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Background: Dislocation of the acromioclavicular joint (ACJ), accounting for 9%-12% of all shoulder injuries, is a frequent shoulder problem. Clavicular hook plates have proven to be a successful implant choice for surgical management. The benefit of this method is that it preserves the diarthrosis of the ACJ while reducing dislocation. Positive outcomes with this approach have been reported., Objective: This study aimed to quantify functional recovery using the Constant Murley Score (CMS) in patients with ACJ dislocations treated with a clavicle hook plate., Methodology: The retrospective study was conducted at the orthopedic department of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan, for over one year, from January 20, 2021, to 19 January, 2022. A total of 40 individuals were identified who were operated on for acute ACJ dislocation with hook plates in the department and were included in the research. All patients underwent open reduction and internal fixation with a clavicular hook plate, which was usually removed three months after surgery. The functional outcome was evaluated using the CMS on the day before plate removal, three months after plate removal, and six months following surgery., Results: Of the participants, 28 (70%) were male, and 12 (30%) were female. The mean CMS was 72.25 ± 3.95 (satisfactory) at 24 weeks and 90.45 ± 1.9 (excellent) eight weeks after the removal of the plate., Conclusion: The hook plate is an excellent choice for treating acute ACJ dislocation. Radiographic and functional assessments indicate that these plates provide good outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mannan et al.)

Motivation: Integrating multiple omics datasets can significantly advance our understanding of disease mechanisms, physiology, and treatment responses. However, a major challenge in multi-omics studies is the disparity in sample sizes across different datasets, which can introduce bias and reduce statistical power. To address this issue, we propose a novel framework, OmicsNMF, designed to impute missing omics data and enhance disease phenotype prediction. OmicsNMF integrates Generative Adversarial Networks (GANs) with Non-Negative Matrix Factorization (NMF). NMF is a well-established method for uncovering underlying patterns in omics data, while GANs enhance the imputation process by generating realistic data samples. This synergy aims to more effectively address sample size disparity, thereby improving data integration and prediction accuracy., Results: For evaluation, we focused on predicting breast cancer subtypes using the imputed data generated by our proposed framework, OmicsNMF. Our results indicate that OmicsNMF consistently outperforms baseline methods. We further assessed the quality of the imputed data through survival analysis, revealing that the imputed omics profiles provide significant prognostic power for both overall survival and disease-free status. Overall, OmicsNMF effectively leverages GANs and NMF to impute missing samples while preserving key biological features. This approach shows potential for advancing precision oncology by improving data integration and analysis., Availability and Implementation: Source code is available at: https://github.com/compbiolabucf/OmicsNMF., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The tibia, a crucial long bone in the lower leg, plays a vital role in supporting mobility. Distal tibial fractures (DTFs) are relatively uncommon among lower extremity fractures. Minimally invasive percutaneous plate osteosynthesis (MIPPO) has become increasingly popular due to advancements in surgical techniques and its potential for positive clinical outcomes., Objective: To evaluate the functional outcomes and complication rates of closed DTFs treated with MIPPO in adult patients, and to assess the impact of factors such as age, injury mechanism, and fracture classification on the treatment results., Methodology: A retrospective study was conducted in the Department of Orthopedic Surgery at Sheikh Zayed Medical College Rahim Yar Khan, Pakistan from January 1, 2022, to December 31, 2022. Seventy patients, aged 18 to 60 years, were included. Postoperative follow-up assessments were conducted at six weeks, three months, and six months to evaluate functional outcomes., Results: The majority of patients were male, with a mean age of 34 years. The most frequent cause of injury was road traffic accidents, followed by falls from height and other causes. Fractures were classified into three types: A1, A2, and A3. Functional outcomes at the final follow-up showed most patients had excellent to satisfactory results, while a smaller proportion had fair to poor outcomes. A few patients experienced postoperative complications, including malunion, infection, and ankle stiffness., Conclusion: The study suggests that MIPPO is an effective surgical technique for managing DTFs, providing favourable functional outcomes with a relatively low complication rate. Therefore, MIPPO can be considered a valuable option in treating these fractures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Sheikh Zayed Medical College Rahim Yar Khan issued approval 149/ERB/SZMC. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mannan et al.)

The heterogeneous pediatric populations, their physiological differences, along with the necessity of performing additional dose calculation, make the pediatric population more vulnerable to the incidences of inappropriate antibiotic doses. This study was conducted to examine and evaluate the appropriateness of antibiotic doses. A cross-sectional study with a quantitative approach was conducted in three hospitals located in Savar from January 06, 2021 to October 17, 2022. This study had used a convenient sampling method to collect 405 filled prescription orders from heterogeneous pediatric patients prescribed by physicians from emergency, inpatient, and outpatient care units of various clinical settings. The Harriet Lane Handbook was used as reference to investigate inappropriate doses of antibiotics. Subsequently, all analyses were conducted using the RStudio 1.3.959 software. Binary logistic regression was used to assess the risk of inappropriate antibiotic prescription in pediatrics. The overall prevalence of inappropriate antibiotic dosing in pediatrics was 335 out of 545 (61.5%). Overdosing (36.3%) and oral antibiotic prescriptions (64%) were more common than underdosing (20.4%) and parenteral antibiotics (36%). The majority (230 out of 405, 56.8%) of pediatric patients had prescriptions with inappropriate antibiotic doses, with prevalence rates of 33.8% for inpatients, 86.7% for outpatients, and 50% for emergency pediatrics. The results also indicated that pediatric patients in outdoor and emergency care units, infants, toddlers, and early childhood, those prescribed two antibiotics simultaneously, and those receiving parenteral antibiotics, were less likely to have inappropriate antibiotic dosages in their prescriptions. This study demonstrated that about one out of every two prescriptions had inappropriate antibiotic doses; in particular, prescriptions containing only one antibiotic exhibited a substantial proportion of inappropriate antibiotic doses. Inappropriate antibiotic doses may result in therapeutic failure, patient harm, and antibiotic resistance. Good clinical pharmacy practice and careful adherence to pediatric dosing standards may minimize inappropriate antibiotic doses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mahmudul Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Motivation: The identification and understanding of drug-target interactions (DTIs) play a pivotal role in the drug discovery and development process. Sequence representations of drugs and proteins in computational model offer advantages such as their widespread availability, easier input quality control, and reduced computational resource requirements. These make them an efficient and accessible tools for various computational biology and drug discovery applications. Many sequence-based DTI prediction methods have been developed over the years. Despite the advancement in methodology, cold start DTI prediction involving unknown drug or protein remains a challenging task, particularly for sequence-based models. Introducing DTI-LM, a novel framework leveraging advanced pretrained language models, we harness their exceptional context-capturing abilities along with neighborhood information to predict DTIs. DTI-LM is specifically designed to rely solely on sequence representations for drugs and proteins, aiming to bridge the gap between warm start and cold start predictions., Results: Large-scale experiments on four datasets show that DTI-LM can achieve state-of-the-art performance on DTI predictions. Notably, it excels in overcoming the common challenges faced by sequence-based models in cold start predictions for proteins, yielding impressive results. The incorporation of neighborhood information through a graph attention network further enhances prediction accuracy. Nevertheless, a disparity persists between cold start predictions for proteins and drugs. A detailed examination of DTI-LM reveals that language models exhibit contrasting capabilities in capturing similarities between drugs and proteins., Availability and Implementation: Source code is available at: https://github.com/compbiolabucf/DTI-LM., (© The Author(s) 2024. Published by Oxford University Press.)

