Saccharomyces cerevisiae survival against heat stress entails a communication between CCT and cell wall integrity pathway.

The chaperonin TRiC/CCT is cytosolic cylindrical complex of 16 subunits encoded by eight essential genes CCT1-8. It contributes to folding 10% of cellular polypeptides in yeast. The strain carrying substitution point mutation G412E in the equatorial domain of Cct7p resulted in the improper folding of substrates. In this study, the Cct7p mutant exhibited sensitivity to non-optimal growth temperatures and cell wall stressors. Heat shock is known to disrupt cell wall and protein stability in budding yeast. Mitogen-activated protein kinase-mediated cell wall integrity pathway gets activated to compensate the perturbed cell wall. Overexpression of the PKC1 and SLT2 genes of MAPK signaling pathway in mutant rescued the growth and cell division defects. Additionally, the genes of the CWI pathway such as SED1, GFA1, PIR1, and RIM21 are down-regulated. The Cct7p mutant strain (G412E) is unable to withstand the heat stress due to the underlying defects in protein folding and cell wall maintenance. Taken together, our results strongly indicate the interaction between CCT and cell wall integrity pathway.

Early Inflammatory Response of Dental Pulp in Response to Biodentin and Mineral Trioxide Aggregate as Pulp-capping Agents.

This study was carried out to observe immediate inflammatory response of Human Dental Pulp capped with Biodentin and Mineral Trioxide Aggregate (MTA). This prospective clinical study was carried out in the Department of Conservative Dentistry and Endodontics together with the Department of Orthodontia, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from 2016 to 2018. A total number of eighty (80) permanent premolars teeth planned to be extracted for orthodontic alignment of occlusion were used as study sample. Those teeth were divided into two groups; Group A and Group B, having 40 teeth in each (n=40). An occlusal exposure of approximately 1.5mm in diameter was made. Then in -group A, exposed pulp were capped with 2-mm-thick layer of sterile Biodentin (Septodont) and in-group B with ProRoot White MTA (Dentsply). After pulp capping with the experimental material in respective group, cavities in all teeth were restored with glass ionomer cement. After 24 hours the teeth were extracted, fixed in 10% buffered formalin solution, then decalcified by 10.0% nitric acid and embedded in paraffin. Now 2 to 3-micron-thick serial sections were made in the linguo-buccal plane and finally stained with hematoxylin-eosin. Now pulpal inflammation in respect of type, intensity and extension, were determined by using a predetermined evaluation criterion under an optical microscope at 40× magnifications. Statistical differences among the experimental groups were analyzed by Descriptive analysis (Cross Tabulation) (p<0.05). Histologically both the tested materials produced immediate pulpal tissue reaction. 'Biodentin' found to be most immediate pulpal tissue reactive (reactive in 100% cases), Whereas, MTA produced immediate tissue reaction only in 50.0% cases. Immediate pulpal inflammatory reaction in response to tested material found to be statistically significant different between 'Biodentin' and 'MTA' (p=0.001). According to present study Biodentin is found to be more immediate pulpal tissue reactive than MTA when used as a pulp capping material.

Thyroid Hormone Level in Children with Nephrotic Syndrome.

Nephrotic syndrome is the most common glomerular disease affecting children. Hypothyroidism is one of the most important complications which occur due to urinary loss of protein bound thyroid hormones, such as thyroxin binding globulin, transthyretin and albumin. This cross sectional study was conducted in the Department of Pediatric, Mymensingh Medical College Hospital (MMCH), Bangladesh from February 2018 to October 2019. This study was carried out to find out the thyroid profile in children with nephrotic syndrome and compared with thyroid profile of other acute illness in children. Total 122 children aged 2-12 years, further subdivided into Group A (n=61) suffering from nephrotic syndrome (1st attack, infrequent relapse) and Group B (n=61) other disease like viral fever, pneumonia, bronchiolitis, diarrhoea, UTI. Demographic details of patients and their relevant clinical details were obtained by an interviewer administered questionnaire. Blood for free T4, TSH were taken and compared between both groups. The mean FT4 values in Group A and Group B were 16.09±22.32fmol/ml and 68.22±11.65fmol/ml respectively, whereas the TSH level was significantly higher in Group A than controls (5.42±1.04 vs. 3.53±1.44). The T4 levels in nephrotic syndrome (Group A) patients were low. Analysis was done by using SPSS 22.0 version for windows software. Continuous and catagorical parameters were compared by unpaired 't' test and Chi-Square test. A p-value of 0.05 was considered significant. Hypothyroidism was found more in younger children i.e. age less than 6 years. This study concluded that children with nephrotic syndrome have a state of hypothyroidism.

