Register). Children with suspected CP underwent detailed neurodevelopmental assessment by a multidisciplinary assessment team. Socio-demographic, etiology, motor severity, rehabilitation, and educational status were documented. RESULTS: Between January and October 2018, 182 children with confirmed CP were registered (mean (standard deviation (SD)) age: 10 years 1 months (4 years 10 months), 37.4% females). The majority (88.3%) had CP acquired pre- or perinatally. Mean (SD) age of CP diagnosis was four years five months. Mothers who did not receive any formal schooling had 4.5, 3.1, and 6.3 times higher odds of having inadequate antenatal care, homebirth, and unskilled birth attendants, respectively, when adjusted for other factors. Most children had spastic CP (77.5%) and Gross Motor Function Classification System level III-V (54.9%). Overall, 45.8% had never received rehabilitation services, 58.0% of school-aged children were not attending schools. The median age of receiving rehabilitation services was three years zero months. CONCLUSIONS: The delayed diagnosis and clinical severity indicate the overall poor health status of children with CP in Nepal which could be improved by ensuring early diagnosis and intervention. Implications for rehabilitationThe first population-based cerebral palsy register in Nepal suggests diagnosis of CP is considerably delayed among children.The high burden of severe motor impairment and poor communication skill with limited access to timely rehabilitation among children with CP in Nepal is concerning.Capacity development of community-based health workers and mothers of children with CP could help implementing community-based programs for prevention and early diagnosis of CP, and to promote early intervention for children with CP in remote Gorkha, Nepal.

Novel weight estimation equation for children with cerebral palsy in low-resource settings: Validation in a population-based cohort.

AIM: To validate a novel equation to estimate weight from mid-upper arm circumference (MUAC) among children with cerebral palsy (CP) in rural Bangladesh. METHOD: Children with CP aged 2 to 18 years registered in the Bangladesh CP Register were randomly selected. Data on sociodemographics, Gross Motor Function Classification System level, and anthropometric measurements were extracted. Bland-Altman plots with a 95% agreement limit and Lin's concordance correlation coefficient with 95% confidence intervals (CI) were reported to measure agreement between observed and estimated weight. Percentage error was used to determinate the method's accuracy. RESULTS: There were 497 participants with a mean age at assessment of 9 years (SD 4 years 11 months) (47.7% female). Lin's concordance correlation coefficient between the observed and estimated weights was 0.90 (95% CI 0.89-0.92). Bland-Altman plots showed a reasonable accuracy of the equation in the study cohort. The mean percentage error of the equation was 5.04%. The average difference between observed and estimated weights was -1.02 kg (SD 5.1). The differences between observed and estimated weights were significantly greater among children with weight-for-age, height-for-age, or BMI-for-age z-scores less than or equal to -4. INTERPRETATION: It is possible to predict the weight of children with CP from MUAC with sufficient accuracy. The equation can be used for populations in low-resources and low- and middle-income countries.

An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort.

BACKGROUND AND OBJECTIVES: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. METHODS: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. RESULTS: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). DISCUSSION: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models.

Malate induces stomatal closure via a receptor-like kinase GHR1- and reactive oxygen species-dependent pathway in Arabidopsis thaliana.

A primary metabolite malate is secreted from guard cells in response to the phytohormone abscisic acid (ABA) and elevated CO2. The secreted malate subsequently facilitates stomatal closure in plants. Here, we investigated the molecular mechanism of malate-induced stomatal closure using inhibitors and ABA signaling component mutants of Arabidopsis thaliana. Malate-induced stomatal closure was impaired by a protein kinase inhibitor, K252a, and also by the disruption of a receptor-like kinase GHR1, which mediates activation of calcium ion (Ca2+) channel by reactive oxygen species (ROS) in guard cells. Malate induced ROS production in guard cells while the malate-induced stomatal closure was impaired by a peroxidase inhibitor, salicylhydroxamic acid, but not by the disruption of Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases, RBOHD and RBOHF. The malate-induced stomatal closure was impaired by Ca2+ channel blockers, verapamil, and niflumic acid. These results demonstrate that the malate signaling is mediated by GHR1 and ROS in Arabidopsis guard cells.

Arsenic, iron, and manganese in groundwater and its associated human health risk assessment in the rural area of Jashore, Bangladesh.