The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand. In order to test the hypothesis, we designed an array of mismatched target sites at the PAM distal end and performed in vitro and cell line-based experiments, which showed a strong correlation for Cas9 activity. We found that target sites having multiple mismatches in the 18th to 15th position upstream of the PAM showed no to little activity. For further mechanistic validation, Molecular Dynamics simulations were performed, which revealed that certain mismatches showed elevated root mean square deviation values that can be attributed to conformational instability within the RNA-DNA duplex. Therefore, for successful prediction of the off-target effect of SpCas9, along with complementation-derived energy, the RNA-DNA duplex stability should be taken into account., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, 1,4-benzothiazine-based bisamide derivatives, a new class of antibacterial agents targeting bacterial peptide deformylase (PDF), were designed and synthesized to combat Staphylococcus aureus infection. Molecular modeling of the designed molecules showed better docking scores compared to the natural product actinonin. Bioactivity assessment identified two derivatives with promising antibacterial activity in vitro . The stability of the most active molecule, 8bE , was assessed using molecular dynamics (MD) simulation. Significantly, compound 8bE could also inhibit the S. aureus biofilm at low concentrations. Furthermore, the capability of the synthesized molecule to inhibit S. aureus biofilm formation on medical devices like urinary catheters is also demonstrated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Naithani, Das, Ushare, Nath, Biswas, Kundu, Ahmed, Mohan and Bhowmik.)

Background: Disability-free life expectancy (DFLE) has been used to gain a better understanding of the population's quality of life., Objectives: The authors aimed to estimate age and sex-specific disability-free life expectancy (DFLE) for urban and rural areas of Bangladesh, as well as to investigate the differences in DFLE between males and females of urban and rural areas., Methods: Data from the Bangladesh Sample Vital Statistics-2016 and the Bangladesh Household Income and Expenditure Survey (HIES)-2016 were used to calculate the disability-free life expectancy (DFLE) of urban and rural males and females in Bangladesh in 2016. The DFLE was calculated using the Sullivan method., Results: With only a few exceptions, rural areas have higher mortality and disability rates than urban areas. For both males and females, statistically significant differences in DFLE were reported between urban and rural areas between the ages of birth and 39 years. In comparison to rural males and females, urban males and females had a longer life expectancy (LE), a longer disability-free life expectancy, and a higher share of life without disability., Conclusion: This study illuminates stark urban-rural disparities in LE and DFLE, especially among individuals aged < 1-39 years. Gender dynamics reveal longer life expectancy but shorter disability-free life expectancy for Bangladeshi women compared to men, emphasizing the need for targeted interventions to address these pronounced health inequalities., (© 2024. The Author(s).)

Objective: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications., Summary Background Data: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level., Methods: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes., Results: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications., Conclusion: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents., Methods: A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed., Results: Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (β = 0.10, p = 0.001), higher education (College: β = 0.09, p = 0.025; Bachelor: β = 0.22, p<0.001; Master or above: β = 0.14, p<0.001), various professions (student: β = 0.57, p<0.001; housewife: β = 0.33, p<0.001; employee: β = 0.53, p<0.001; businessman: β = 0.31, p<0.001; unemployed: β = 0.15, p<0.001), and residing in semi-urban (β = 0.32, p<0.001) or urban areas (β = 0.15, p<0.001). Positive predictors for attitudes included being married (β = 0.18, p<0.001), specific professions (student: β = 1.06, p<0.001; housewife: β = 0.33, p<0.001; employee: β = 0.86, p<0.001; businessman: β = 0.37, p<0.001; unemployed: β = 0.47, p<0.001), higher SES (Lower-middle: β = 0.22, p<0.001; Middle: β = 0.26, p<0.001), and residing in semi-urban areas (β = 0.18, p<0.001); negative predictors included higher education (College: β = -0.12, p = 0.001; Master or above: β = -0.09, p = 0.008) and being rich (β = -0.13, p<0.001). Positive predictors for practices included being married (β = 0.18, p<0.001), specific professions (student: β = 0.32, p<0.001; employee: β = 0.43, p<0.001; businessman: β = 10, p = 0.034; unemployed: β = 0.11, p = 0.009), and higher SES (Lower-middle: β = 0.14, p = 0.009; Middle: β = 0.38, p<0.001; Higher-middle: β = 0.15, p = 0.008); negative predictors included higher education (College: β = -0.21, p<0.001), being rich (β = -0.12, p<0.001), residing in semi-urban (β = -0.14, p<0.001) or urban areas (β = -0.16, p<0.001)., Conclusions: Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Raihan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Molecular self-assembly assisted self-healing supramolecular metallogels of azelaic acid with cobalt(II)-, nickel(II)-, and zinc(II)-based metal acetate salts were successfully fabricated. Individually, N , N '-dimethylformamide and dimethyl sulfoxide were immobilized within these distinctly synthesized soft-scaffolds of metallogels to attain their semisolid viscoelastic nature. Rheological experiments such as amplitude sweep, frequency sweep, and thixotropic measurements were executed for these metallogels to ratify their gel features. The different extents of supramolecular interactions operating within these solvent-directed metallogels were clearly reflected in terms of their distinct morphological patterns as investigated through field emission scanning electron microscopy. Comparative infrared (IR) spectral properties of metallogels along with individual metal salts and azelaic acid were analyzed. These experimental data clearly depict the significant shifting of Fourier transform (FT)-IR peaks of xerogel samples of different metallogels from the gel-forming precursors. The networks present within the soft-scaffold are evidently illustrated by the electrospray ionization-mass experimental data. The temperature-dependent ionic conductivity studies with these solvent-directed versatile metallogel systems were investigated through impedance spectroscopy. The temperature-dependent impedance spectroscopic studies clearly demonstrate that the ion-transportation within the gel matrix depends not only on the types of cations but also on the dielectric properties of the immobilized solvents. The antipathogenic effect of these metallogel systems has also been explored by testing their effectiveness against human pathogenic Gram-negative bacteria Klebsiella pneumoniae (MTCC 109) and Vibrio parahemolyticus , and Gram-positive bacteria like Bacillus cereus (MTCC 1272). These gel soft-scaffolds show no significant cytotoxicity against both the human neuroblastoma cell line-SH-SY5Y and the human embryonic kidney cell line-HEK 293.