Heavy Metals Accumulation in Vegetables and Its Consequences on Human Health in the Areas Influenced by Industrial Activities.

The degradation of the environment due to numerous industrial practices has emerged as a major issue globally, particularly in a country like Bangladesh. The present study dispenses information about heavy metal (Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb) contamination in some frequently consumed vegetables, namely, ash pumpkin, potato, bitter gourd, buffalo spinach, snake gourd, and pointed gourd grown in an industrially prone location and their repercussion on consumers' health. Proton-induced X-ray emission (PIXE) technique was used as the major analytical tool to detect heavy metal concentrations. Mean concentration and the range of Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb in vegetables were detected (4.81 ± 2.79, 2.43-10.94), (497.57 ± 258.08, 181.24-886.67), (644.49 ± 298.40, 179.56-998.78), (38.88 ± 14.31, 18.88-60.12), (58.11 ± 12.58, 42.55-84.79), (137.24 ± 48.37, 71.99-208.98), (123.31 ± 63.62, 49.97-256.09), (8.09 ± 2.69, 4.29-14.94), and (4.16 ± 2.95, 1.22-9.98) mg/kg (dry weight basis), respectively. An extreme level of heavy metal contamination in vegetable samples was notified regarding the estimated metal pollution index (MPI) and Nemerow pollution index (P) value, which underpinned the health risk values. The estimated hazard index (HI) value stipulated high risk in all varieties of vegetables regardless of age group and cadmium (Cd) was found as the major contributor. Concerning the carcinogenic risk index (CR) for single elements, the value of Co, Ni, and Cr was approximated far above the USEPA threshold risk limit (CR>1E-04). Moreover, total carcinogenic risk (TCR) for all varieties of vegetables exceeded the safety threshold value for both the age group and children, in particular, were found most vulnerable. The outshot of the present study divulged associated health risks for the population group by the heavy metals via dietary intake of vegetables.

Landscape structure influences natural pest suppression in a rice agroecosystem.

Agricultural landscapes are constantly changing as farmers adopt new production practices and respond to changing environmental conditions. Some of these changes alter landscape structure with impacts on natural pest control, pesticide use, and conservation of biodiversity. In rice agroecosystems the effect of landscape structure on natural enemies and pest suppression is often poorly understood. Here we investigate the effect of landscape composition and configuration on a key pest of rice, the brown planthopper (Nilaparvata lugens). Using N. lugens as sentinel prey coupled with predator exclusions, we investigated landscape effects on herbivore suppression and rice grain yield at multiple spatial scales in two regions of Bangladesh. Ladybird beetles and spiders were the most abundant natural enemies of N. lugens with landscape effects observed at all scales on ladybird beetles. Specifically, ladybird beetles were positively influenced by road edges, and fallow land, while spiders were strongly influenced only by rice phenology. Predator exclusion cages showed that N. lugens abundance significantly increased in caged plots, reducing rice gain yield. We also used an estimated biocontrol service index that showed a significant positive relationship with landscape diversity and a significant negative impact on pest density and yield loss. These results suggest that promoting fallow lands and fragmented patches between rice fields could lead to more sustainable insect pest management in rice agroecosystems, potentially reducing the practice of prophylactic insecticide use.

Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice.

Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO). However, tubule cell knockout of KDM6A had relatively minor consequences, characterized by a small reduction in apoptosis, increase in inflammation and downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In proximal tubule lineage HK-2 cells, KDM6A knockdown decreased PPARγ coactivator-1α (PGC-1α) protein levels and mRNA levels of the encoding gene, PPARGC1A. Tubule cell Kdm6a mRNA levels were approximately 2-fold higher in female mice than in male mice, both under sham and UUO conditions. However, kidney fibrosis after UUO was similar in both sexes. The findings demonstrate Kdm6a to be a dynamically regulated gene in the kidney tubule, varying in expression levels by sex and in response to injury. Despite the context-dependent variation in Kdm6a expression, knockout of tubule cell KDM6A has subtle (albeit non-negligible) effects in the adult kidney, at least in males.

Synthesis of New Derivatives of Benzylidinemalononitrile and Ethyl 2-Cyano-3-phenylacrylate: In Silico Anticancer Evaluation.

In this study, microwave-assisted Knoevenagel condensation was used to produce two novel series of derivatives (1-6) from benzylidenemalononitrile and ethyl 2-cyano-3-phenylacrylate. The synthesized compounds were characterized using Fourier transform infrared (FT-IR) and 1H NMR spectroscopies. The pharmacodynamics, toxicity profiles, and biological activities of the compounds were evaluated through an in silico study using prediction of activity spectra for substances (PASS) and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies. According to the PASS prediction results, compounds 1-6 showed greater antineoplastic potency for breast cancer than other types of cancer. Molecular docking was employed to investigate the binding mode and interaction sites of the derivatives (1-6) with three human cancer targets (HER2, EGFR, and human FPPS), and the protein-ligand interactions of these derivatives were compared to those reference standards Tyrphostin 1 (AG9) and Tyrphostin 23 (A23). Compound 3 showed a stronger effect on two cell lines (HER2 and FPPS) than the reference drugs. A 20 ns molecular dynamics (MD) simulation was also conducted to examine the ligand's behavior at the active binding site of the modeled protein, utilizing the lowest docking energy obtained from the molecular docking study. Enthalpies (ΔH), Gibbs free energies (ΔG), entropies (ΔS), and frontier molecular orbital parameters (highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap, hardness, and softness) were calculated to confirm the thermodynamic stability of all derivatives. The consistent results obtained from the in silico studies suggest that compound 3 has potential as a new anticancer and antiparasitic drug. Further research is required to validate its efficacy.

Role of White Blood Cell Count, Immature to Total Ratio and C-Reactive Protein in Early Detection of Clinically Suspected Neonatal Sepsis.

Despite recent advances in neonatal care, early detection of neonatal sepsis still remains challenging. Positive blood culture is the gold standard for definitive diagnosis of neonatal sepsis but is time consuming and demands a well equipped laboratory setting. Therefore, it becomes imperative to evaluate usefulness of white blood cell count, Immature to total (IT) ratio and C-reactive protein as potential markers in the early diagnosis of neonatal sepsis. The objective of the study was to evaluate role of white blood cell count, IT ratio and C-reactive protein in early detection of clinically suspected neonatal sepsis. This cross-sectional descriptive study was conducted from January 2017 to December 2018 at Special Care Newborn Unit (SCANU) of Rangpur Medical College Hospital, Rangpur, Bangladesh. After parental permission and ethical clearance, a total of 70 eligible neonates were included into the study. Estimation of total white blood cell count, IT ratio and C-reactive protein as well as blood culture were done for each case. Significance for Chi-Square test and Pearson's correlation coefficient test was predetermined as p<0.05. Of the total 70 neonates studied, 19(27.14%) were blood culture positive and most common organism was Escherichia coli (7/14, 37.0%). Among individual and combination tests, CRP was highly sensitive (100%) followed by WBC count (74.94%). Highly specific tests in diagnosing sepsis were combination test of IT ratio and CRP (88.23%) followed by combination test of WBC count and CRP (82.35%). Positive predictive value (PPV) was high for combination test of WBC count and CRP (90.90%) followed by combination test of IT ratio and CRP (90.47%). Negative predictive value (NPV) was high in CRP (100.0%) followed by WBC count (89.19%). IT ratio positively correlated with CRP (p=0.002) and there was significant association between raised CRP and WBC count (p=0.005) in neonatal sepsis. Diagnostic role of both individual and combination tests were significant in early detection of clinically suspected neonatal sepsis while awaiting results of blood culture. However, none of the combination tests were able to achieve 100.0% sensitivity.