This study investigated groundwater pollution and potential human health risks from arsenic, iron, and manganese in the rural area of Jashore, Bangladesh. Study results show that the mean value of groundwater pH is 7.25 ± 0.31, with a mean conductivity of 633.94 ± 327.41 µs/cm, while about 73, 97, and 91% of groundwater samples exceeded the Bangladesh drinking water standard limits for As, Fe, and Mn, respectively. Groundwater pollution evaluation indices, including the heavy metal pollution index, the heavy metal evaluation index, the degree of contamination, and the Nemerow pollution index, show that approximately 97, 82, 100, and 100% of samples are in the high degree of pollution category, respectively. Spatial distribution exhibited that the study area is highly exposed to As (73%), Fe (82%), and Mn (46%). In the case of non-carcinogenic health risk via oral exposure, about 94% of samples suggest a high category of risk for infants, and 97% of samples are found to be at high risk for children and adults. The carcinogenic risk of arsenic via an oral exposure pathway suggests that approximately 97% of the samples are found to be at high risk for infants, and all of the samples are at high risk for both adults and children.

Nucleotide oligomerization domain polymorphism confers no risk to Guillain-Barré syndrome.

OBJECTIVES: Nucleotide oligomerization domain (NOD) proteins are cytoplasmic receptors that play important roles in host innate immune responses to pathogens by recognizing self or non-self-molecules and have been implicated in many autoimmune diseases including Guillain-Barré syndrome (GBS). The current study investigated whether NOD polymorphisms (NOD1-Glu266Lys, rs2075820, and NOD2- [Arg702Trp, rs2066844 and Gly908Arg, rs2066845]) contribute to ligand sensing and thus affect the susceptibility and/or severity of GBS. MATERIALS AND METHODS: We determined single nucleotide polymorphisms (SNPs) of NOD gene (NOD1-Glu266Lys and NOD2-[Arg702Trp; Gly908Ar]) in 303 patients with GBS and 303 healthy controls from Bangladesh by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. Genotypes and allele frequencies were compared by performing chi-squared or Fisher's exact test with Yates' continuity correction. Serology for Campylobacter jejuni and anti-GM1 antibodies were determined by enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: NOD variants (NOD1-Glu266Lys and NOD2- [Arg702Trp; Gly908Arg]) were not associated with susceptibility and severity of GBS when compared with healthy controls and mild or severe form of disease. Moreover, NOD2 polymorphisms showed wild-type NOD2 C2104 and NOD2 G2722, respectively, with homozygous Arg/Arg genotype of NOD2 (Arg702Trp) polymorphism and homozygous Gly/Gly genotype of NOD2 (Gly908Arg) for all study subjects in Bangladesh. Homogenous distribution of NOD1 genotypes was observed in patients with axonal and demyelinating form of GBS. CONCLUSIONS: NOD variants confer no risk to the susceptibility and severity of GBS. Moreover, NOD2 polymorphism is rare or absent in patients with GBS as well as in the healthy individuals of Bangladesh.

Neuropharmacological and Antidiarrheal Potentials of Duabanga grandiflora (DC.) Walp. Stem Bark and Prospective Ligand-Receptor Interactions of Its Bioactive Lead Molecules.

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches in Swiss albino mice and a computer-aided molecular approach. The forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), and hole board test (HBT) were used to determine anti-depressant and anxiolytic activity in experimental mice. In addition, anti-diarrheal studies were performed using castor oil-induced diarrhea, castor oil-induced enter pooling, and the charcoal-induced gastrointestinal motility test. MEDG showed substantial depletions in the immobility times in both FST and TST after treatment with the MEDG extract, whereas moderate anxiolytic activity was manifested at a higher dose (400 mg/kg) compared with the control. Correspondingly, MEDG extract revealed a significant reduction in wet feces and decreased the small intestinal transit of charcoal meal in castor oil-induced diarrhea and charcoal-induced gastrointestinal motility test. In the computer-aided molecular approaches, vanillin displayed a promising binding score for both anxiolytic and anti-diarrheal activities, while duabanganal C showed a promising score for the anti-depressant activity. The present experimental findings along with a computer-aided model conclude that MEDG could be a possible Phyto therapeutic agent with potential anti-depressant, anxiolytic and anti-diarrheal activity.