Objective: To examine the height-for-age z-score (HAZ) of 0-35 months' children along with stunting prevalence to identify trends, changes and available nutrition-sensitive and specific determinants that could help explain the long-term variation in child linear growth using successive Bangladesh Demographic and Health Surveys (BDHS) data from 1996 to 2018., Design: The BDHS pooled data are used for determining the key outcome variables HAZ, stunting and severe stunting. Trends, kernel-weighted local polynomial smoothing illustrations, pooled multivariable linear probability model (LPM), ordinary least squares method (OLS) and regression decomposition were used., Participants: Mothers having 0-35 months' children, the most critical age range for growth faltering., Results: The mean HAZ increased by 0·91(±1·53) with 0·041 annual average change, while the percentages of stunting (-26·63 ± 0·54) and severe stunting (-21·12 ± 0·48) showed a reduction with 1·21 and 0·96 average annual changes, respectively. The average HAZ improvement (0·42 ± 1·56) in urban areas was less than the rural areas (1·16 ± 1·44). Similar patterns followed for stunting and severe stunting. The prenatal doctor visits (3064·65 %), birth in a medical facility (1054·32 %), breastfeeding initiation (153·18 %) and asset index (144·73 %) demonstrated a huge change. The findings of OLS, LPM and regression decomposition identified asset index, birth order, paternal and maternal education, bottle-fed, prenatal doctor visit, birth in a medical facility, vaccination, maternal BMI and ever-breastfed as influencing factors to predict the long-term changes of stunting and severe stunting., Conclusion: The nutrition-sensitive and specific factors identified through regression decomposition describing long-term variation in child linear growth should be focused further to attain the sustainable development goals.

Background: Dietary diversity is a key determinant of infant and young child eating patterns for a variety of food groups taken by children between the ages of 6-23 months. The study aimed to examine the association between prenatal and postnatal obstetric care factors of mother and child's dietary diversity, and specific food practices in Bangladesh., Methods: This study analyzed the data of 2497 children between the age of 6-23 extracted from the latest countrywide Bangladesh Demographic Health Survey 2017-2018 and explored relationships between prenatal and postnatal obstetric care received by mother and dietary diversity score (DDS), minimum dietary diversity (MDD), and introduction of solid, semi-solid, and soft foods (ISSSF) of their children., Results: Findings revealed that ≥ 4 antenatal care (ANC) visits care visits increased the DDS (adjusted [Formula: see text]: 0.32, 95% CI [0.21, 0.43]), increased the likelihood of MDD (AOR 1.54, 95% CI [1.23, 1.93]), and ISSSF (AOR 1.24, 95% CI [1.08, 1.48]), consuming eggs (AOR 1.47, 95% CI [1.23, 1.76]), and vitamin A vegetables and fruits (AOR 1.38, 95% CI [1.15, 1.66]). Moreover, DDS (adjusted β: 0.05, 95% CI [0.00, 0.11]) and MDD (AOR 1.66, 95% CI [1.31, 2.11]) are linked to childbirth in a medical facility. The C-section delivery influences the DDS (adjusted [Formula: see text]: 0.05, 95% CI [0.00, 0.10]), MDD (AOR 1.39, 95% CI [1.10, 1.75]), and ISSSF (AOR 1.22, 95% CI [1.02, 1.48]). Besides, postnatal visits within 48 h of delivery linked to MDD (AOR 0.66, 95% CI [0.49, 0.89]) and ISSSF (AOR 0.76, 95% CI [0.59, 0.97]), and physicians or professionals providing postnatal checkups were significantly associated with DDS (adjusted [Formula: see text]: 0.09, 95% CI [0.02, 0.16]), MDD (AOR 1.69, 95% CI [1.26, 2.26]), and ISSSF (AOR 1.30, 95% CI [1.04, 1.62])., Conclusion: Knowledge of child nutritional feeding should emphasize during prenatal and postnatal obstetric care of mother, particularly during antenatal and postnatal visits, C-section delivery, and birth in a healthcare facility to eradicate malnutrition and establish healthy child feeding practices., (© 2023. The Author(s).)

Background: This research focuses on the positive impacts of the COVID-19 lockdown on society and the environment, despite acknowledging the widespread negative effects of the pandemic and lockdown measures. The research was aimed at pinpointing and evaluating the beneficial results stemming from these measures., Method: Data for the study was collected through an online survey distributed via Google forms to adults over the age of 18 across the country. A total of 1230 participants completed the survey, mostly from rural areas (61.7%), providing valuable insights for analysis. The questionnaire encompassed personal, family, and cohesive social data, along with information on the environment and biodiversity. The study utilized structural equation modeling (SEM) and confirmatory factor analysis (CFA) to analyze the data and examine correlations between variables., Results: The findings indicated that the COVID-19 lockdown had positive implications for individuals and society, leading to increased health consciousness, improved family relationships, and constructive social attitudes. Moreover, restrictions on access to natural tourist destinations and parks during the lockdown contributed to positive changes in biodiversity. These results highlight the importance of adopting appropriate measures during pandemics to foster personal and social well-being, as well as the preservation of natural environments and biodiversity., Conclusion: This study emphasizes the need for further research to promote sustainable living in similar situations. By understanding the data appropriately, individuals can play a constructive role in future pandemics, leading to positive outcomes for both society and the environment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: The associated factors and patterns of giving birth in home settings of rural areas have been extensively studied in Bangladeshi literature. However, urban areas still need to be explored, particularly with recent data. Therefore, the authors aimed to investigate the influential determinants of delivery at home in urban areas of Bangladesh., Materials and Methods: In this study, 1699 urban-dwelling women who had given birth within the previous 60 months of the survey and lived in urban areas were used. The secondary data were extracted from the latest Bangladesh Demographic and Health Survey 2017-2018. Descriptive statistics and logistic regression were applied along with the association among selected variables were examined by the Chi-square test., Results: Findings depict that 36.49% of women who lived in urban areas of Bangladesh delivered at home, whereas, 63.51% delivered at different govt. and private health care facilities. Women who lived in Chittagong [adjusted odds ratio (AOR) = 2.11, 95% CI 1.24-3.60], Barisal [AOR = 2.05, 95% CI 1.16-3.64] and Sylhet [AOR = 1.92, 95% CI 1.08-3.43] divisions have more likelihood to deliver at home (36.85%). Urban women following Christian religion [AOR = 10.71, 95% CI 1.32-86.68] have higher odds of delivering child at home (0.47%). Urban women having three or more children before her latest delivery (22.37%) and who are employed (29.37%) have more likelihood to deliver at home. However, women aged between 25 and 34 years (43.50%), who have higher education (25.90%), play the role of household head (9.06%), have parity of more than two births (2.24%), and read daily newspapers (68.69%) had a lower chance of delivery at home. Furthermore, women from wealthier families (89.12%) and more antenatal care (ANC) visits (94.93%) were less likely to have a delivery at home., Conclusion: Despite significant progress in women and reproductive health in Bangladesh, the proportion of delivery in the home in urban areas is alarming and should be emphasized more. The authors believe the identified factors will help design interventions and policy development on this issue., (© 2023. BioMed Central Ltd., part of Springer Nature.)