Study on Myocardial Infarction in Young Adults: Risk Factor Analysis.

Coronary heart disease (CHD) imposes a significant burden on health care systems because of high morbidity and mortality. There is documented evidence that South Asian people develop CHD at a higher rate and at an early age. If the affected individual is 40 years old or below, the tragic consequences are catastrophic. Identifying risk factors could be important for health promotion. The objectives of this study were to determine the frequency of risk factors in young patients with acute myocardial infarction and thus with ischemic heart disease (IHD) aged 40 years and below in our population. It was a descriptive observational study which was carried out at Coronary Care Unit of Rajshahi Medical college Hospital, Rajshahi, Bangladesh in 61 patients from January 2011 to June 2011. All patients who fulfilled the inclusion criteria admitted to coronary care unit (CCU) with a diagnosis of Acute MI were included. Their detailed history was then taken including symptoms at presentation and their risk factors were assessed according to the Framingham Risk Scoring System with the help of history and laboratory investigations. Mean age ±SD of the patients was 36±3.7 year. Most of the patients were male. Smoking was the major risk factor (73.8%) followed by family history of IHD (44.3%). Other risk factors were dyslipidaemia (39.35%), hypertension (37.7%), obesity (11.5%) and diabetes mellitus (8.2%). Majority of the patients were adopted in sedentary lifestyle. 91.8% patient presented with chest pain. Other symptoms were dyspnoea (37.7%), palpitation (59.0%), sweating (77.0%), nausea, vomiting (50.8%) and impaired consciousness (19.7%) etc. Most frequent risk factor for acute myocardial infarction (MI) at young age is smoking followed by family history of MI and dyslipidaemia. Majority of the patients had two or more than two identifiable antecedent risk factors.

Combined application of EPANET and empirical model for possible formation of trihalomethanes in water distribution network of Chattogram city to identify potential carcinogenic health risk zone.

The study identifies potential carcinogenic health risk-zone of Chattogram city for the occurrence of trihalomethanes (THMs) at its water distribution network. The EPANET-THMs simulation model along with an empirical model have been adopted in the study to predict THMs content of supply water of the distribution network of the city's Karnaphuli service area. The empirical model has estimated THMs level of supply water based on influential water quality parameters, and few of these have been used as pre-set values for subsequent EPANET simulation. The simulation (R2= 0.7) shows that THMs' concentrations throughout the network vary from 33 to 486 µg/L. Around 60% of total junctions showed THMs concentrations above 150 µg/L, while that is above 50 µg/L for most (99%) of the junctions. Residual Free chlorine, one of the precursors for the THMs formation in distribution line, has also been simulated by EPANET considering varying applied chlorine dose at the water purification unit and wall (Kw) and bulk (Kb) decay constants. The simulated free residual chlorine peaks are found to be closer to the actual values with chlorine dose of 2 mg/L, and decay constants, Kw = 1 d-1 and Kb = 1 d-1. A mean lifetime total risk of cancer due to the presence of THMs has been found to be very high. Spatial distribution of carcinogenic risk shows that the central zone of the service area is the most vulnerable zone, followed by the western and northern zone. The first ever zone wise risk identification could be used as baseline data for operational and regulatory purposes and may raise awareness among the city's inhabitants. Furthermore, the application of EPANET in combination with an empirical model could be an effective tool for predicting THMs' concentration in water distribution networks in developing countries like Bangladesh to minimize the expenses of measuring THMs.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

BACKGROUND AND PURPOSE: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. EXPERIMENTAL APPROACH: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. KEY RESULTS: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α-smooth muscle actin (α-SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin-angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty-six GPCRs were up-regulated in single Tcf21+ kidney fibroblasts, the most up-regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up-regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α-SMA+ interstitial cells in human kidney samples. CONCLUSION AND IMPLICATIONS: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.