PHPT1 is a protein histidine phosphatase that has been implicated in several disease pathways, but the chemical tools necessary to study the biological roles of this enzyme and investigate its utility as a therapeutic target have yet to be developed. To this end, the discovery of PHPT1 inhibitors is an area of significant interest. Here, we report an investigation of illudalic acid and illudalic acid analog-based inhibition of PHPT1 activity. Four of the seven analogs investigated had IC 50 values below 5 μM, with the most potent compound (IA1-8H2) exhibiting an IC 50 value of 3.4±0.7 μM. Interestingly, these compounds appear to be non-covalent, non-competitive inhibitors of PHPT1 activity, in contrast to other recently reported PHPT1 inhibitors. Mutating the three cysteine residues to alanine has no effect on inhibition, indicating that cysteine is not critical for interactions between inhibitor and enzyme., (© 2023 Wiley-VCH GmbH.)

The importance of three synthesized metallogels of suberic acid distinctly with nickel, zinc, and cadmium acetate salts has been uncovered. For the creation of these soft materials, N , N '-dimethyl formamide was utilized as a source of the trapped solvent. The synthesized metallogels display intriguing viscoelasticity, and the interpretation of experimental parameters obtained from rheological results advocates the gel behavior. Microstructural analysis combined with energy-dispersive X-ray confirms the occurrence of individual gel-developing constituents as observed in different hierarchical microstructural patterns. Significant variations in microstructural arrangements with diverse extent of supramolecular non-covalent patterns inside gel networks were perceived through field emission scanning electron microscopy, atomic force microscopy, and transmission electron microscopy analyses. Fourier transform infrared and electrospray ionization-mass spectral analyses and powder X-ray diffraction analysis of metallogel samples of different gel-establishing ingredients help to investigate the possible supramolecular interactions dictating the metallogel scaffolds. Thermogravimetric analysis of xerogel samples was collected from the synthesized metallogels to understand the thermal stability. These gel materials were characterized by their potential antibacterial efficiency. The potency of metallogels against selective Gram-positive and Gram-negative bacteria was visualized via a spectrophotometer. Human pathogens like Klebsiella pneumoniae (MTCC 109), Salmonella typhi (MTCC 733), Vibrio parahaemolyticus , Bacillus cereus (MTCC 1272), Lactobacillus fermentum (NCDO 955), and Staphylococcus aureus (MTCC 96) are employed in this study. Apart from the biological significance, our metallogels demonstrate as incredible diode performance of fabricated semiconducting systems, which exhibit a considerable amount of non-linearity demonstrating a non-ohmic conduction mechanism at room temperature in dark conditions. Device fabrication was achieved from these metallogels employing the sandwich model with indium tin oxide-coated glass substrates/metallogel/Al structure.

Chronic airway illness is a well-documented inhalation injury side effect. Many pulmonary function impairments persisted for several months after lung parenchymal injury. Thus, the purpose of this study was to investigate the effects of inspiratory muscle training on respiratory muscle strength and pulmonary function (PFT) in patients who had suffered an inhalation injury. This study included male patients with inhalation injuries aged 20-35 years. Patients were chosen at random and assigned to an exercise group, which received inspiratory muscle training and routine chest physiotherapy, including early ambulation, coughing, and deep breathing, three times weekly for 4 weeks, and the control group, which only received routine chest physiotherapy. All participants were assessed for PFT and respiratory muscle strength at enrollment and the end of the study. The statistical analysis for outcome variables between both groups revealed no significant differences before treatment (P > .05) of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximal inspiratory pressure, and maximal expiratory pressure. According to the findings of this study, including IMT as part of a physical therapy program led to significant gains (P ˂ .05) in FVC and FEV1. However, after treatment, there was not a substantial difference found in either the MIP or the MEP between the groups. The exercise group performed better in terms of FVC, FEV1, MIP, and MEP after receiving treatment, according to these significant and non-significant differences., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Of the three primary cannabinoids in cannabis: Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), cannabidiol (CBD) and cannabinol (CBN), very little is known about the actions of CBN, the primary oxidative metabolite of THC. Our goal was to determine if CBN exposure during gastrulation alters embryonic development, and if so, does it act via the canonical cannabinoid receptors. Zebrafish embryos were exposed to CBN during gastrulation and exhibited dose-dependent malformations, increased mortality, decreased locomotion and a reduction in motor neuron branching. Moreover, larva showed a significant reduction in the response to sound stimuli. CBN exposure altered the development of hair cells associated with otic vesicles and the lateral line. Pharmacological block of Cb2rs with AM 630 or JTE 907 prevented many of the CBN-induced developmental defects, while block of Cb1rs with AM 251 or CP 945598 had little or no effect. Altogether we show that embryonic exposure to CBN results in alterations in embryonic growth, neuronal and hair cell development, physiology and behavior via Cb2r-mediated mechanisms., (© 2022. The Author(s).)

Background: The eukaryotic genome is capable of producing multiple isoforms from a gene by alternative polyadenylation (APA) during pre-mRNA processing. APA in the 3'-untranslated region (3'-UTR) of mRNA produces transcripts with shorter or longer 3'-UTR. Often, 3'-UTR serves as a binding platform for microRNAs and RNA-binding proteins, which affect the fate of the mRNA transcript. Thus, 3'-UTR APA is known to modulate translation and provides a mean to regulate gene expression at the post-transcriptional level. Current bioinformatics pipelines have limited capability in profiling 3'-UTR APA events due to incomplete annotations and a low-resolution analyzing power: widely available bioinformatics pipelines do not reference actionable polyadenylation (cleavage) sites but simulate 3'-UTR APA only using RNA-seq read coverage, causing false positive identifications. To overcome these limitations, we developed APA-Scan, a robust program that identifies 3'-UTR APA events and visualizes the RNA-seq short-read coverage with gene annotations., Methods: APA-Scan utilizes either predicted or experimentally validated actionable polyadenylation signals as a reference for polyadenylation sites and calculates the quantity of long and short 3'-UTR transcripts in the RNA-seq data. APA-Scan works in three major steps: (i) calculate the read coverage of the 3'-UTR regions of genes; (ii) identify the potential APA sites and evaluate the significance of the events among two biological conditions; (iii) graphical representation of user specific event with 3'-UTR annotation and read coverage on the 3'-UTR regions. APA-Scan is implemented in Python3. Source code and a comprehensive user's manual are freely available at https://github.com/compbiolabucf/APA-Scan ., Result: APA-Scan was applied to both simulated and real RNA-seq datasets and compared with two widely used baselines DaPars and APAtrap. In simulation APA-Scan significantly improved the accuracy of 3'-UTR APA identification compared to the other baselines. The performance of APA-Scan was also validated by 3'-end-seq data and qPCR on mouse embryonic fibroblast cells. The experiments confirm that APA-Scan can detect unannotated 3'-UTR APA events and improve genome annotation., Conclusion: APA-Scan is a comprehensive computational pipeline to detect transcriptome-wide 3'-UTR APA events. The pipeline integrates both RNA-seq and 3'-end-seq data information and can efficiently identify the significant events with a high-resolution short reads coverage plots., (© 2022. The Author(s).)

The use of high-throughput omics technologies is becoming increasingly popular in all facets of biomedical science. The mRNA sequencing (RNA-seq) method reports quantitative measures of more than tens of thousands of biological features. It provides a more comprehensive molecular perspective of studied cancer mechanisms compared to traditional approaches. Graph-based learning models have been proposed to learn important hidden representations from gene expression data and network structure to improve cancer outcome prediction, patient stratification, and cell clustering. However, these graph-based methods cannot rank the importance of the different neighbors for a particular sample in the downstream cancer subtype analyses. In this study, we introduce omicsGAT, a graph attention network (GAT) model to integrate graph-based learning with an attention mechanism for RNA-seq data analysis. The multi-head attention mechanism in omicsGAT can more effectively secure information of a particular sample by assigning different attention coefficients to its neighbors. Comprehensive experiments on The Cancer Genome Atlas (TCGA) breast cancer and bladder cancer bulk RNA-seq data and two single-cell RNA-seq datasets validate that (1) the proposed model can effectively integrate neighborhood information of a sample and learn an embedding vector to improve disease phenotype prediction, cancer patient stratification, and cell clustering of the sample and (2) the attention matrix generated from the multi-head attention coefficients provides more useful information compared to the sample correlation-based adjacency matrix. From the results, we can conclude that some neighbors play a more important role than others in cancer subtype analyses of a particular sample based on the attention coefficient.

Motivation: Time-lapse microscopy is a powerful technique that relies on images of live cells cultured ex vivo that are captured at regular intervals of time to describe and quantify their behavior under certain experimental conditions. This imaging method has great potential in advancing the field of precision oncology by quantifying the response of cancer cells to various therapies and identifying the most efficacious treatment for a given patient. Digital image processing algorithms developed so far require high-resolution images involving very few cells originating from homogeneous cell line populations. We propose a novel framework that tracks cancer cells to capture their behavior and quantify cell viability to inform clinical decisions in a high-throughput manner., Results: The brightfield microscopy images a large number of patient-derived cells in an ex vivo reconstruction of the tumor microenvironment treated with 31 drugs for up to 6 days. We developed a robust and user-friendly pipeline CancerCellTracker that detects cells in co-culture, tracks these cells across time and identifies cell death events using changes in cell attributes. We validated our computational pipeline by comparing the timing of cell death estimates by CancerCellTracker from brightfield images and a fluorescent channel featuring ethidium homodimer. We benchmarked our results using a state-of-the-art algorithm implemented in ImageJ and previously published in the literature. We highlighted CancerCellTracker's efficiency in estimating the percentage of live cells in the presence of bone marrow stromal cells., Availability and Implementation: https://github.com/compbiolabucf/CancerCellTracker., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fast excitatory synaptic transmission in the CNS is mediated by the neurotransmitter glutamate, binding to and activating AMPA receptors (AMPARs). AMPARs are known to interact with auxiliary proteins that modulate their behavior. One such family of proteins is the transmembrane AMPAR-related proteins, known as TARPs. Little is known about the role of TARPs during development or about their function in nonmammalian organisms. Here, we report on the presence of TARP γ-4 in developing zebrafish. We find that zebrafish express 2 forms of TARP γ-4: γ-4a and γ-4b as early as 12 h post-fertilization. Sequence analysis shows that both γ-4a and γ-4b shows great level of variation particularly in the intracellular C-terminal domain compared to rat, mouse, and human γ-4. RT-qPCR showed a gradual increase in the expression of γ-4a throughout the first 5 days of development, whereas γ-4b levels were constant until day 5 when levels increased significantly. Knockdown of TARP γ-4a and γ-4b via either splice-blocking morpholinos or translation-blocking morpholinos resulted in embryos that exhibited deficits in C-start escape responses, showing reduced C-bend angles. Morphant larvae displayed reduced bouts of swimming. Whole-cell patch-clamp recordings of AMPAR-mediated currents from Mauthner cells showed a reduction in the frequency of mEPCs but no change in amplitude or kinetics. Together, these results suggest that γ-4a and γ-4b are required for proper neuronal development., (© 2022 S. Karger AG, Basel.)

Motivation: Accurate disease phenotype prediction plays an important role in the treatment of heterogeneous diseases like cancer in the era of precision medicine. With the advent of high throughput technologies, more comprehensive multi-omics data is now available that can effectively link the genotype to phenotype. However, the interactive relation of multi-omics datasets makes it particularly challenging to incorporate different biological layers to discover the coherent biological signatures and predict phenotypic outcomes. In this study, we introduce omicsGAN, a generative adversarial network model to integrate two omics data and their interaction network. The model captures information from the interaction network as well as the two omics datasets and fuse them to generate synthetic data with better predictive signals., Results: Large-scale experiments on The Cancer Genome Atlas breast cancer, lung cancer and ovarian cancer datasets validate that (i) the model can effectively integrate two omics data (e.g. mRNA and microRNA expression data) and their interaction network (e.g. microRNA-mRNA interaction network). The synthetic omics data generated by the proposed model has a better performance on cancer outcome classification and patients survival prediction compared to original omics datasets. (ii) The integrity of the interaction network plays a vital role in the generation of synthetic data with higher predictive quality. Using a random interaction network does not allow the framework to learn meaningful information from the omics datasets; therefore, results in synthetic data with weaker predictive signals., Availability and Implementation: Source code is available at: https://github.com/CompbioLabUCF/omicsGAN., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Developing an efficient, concise synthesis of the fungal natural product illudalic acid has been a long-standing challenge, made more pressing by the recent discovery that illudalic acid and analogs are selective phosphatase inhibitors. Syntheses of illudalic acid have become progressively more efficient over the decades yet remain strategically grounded in a 17-step synthesis reported in 1977. Here we validate a two-step process-convergent [4 + 2] benzannulation and one-pot coordinated functional group manipulations-for preparing the key trifunctional pharmacophore of illudalic acid. The modular building blocks are readily available in 2-3 steps, for a longest linear sequence (LLS) of 5 steps to illudalic acid from 3,3-dimethylcyclopentanone. A small collection of analogous indanes and tetralins featuring the same pharmacophore were prepared by a similar route. These compounds potently and selectively inhibit the human leukocyte common antigen-related (LAR) subfamily of protein tyrosine phosphatases (PTPs). Evidence supporting a postulated covalent ligation mechanism is provided herein.