Clinical Profiles and Outcomes of Cytomegalovirus Positive Renal Transplant Patients in Early Post-Transplant Period.

Cytomegalovirus infection can cause increased mortality and morbidity in renal transplant recipient. The purpose of the present study was to observe the clinical profiles and outcomes of Cytomegalovirus positive renal transplant patients in early post-transplant period. This prospective cohort study was conducted in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2016 to August 2017. Adult patients who had undergone renal transplantation were selected as study population. CMV serology (CMV IgM and CMV IgG) of both donor and recipient were detected before renal transplantation. Cytomegalovirus viral DNA was extracted from both serum by using a commercially available DNA extraction kit and PCR was done by the StepOne™ PCR machine using real time PCR kit in all patient during the early post-transplant period. During this period, sign symptoms of patients with cytomegalovirus infection as well as clinical outcomes were also noted. Total number of 32 patients was included in this study with the mean age of 31.15±11.56 years. Cytomegalovirus was found positive in 11(34.4%) patients and negative in 21(65.6%) patients. Anorexia was the most common presentation which was found in 81.8% cases followed by renal impairment, fever, diarrhea, cough and weight loss which were present in 6(54.5%), 3(27.3%), 2(18.2%), 2(18.2%) and 2(18.2%) cases respectively. The outcomes of cytomegalovirus positive patients in first 6 months after renal transplantation revealed 25.0% patients had cytomegalovirus infection; 6.2% patients had cytomegalovirus disease and 6.2% patients were died. However, 9.4% patients had co-infection in the form of UTI and 6.2% patients had re activation of hepatitis C infection associated with cytomegalovirus infection. Cytomegalovirus was found positive in approximately one third of renal transplant recipients in early post-transplant period. Careful clinical evaluation and appropriate laboratory parameters should be looked over for timely diagnosis and management of these cases.

Assessment of the Relationship between Non-motor features and Severity of Parkinson's Disease Patients in Bangladesh.