Deregulation of gene expression is associated with the pathogenesis of numerous human diseases including cancer. Current data analyses on gene expression are mostly focused on differential gene/transcript expression in big data-driven studies. However, a poor connection to the proteome changes is a widespread problem in current data analyses. This is partly due to the complexity of gene regulatory pathways at the post-transcriptional level. In this study, we overcome these limitations and introduce a graph-based learning model, PTNet, which simulates the microRNAs (miRNAs) that regulate gene expression post-transcriptionally in silico. Our model does not require large-scale proteomics studies to measure the protein expression and can successfully predict the protein levels by considering the miRNA-mRNA interaction network, the mRNA expression, and the miRNA expression. Large-scale experiments on simulations and real cancer high-throughput datasets using PTNet validated that (i) the miRNA-mediated interaction network affects the abundance of corresponding proteins and (ii) the predicted protein expression has a higher correlation with the proteomics data (ground-truth) than the mRNA expression data. The classification performance also shows that the predicted protein expression has an improved prediction power on cancer outcomes compared to the prediction done by the mRNA expression data only or considering both mRNA and miRNA. Availability: PTNet toolbox is available at http://github.com/CompbioLabUCF/PTNet., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The discovery of CRISPR-Cas9 system has revolutionized the genome engineering research and has been established as a gold standard genome editing platform. This system has found its application in biochemical researches as well as in medical fields including disease diagnosis, development of therapeutics, etc. The enormous versatility of the CRISPR-Cas9 as a high throughput genome engineering platform, is derailed by its off-target activity. To overcome this, researchers from all over the globe have explored the system structurally and functionally and postulated several strategies to upgrade the system components including redesigning of Cas9 Nuclease and modification of guide RNA(gRNA) structure and customization of the protospacer adjacent motif. Here in this review, we portray the comprehensive overview of the strategies that has been adopted for redesigning the CRISPR-Cas9 system to enhance the efficiency and fidelity of the technology., Competing Interests: Conflict of interest The authors declare that there was no conflict of interest., (© 2021 Elsevier Inc. All rights reserved.)

Background: Drug sensitivity prediction and drug responsive biomarker selection on high-throughput genomic data is a critical step in drug discovery. Many computational methods have been developed to serve this purpose including several deep neural network models. However, the modular relations among genomic features have been largely ignored in these methods. To overcome this limitation, the role of the gene co-expression network on drug sensitivity prediction is investigated in this study., Methods: In this paper, we first introduce a network-based method to identify representative features for drug response prediction by using the gene co-expression network. Then, two graph-based neural network models are proposed and both models integrate gene network information directly into neural network for outcome prediction. Next, we present a large-scale comparative study among the proposed network-based methods, canonical prediction algorithms (i.e., Elastic Net, Random Forest, Partial Least Squares Regression, and Support Vector Regression), and deep neural network models for drug sensitivity prediction. All the source code and processed datasets in this study are available at https://github.com/compbiolabucf/drug-sensitivity-prediction ., Results: In the comparison of different feature selection methods and prediction methods on a non-small cell lung cancer (NSCLC) cell line RNA-seq gene expression dataset with 50 different drug treatments, we found that (1) the network-based feature selection method improves the prediction performance compared to Pearson correlation coefficients; (2) Random Forest outperforms all the other canonical prediction algorithms and deep neural network models; (3) the proposed graph-based neural network models show better prediction performance compared to deep neural network model; (4) the prediction performance is drug dependent and it may relate to the drug's mechanism of action., Conclusions: Network-based feature selection method and prediction models improve the performance of the drug response prediction. The relations between the genomic features are more robust and stable compared to the correlation between each individual genomic feature and the drug response in high dimension and low sample size genomic datasets.

Cannabis is one of the most commonly used illicit recreational drugs that is often taken for medicinal purposes. The psychoactive ingredient in cannabis is Δ 9 -Tetrahydrocannabinol (Δ 9 -THC, hereafter referred to as THC), which is an agonist at the endocannabinoid receptors CB 1 R and CB 2 R. Here, we exposed zebrafish embryos to THC during the gastrulation phase to determine the long-term effects during development. We specifically focused on reticulospinal neurons known as the Mauthner cells (M-cell) that are involved in escape response movements. The M- cells are born during gastrulation, thus allowing us to examine neuronal morphology of neurons born during the time of exposure. After the exposure, embryos were allowed to develop normally and were examined at two days post-fertilization for M-cell morphology and escape responses. THC treated embryos exhibited subtle alterations in M-cell axon diameter and small changes in escape response dynamics to touch. Because escape responses were altered, we also examined muscle fiber development. The fluorescent labelling of red and white muscle fibers showed that while muscles were largely intact, the fibers were slightly disorganized with subtle but significant changes in the pattern of expression of nicotinic acetylcholine receptors. However, there were no overt changes in the expression of nicotinic receptor subunit mRNA ascertained by qPCR. Embryos were allowed to further develop until 5 dpf, when they were examined for overall levels of movement. Animals exposed to THC during gastrulation exhibited reduced activity compared with vehicle controls. Together, these findings indicate that zebrafish exposed to THC during the gastrula phase exhibit small changes in neuronal and muscle morphology that may impact behavior and locomotion.

Leukemia is a life-threatening disease. So far diagnosing of leukemia is manually carried out by the Hematologists that is time-consuming and error-prone. The crucial problem is leukocytes' nuclei segmentation precisely. This paper presents a novel technique to solve the problem by applying statistical methods of Gaussian mixture model through expectation maximization for the basic and challenging step of leukocytes' nuclei segmentation. The proposed technique is being tested on a set of 365 images and the segmentation results are validated both qualitatively and quantitatively with current state-of-the-art methods on the basis of ground truth data (manually marked images by medical experts). The proposed technique is qualitatively compared with current state-of-the-art methods on the basis of ground truth data through visual inspection on four different grounds. Finally, the proposed technique quantitatively achieved an overall segmentation accuracy, sensitivity and precision of 92.8%, 93.5% and 98.16% respectively while an overall F-measure of 95.75%.

Malaria is a serious worldwide disease, caused by a bite of a female Anopheles mosquito. The parasite transferred into complex life round in which it is grown and reproduces into the human body. The detection and recognition of Plasmodium species are possible and efficient through a process called staining (Giemsa). The staining process slightly colorizes the red blood cells (RBCs) but highlights Plasmodium parasites, white blood cells and artifacts. Giemsa stains nuclei, chromatin in blue tone and RBCs in pink color. It has been reported in numerous studies that manual microscopy is not a trustworthy screening technique when performed by nonexperts. Malaria parasites host in RBCs when it enters the bloodstream. This paper presents segmentation of Plasmodium parasite from the thin blood smear points on region growing and dynamic convolution based filtering algorithm. After segmentation, malaria parasite classified into four Plasmodium species: Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malaria. The random forest and K-nearest neighbor are used for classification base on local binary pattern and hue saturation value features. The sensitivity for malaria parasitemia (MP) is 96.75% on training and testing of the proposed approach while specificity is 94.59%. Beside these, the comparisons of the two features are added to the proposed work for classification having sensitivity is 83.60% while having specificity is 94.90% through random forest classifier based on local binary pattern feature., (© 2019 Wiley Periodicals, Inc.)