Parkinson's disease (PD) is second most common neurodegenerative disorder after Alzheimer's disease that may present with both motor and non-motor symptoms (NMSs). Many of the ignored NMSs may potentiate further deterioration of the patient's quality of life (QoL). But there is scarcity of data regarding NMSs of PD patients and their relationship with the disease severity in Bangladesh. This study was aimed to investigate the frequency of NMSs and assess their debatable impact on the severity of PD patients in Bangladesh. This cross-sectional type of observational study was conducted in neurology department of Dhaka Medical College Hospital, Bangladesh from January 2012 to June 2013 which recruited 60 eligible PD patients. The PD patients and disease severity was demonstrated by UK Parkinson's Disease Society Brain Bank criteria for idiopathic PD and the Hoehn and Yahr scale respectively. Whereas, NMSs were demonstrated by the self-structured questionnaire which had encountered 30 common symptoms of PD. The mean age of our study cohort was found 57.88±10.56 years with male female ration 2:1. According to the Hoehn and Yahr (H & Y) severity scale 38.3%, 38.3%, 20.1% and 3.3% patients had been suffering from stage ?, stage II, stage III and stage ?V Parkinson's disease respectively. Irrespective of the severity of the PD the frequency of NMSs was nocturia (66.7%), sadness or blues (65.0%), memory disturbance (61.7%), anxiety (58.3%), insomnia (56.7%), orthostatic hypotension (55.0%), erectile dysfunction (50.0%), urinary urgency (46.7%), anhedonia (45.0%), olfactory disturbance (38.3%), constipation (38.3%), hyper or hypo sexuality (31.7%) and restless leg syndrome (31.7%). However, after head-to-head NMSs analysis, daytime dribbling of saliva (p=0.024), urinary urgency (p=0.036), nocturia (p=0.001), weight loss (p=0.001), anhedonia (p=0.027), excessive daytime sleepiness (p=0.024), insomnia (p=0.007), vivid dream (p=0.024), REM behavior disorder (p=0.010), restless leg syndrome/ periodic leg movements (p=0.043) had significantly been reported higher among the stage II PD patients than that of stage I patients. Whereas fall (p=0.001), dysphagia or choking (p=0.002), constipation (p=0.003), fecal incontinence (p=0.033), excessive daytime sleepiness (p=0.033), anxiety (p=0.036) and anhedonia (p=0.044) were significantly more prevalent among the advanced stage (III) than stage (II) PD patients. Mean total NMS increased significantly with PD severity based on H and Y staging with a mean NMSQ-T (Non-Motor Symptoms Questionnaire Test) of 5.43 in stage 1, 9.22 in stage 2, 13.75 in stage 3 and 17.0 in stage 4 (p=0.0001). This study revealed that there was high frequency of NMSs among the PD patients and most common symptoms were nocturia, sadness, memory impairment, anxiety, insomnia, orthostatic hypotension, erectile dysfunction, anhedonia, urinary urgency and constipation. Finally, the more advanced disease as indicated by a higher H&Y stage was associated with significantly higher number of reported NMSs.

Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.

Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), which posttranslationally modifies its targets through a process termed ISGylation. Cardiac ISG15 is controlled by type I IFN signaling, and ISG15 or ISGylation is upregulated in mice with transverse aortic constriction or infused with angiotensin II; rats with uninephrectomy and DOCA-salt, or pulmonary artery banding; cardiomyocytes exposed to IFNs or CD4+ T cell-conditioned medium; and ventricular tissue of humans with nonischemic cardiomyopathy. By nanoscale liquid chromatography-tandem mass spectrometry, we identified the myofibrillar protein filamin-C as an ISGylation target. ISG15 deficiency preserved cardiac function in mice with transverse aortic constriction and led to improved recovery of mouse hearts ex vivo. Metabolomics revealed that ISG15 regulates cardiac amino acid metabolism, whereas ISG15 deficiency prevented misfolded filamin-C accumulation and induced cardiomyocyte autophagy. In sum, ISG15 upregulation is a feature of pathological ventricular remodeling, and protein ISGylation is an inflammation-induced posttranslational modification that may contribute to heart failure development by altering cardiomyocyte protein turnover.

Hormonal Parameters in Diverse Phenotypes of Polycystic Ovarian Syndrome.

Polycystic ovary syndrome (PCOS) is a polygenic and multifactorial condition, regarded as the most common endocrine abnormality of women in reproductive period. It is commonly assumed that insulin resistance, hyperandrogenism and obesity significantly influence the pathophysiological process of PCOS. This study was designed to estimate hormonal parameters in different phenotypes of PCOS. The cross sectional descriptive type of observational study was carried out at Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2018 to June 2019. Data were collected from purposively selected 107 patients with PCOS by interview, clinical examination and laboratory investigations using a pretested case record form. Data were analyzed by computer software, SPSS-version 22.0. Hormonal parameters in different phenotypes of PCOS were compared with ANOVA test. Phenotype A was found in highest number (59.8%) followed by phenotype B (14.9%), phenotype D (14.0%) and phenotype C (11.2%). Biochemical hyperandrogenism was observed highest in phenotype A (57.8%) followed by phenotype B (36.4%) and phenotype C (6.1%). Biochemical or clinical hyperandrogenism was not observed among patients of phenotype D. Altered LH:FSH ratio was high in phenotype A (14.1%) and Phenotype B (2.8%). Increased serum prolactin level was found highest in phenotype A (10.3%) and increased serum TSH was found highest in phenotype D (4.7%). Statistically significant difference was observed among levels of serum testosterone of different phenotypes (p<0.001). Hormonal derangements among different phenotypes reflect the severity of reproductive dysfunction and metabolic aberrations. Screening for metabolic risks of diverse phenotypes is important to detect and prevent long term health consequences of PCOS.

Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan

Abstract Dengue fever (DF) is increasingly recognized as one of the worlds major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

Glucagon-like Peptide-1 receptor Tie2+ cells are essential for the cardioprotective actions of liraglutide in mice with experimental myocardial infarction.

OBJECTIVES: Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce the rates of major cardiovascular events, including myocardial infarction in people with type 2 diabetes, and decrease infarct size while preserving ventricular function in preclinical studies. Nevertheless, the precise cellular sites of GLP-1R expression that mediate the cardioprotective actions of GLP-1 in the setting of ischemic cardiac injury are uncertain. METHODS: Publicly available single cell RNA sequencing (scRNA-seq) datasets on mouse and human heart cells were analyzed for Glp1r/GLP1R expression. Fluorescent activated cell sorting was used to localize Glp1r expression in cell populations from the mouse heart. The importance of endothelial and hematopoietic cells for the cardioprotective response to liraglutide in the setting of acute myocardial infarction (MI) was determined by inactivating the Glp1r in Tie2+ cell populations. Cardiac gene expression profiles regulated by liraglutide were examined using RNA-seq to interrogate mouse atria and both infarcted and non-infarcted ventricular tissue after acute coronary artery ligation. RESULTS: In mice, cardiac Glp1r mRNA transcripts were exclusively detected in endocardial cells by scRNA-seq. In contrast, analysis of human heart by scRNA-seq localized GLP1R mRNA transcripts to populations of atrial and ventricular cardiomyocytes. Moreover, very low levels of GIPR, GCGR and GLP2R mRNA transcripts were detected in the human heart. Cell sorting and RNA analyses detected cardiac Glp1r expression in endothelial cells (ECs) within the atria and ventricle in the ischemic and non-ischemic mouse heart. Transcriptional responses to liraglutide administration were not evident in wild type mouse ventricles following acute MI, however liraglutide differentially regulated genes important for inflammation, cardiac repair, cell proliferation, and angiogenesis in the left atrium, while reducing circulating levels of IL-6 and KC/GRO within hours of acute MI. Inactivation of the Glp1r within the Tie2+ cell expression domain encompassing ECs revealed normal cardiac structure and function, glucose homeostasis and body weight in Glp1rTie2-/- mice. Nevertheless, the cardioprotective actions of liraglutide to reduce infarct size, augment ejection fraction, and improve survival after experimental myocardial infarction (MI), were attenuated in Glp1rTie2-/- mice. CONCLUSIONS: These findings identify the importance of the murine Tie2+ endothelial cell GLP-1R as a target for the cardioprotective actions of GLP-1R agonists and support the importance of the atrial and ventricular endocardial GLP-1R as key sites of GLP-1 action in the ischemic mouse heart. Hitherto unexplored species-specific differences in cardiac GLP-1R expression challenge the exclusive use of mouse models for understanding the mechanisms of GLP-1 action in the normal and ischemic human heart.

Carbon dioxide and light curves and leaf gas exchange responses to shade levels in bell pepper (Capsicum annuum L.).

Vegetable crops grown under shade nets typically show increased yield and quality. However, little is known about the photosynthetic responses at various CO2 and light levels under nets. This study aimed to determine carbon dioxide (A/Cc) and light (A/I) curves and leaf gas exchange response of bell pepper plants grown under nets at various shade levels. Experiments were conducted in the spring-summer of 2016 and 2018 in Tifton, Georgia (GA), USA, with five shade treatments [0 % (open field), 30 %, 47 %, 63 %, and 80 %]. The A/Cc curves revealed that plants grown at 30 % shade and in the open field had similar carboxylation, electron transport, and triose phosphate utilization rates. The A/I curves showed that gross and net photosynthesis were highest at 30 % shade. The 30 % shade had similar stomatal conductance, intercellular CO2, electron transport rate, and water use efficiency compared to the open field. The A/Cc and A/I curves and the leaf gas exchange parameters explained the intrinsic causes for the higher net photosynthesis at 30 % shade than in open-field bell pepper. The information from A/Cc-curves, A/I-curves, and leaf gas exchange is applicable in modeling photosynthesis and predicting primary productivity for C3 plants in elevated-CO2 and altered-light environments.

Inhibitor-Induced Wavetrains and Spiral Waves in an Extended FitzHugh-Nagumo Model of Nerve Cell Dynamics.

It is well known that the FitzHugh-Nagumo model is one of the simplified forms of the four-variable Hodgkin-Huxley model that can reflect most of the significant phenomena of nerve cell action potential. However, this model cannot capture the irregular action potentials of sufficiently large periods in a one-parameter family of solutions. Motivated by this, we propose a modified FitzHugh-Nagumo reaction-diffusion system by changing its recovery kinetics. First, we investigate the parameter regime to know the existence of the wavetrains. Second, we conceive the occurrence of Eckhaus bifurcations of solutions that divide the solution region into two parts. The essential spectra at different grid points explore the occurrence of bifurcations of the waves. We find that the wavetrains of sufficiently large periods cross the stability boundary. This characteristic phenomenon is absent in the standard FitzHugh-Nagumo model. Finally, we observe a reasonable agreement between the direct PDE simulations and the solutions in the traveling wave ODEs. Furthermore, the model exhibits spiral wave for monotone and non-monotone cases that agrees with the waves observed in cellular activity.

Clinical Profile and Immediate Outcome of Pyogenic Meningitis in Children.

Meningitis literally means inflammation of the meninges. It is mostly caused by bacteria, virus, fungus and protozoa and pyogenic meningitis constitutes a serious neurological disorder associated with significant morbidity and mortality in developing countries. This study was carried out to evaluate the clinical presentation and immediate outcome of pyogenic meningitis in children. This was a prospective observational study and conducted at department of Paeditrics in Cumilla Medical College Hospital, Cumilla, Bangladesh from July 2014 to June 2015. Total 50 children were diagnosed as pyogenic meningitis fulfilling the inclusion criteria was included in this study. Cases were enrolled purposively. Immediately after admission through history and clinical examination, complete blood count, random blood sugar, Cerebrospinal fluid (CSF) examination and blood culture was done in all patients. For statistical analysis chi-square test was done and significance of analysis was made when p value <0.05. This study includes patients aged between 2 months to 12 years and male female ratio was 1.5:1. Several risk factors like male sex (60.0%), age below one year (42.0%), Protein energy malnutrition (PEM) (30.0%), not exclusively breastfed (44.0%) were identified. Common presenting complaints were fever (100.0%), convulsion (96.0%), altered consciousness (42.0%) and vomiting (38.0%). Common physical signs were neck rigidity (56.0%), Kernig's sign (26.0%) and bulged fontanelle (34.0%). CSF was hazy in 54.0%, clear in 38.0% and turbid in 08.0% cases, CSF protein was more than 100mg/dl in 90.0% of the cases and glucose was less than 40mg/dl in most of the cases (94.0%). Streptococcus Pneumoniae (49.0%) followed by Neisseria Meningitidis (38.0%) were the two most commonly isolated organism responsible for pyogenic meningitis. Mortality rate during hospital stay was 18.0% and complications developed in 18.0% of cases. To avoid maltreatment in our resource limited setting due to failure of identifying organism, this study might help to administer appropriate antibiotics against organism and to reduce morbidity and mortality in meningitis. This study revealed less mortality rate in our country than neighbors and severe malnutrition important risk factors for the burden of pyogenic meningitis. It requires large scale multicentre studies to establish the whole scenario of Bangladesh.