Malaria parasitemia diagnosis and grading is hard and still far from perfection. Inaccurate diagnosis and grading has caused tremendous deaths rate particularly in young children worldwide. The current research deeply reviews automated malaria parasitemia diagnosis and grading in thin blood smear digital images through image analysis and computer vision based techniques. Actually, state-of-the-art reveals that current proposed practices present partially or morphology dependent solutions to the problem of computer vision based microscopy diagnosis of malaria parasitemia. Accordingly, a deep appraisal of the current practices is investigated, compared and analyzed on benchmark datasets. The open gaps are highlighted and the future directions are laid down for a complete automated microscopy diagnosis for malaria parasitemia based on those factors that have not been affected by other diseases. Moreover, a general computer vision framework to perform malaria parasitemia estimation/grading is constructed in universal directions. Finally, remaining problems are highlighted and possible directions are suggested. RESEARCH HIGHLIGHTS: The current research presents a microscopic malaria parasitemia diagnosis and grading of malaria in thin blood smear digital images through image analysis and computer vision based techniques. The open gaps are highlighted and future directions for a complete automated microscopy diagnosis of malaria parasitemia mentioned., (© 2018 Wiley Periodicals, Inc.)

Marijuana is one of the most commonly used illicit recreational drugs and is widely used for medicinal purposes. The psychoactive ingredient in marijuana is ∆ 9 -tetrahydrocannabinol (∆ 9 -THC), whereas the major non-psychoactive ingredient is cannabidiol (CBD). Here, we exposed zebrafish embryos to ∆ 9 -THC or CBD for 5 hours during the critical stage of development known as gastrulation. Embryos were allowed to develop normally and were examined at 2 and 5 days post fertilization. THC and CBD treated embryos exhibited reduced heart rates, axial malformations and shorter trunks. Cannabinoid treatment altered synaptic activity at neuromuscular junctions (NMJs), and fluorescent labelling of primary and secondary motor neurons indicated a change in branching patterns and a reduction in the number of axonal branches in the trunk musculature. Furthermore, there were alterations in the α-bungarotoxin labelling of nicotinic acetylcholine receptors at NMJs. Locomotion studies show that larvae exposed to THC or CBD during gastrulation exhibited drastic reductions in the number of C-start escape responses to sound stimuli, but not to touch stimuli. Together these findings indicate that zebrafish embryos exposed to ∆ 9 -THC or CBD during the brief but critical period of gastrulation exhibited alterations in heart rate, motor neuronal morphology, synaptic activity at the NMJ and locomotor responses to sound.

[Purpose] This study was conducted to evaluate the effect of Inspiratory Muscle Trainer (IMT) on respiratory muscle strength and pulmonary functions. [Subjects and Methods] Fifteen sedentary unemployed patients were recruited from both genders who received regular hemodialysis sessions from at least three months. Those patients received Threshold IMT program for 12 weeks. Pulmonary functions and respiratory muscle strength in form of (PImax) and (PEmax) were measured by electronic spirometry and digital pressure vacuum meter respectively. Additionally oxygen saturation was measured by Finger pulse oximeter. All measurements were performed before and at the end of the treatment program after 12 weeks. [Results] The results of this study revealed significant improvement in FVC%, FEV1%, PEF%, PImax and PEmax after three months of treatment by using inspiratory muscle trainer while no significant difference was recorded regarding to FEV1/FVC% ratio and SpO 2 . [Conclusion] Inspiratory muscle trainer is an effective therapeutic technique to improve respiratory muscle strength and pulmonary functions in patients undergoing hemodialysis.

In this study, we examined the effects of alcohol exposure during gastrulation on zebrafish embryos, specifically focusing on excitatory synaptic activity associated with neurons (Mauthner cells) that are born during gastrulation. Furthermore, we determined whether co-treatment of alcohol and retinoic acid (RA) could prevent the effects of alcohol exposure during gastrulation. We exposed zebrafish embryos to ethanol (150mM), RA (1nM), or a combination of RA (1nM) plus ethanol (150mM) for 5.5h from 5.25h post fertilization (hpf) to 10.75 hpf (gastrulation). Ethanol treatment resulted in altered hatching rates, survivability and body lengths. Immunohistochemical analysis of Mauthner cells (M-cells) suggested that ethanol treatment resulted in smaller M-cell bodies and thinner axons, while electrophysiological recordings of AMPA miniature excitatory postsynaptic currents (mEPSCs) associated with M-cells showed that ethanol treated animals had a significantly reduced mEPSC frequency. Other mEPSC parameters such as amplitude, rise times and decay kinetics were not altered by exposure to alcohol. Locomotor studies showed that ethanol treatment resulted in altered C-bend escape responses. For instance, the C-bends of alcohol-treated fish were larger than control embryos. Thus, ethanol treatment during gastrulation altered a range of features in embryonic zebrafish. Importantly, co-treatment with RA prevented all of the effects of ethanol including survivability, body length, M-cell morphology, AMPA mEPSC frequency and escape response movements. Together these findings show that ethanol exposure during the brief period of gastrulation has a significant effect on neuronal morphology and activity, and that this can be prevented with RA co-treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely., Competing Interests: Conflict-of-interest statement: All the authors have no conflicts of interests to declare.

Context: Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce., Objective: To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects., Materials and Methods: Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field and formalin tests., Results: 2064H was shown to bind to the serotonin 2C (5-HT 2C ) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [ 3 H]-mesulergine with an IC 50 value of 179 ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first minute of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test., Discussion and Conclusion: Overall, manipulating the 5-HT 2C receptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds., Competing Interests: Declaration of Interest The authors report no conflicts of interest.

Nicotinic acetylcholine receptors (nAChRs) are highly expressed at the vertebrate neuromuscular junction (NMJ) where they are required for muscle activation. Understanding the factors that underlie NMJ development is critical for a full understanding of muscle function. In this study we performed whole cell and outside-out patch clamp recordings, and single-cell RT-qPCR from zebrafish red and white muscle to examine the properties of nAChRs during the first 5 days of development. In red fibers miniature endplate currents (mEPCs) exhibit single exponential time courses at 1.5 days postfertilization (dpf) and double exponential time courses from 2 dpf onwards. In white fibers, mEPCs decay relatively slowly, with a single exponential component at 1.5 dpf. By 2 and 3 dpf, mEPC kinetics speed up, and decay with a double exponential component, and by 4 dpf the exponential decay reverts back to a single component. Single channel recordings confirm the presence of two main conductance classes of nAChRs (∼45 pS and ∼65 pS) in red fibers with multiple time courses. Two main conductance classes are also present in white fibers (∼55 pS and ∼73 pS), but they exhibit shorter mean open times by 5 dpf compared with red muscle. RT-qPCR of mRNA for nicotinic receptor subunits supports a switch from γ to ε subunits in white fibers but not in red. Our findings provide a developmental profile of mEPC properties from red and white fibers in embryonic and larval zebrafish, and reveal previously unknown differences between the NMJs of these muscle fibers.© 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 916-936, 2016., (© 2015 Wiley Periodicals, Inc.)

Fast excitatory synaptic transmission in the CNS is mediated by the neurotransmitter glutamate, binding to and activating AMPA receptors (AMPARs). AMPARs are known to interact with auxiliary proteins that modulate their behavior. One such family of proteins is the transmembrane AMPA receptor-related proteins, known as TARPs. Little is known about the role of TARPs during development, or about their function in non-mammalian organisms. Here we report the presence of TARPs, specifically the prototypical TARP, stargazin, in developing zebrafish. We find that zebrafish express two forms of stargazin, Cacng2a and Cacng2b from as early as 12-h post fertilization (hpf). Knockdown of Cacng2a and Cacng2b via splice-blocking morpholinos resulted in embryos that exhibited deficits in C-start escape responses, showing reduced C-bend angles, smaller tail velocities and aberrant C-bend turning directions. Injection of the morphants with Cacng2a or 2b mRNA rescued the morphological phenotype and the synaptic deficits. To investigate the effect of reduced Cacng2a and 2b levels on synaptic physiology, we performed whole cell patch clamp recordings of AMPA mEPSCs from zebrafish Mauthner cells. Knockdown of Cacng2a results in reduced AMPA currents and lower mEPSC frequencies, whereas knockdown of Cacng2b displayed no significant change in mEPSC amplitude or frequency. Non-stationary fluctuation analysis confirmed a reduction in the number of active synaptic receptors in the Cacng2a but not in the Cacng2b morphants. Together, these results suggest that Cacng2a is required for normal trafficking and function of synaptic AMPARs, while Cacng2b is largely non-functional with respect to the development of AMPA synaptic transmission., (© 2015 Wiley Periodicals, Inc.)

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.

Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation. However, if gestation ensued; it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion, prematurity, pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage, and a potential for life-threatening variceal hemorrhage and hepatic decompensation. In contrary, with orthotopic liver transplantation, menstruation resumes and most women of childbearing age are able to conceive, give birth and lead a better quality of life. Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist, maternal-fetal medicine specialist and other specialists. Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection. Furthermore, these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants. Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population. Recent reports suggest that with close monitoring and multidisciplinary team approach, most female liver transplant recipient of childbearing age will lead a successful pregnancy.

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. This review summarizes liver diseases that are unique to pregnancy. We discuss clinical conditions that are seen only in pregnant women and involve the liver; from Hyperemesis Gravidarum that happens in 1 out of 200 pregnancies and Intrahepatic Cholestasis of Pregnancy (0.5%-1.5% prevalence), to the more frequent condition of preeclampsia (10% prevalence) and its severe form; hemolysis, elevated liver enzymes, and a low platelet count syndrome (12% of pregnancies with preeclampsia), to the rare entity of Acute Fatty Liver of Pregnancy (incidence of 1 per 7270 to 13000 deliveries). Although pathogeneses behind the development of these aliments are not fully understood, theories have been proposed. Some propose the special physiological changes that accompany pregnancy as a precipitant. Others suggest a constellation of factors including both the mother and her fetus that come together to trigger those unique conditions. Reaching a timely and accurate diagnosis of such conditions can be challenging. The timing of the condition in relation toward which trimester it starts at is a key. Accurate diagnosis can be made using specific clinical findings and blood tests. Some entities have well-defined criteria that help not only in making the diagnosis, but also in classifying the disease according to its severity. Management of these conditions range from simple medical remedies to measures such as immediate termination of the pregnancy. In specific conditions, it is prudent to have expert obstetric and medical specialists teaming up to help improve the outcomes.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis. This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia, and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes, and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing. Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome, both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.

Human amniotic membrane is considered a promising allograft material for the treatment of ocular surface reconstruction, burns, and other skin defects. In order to avoid the transmission of any diseases, grafts should be perfectly sterile. Twenty-five amniotic sacs were collected to determine the microbiological quality of human amniotic membrane, to analyze the radiation sensitivity pattern of the microorganism, and to detect the radiation decimal reduction dose (D₁₀) values. All the samples were found to be contaminated, and the bioburden was ranged from 3.4 × 10² to 1.2 × 10⁵ cfu/g. Initially, a total fifty bacterial isolates were characterized according to their cultural, morphological, and biochemical characteristics and then tested for the radiation sensitivity in an incremental series of radiation doses from 1 to 10 KGy. The results depict gradual decline in bioburden with incline of radiation doses. Staphylococcus spp. were the most frequently isolated bacterial contaminant in tissue samples (44%). The D₁₀ values of the bacterial isolates were ranged from 0.6 to 1.27 KGy. Streptococcus spp. were found to be the highest radioresistant strain with the radiation sterilization dose (RSD) of 11.4 KGy for a bioburden level of 1000. To compare the differences, D₁₀ values were also calculated by graphical evaluations of the data with two of the representative isolates of each bacterial species which showed no significant variations. Findings of this study indicate that lower radiation dose is quite satisfactory for the sterilization of amniotic membrane grafts. Therefore, these findings would be helpful to predict the efficacy of radiation doses for the processing of amniotic membrane for various purposes.

The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5) and 360 controls (BMI 18.5-24.99) were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant's age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment of coronary artery disease. Its mechanism of action remains unknown. An acute coronary occlusion dog model was created to explore the angiogenic effect of EECP. After coronary occlusion, 12 dogs were randomly assigned to either EECP (n = 6) or control (n = 6). Immunohistochemical studies of alpha-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by ELISA and reverse transcriptase PCR analysis. There was a significant increase in the density of microvessels per squared millimeter in the infarcted regions of the EECP group compared with the control group (vWF, 15.2 +/- 6.3 vs. 4.9 +/- 2.1, P < 0.05; alpha-actin, 11.8 +/- 5.3 vs. 3.4 +/- 1.2, P < 0.05). The positive-stained area per squared micrometer also increased significantly (alpha-actin, 6.6 x 10(3) +/- 2.9 x 10(3) microm2 vs. 0.6 x 10(3) +/- 0.5 x 10(3) microm2, P < 0.05; vWF, 5.7 x 10(3) +/- 1.9 x 10(3) microm2 vs. 1.7 x 10(3) +/- 1.4 x 10(3) microm2, P < 0.05). Immunohistochemical staining and reverse transcriptase PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography. Angiogenesis may be a mechanism of action for the improved myocardial perfusion demonstrated after EECP therapy.