Clinical presentation of post-COVID pain and its impact on quality of life in long COVID patients: a cross-sectional household survey of SARS-CoV-2 cases in Bangladesh.

BACKGROUND: Pain is one of the prevalent Long COVID Symptoms (LCS). Pain interferes with the quality of life (QoL) and induces disease burden. PURPOSE: The study aimed to elicit the clinical presentation of pain and determine the relationships between QoL and pain in LCS. METHODS: This household cross-sectional study of 12,925 SARS-CoV-2 cases between July and December 2021 was carried out in eight administrative divisions of Bangladesh. Stratified random sampling from the cases retrieved from the Ministry of Health was employed. Symptom screening was performed through COVID-19 Yorkshire Rehabilitation Scale, and long COVID was diagnosed according to World Health Organization (WHO) criteria. The analyses were conducted using IBM SPSS (Version 20.00). RESULTS: The prevalence of pain in long COVID was between 01 and 3.1% in the studied population. The study also found five categories of pain symptoms as LCS in Bangladesh: muscle pain 3.1% (95% CI; 2.4-3.8), chest pain 2.4% (95% CI; 1.8-3.1), joint pain 2.8% (95% CI; 2.2-2.3), headache 3.1% (95% CI; 2.4-3.8), and abdominal pain 0.3% (95% CI; 0.01-0.5). People with LCS as pain, multiple LCS, and longer duration of LCS had significantly lower quality of life across all domains of the WHOQOL-BREF (P < 0.001) compared to asymptomatic cases. CONCLUSION: Three out of ten people with long COVID experience painful symptoms, which can significantly reduce their quality of life. Comprehensive rehabilitation can improve the symptoms and reduce the burden of the disease.

Availability and readiness of healthcare facilities and their effects on antenatal care services uptake in Bangladesh.

BACKGROUND: Sustainable Development Goal (SDG) 3.7 aims to ensure universal access to sexual and reproductive healthcare services, where antenatal care (ANC) is a core component. This study aimed to examine the influence of health facility availability and readiness on the uptake of four or more ANC visits in Bangladesh. METHODS: The 2017/18 Bangladesh Demographic and Health Survey data were linked with the 2017 Health Facility Survey and analyzed in this study. The associations of health facility-level factors with the recommended number of ANC uptakes were determined. A multilevel mixed-effect logistic regression model was used to determine the association, adjusting for potential confounders. RESULTS: Nearly 44% of mothers reported four or more ANC uptakes, with significant variations across several areas in Bangladesh. The average distance of mothers' homes from the nearest health facilities was 6.36 km, higher in Sylhet division (8.25 km) and lower in Dhaka division (4.45 km). The overall uptake of the recommended number of ANC visits was positively associated with higher scores for the management (adjusted odds ratio (aOR) 1.85; 95% CI, 1.16-2.82) and infrastructure (aOR, 1.59; 95% CI, 1.09-2.19) of health facilities closest to mothers' homes. The odds of using the recommended number of ANC in mothers increased by 3.02 (95% CI, 2.01-4.19) and 2.36 (95% CI, 2.09-3.16) folds for each unit increase in the availability and readiness scores to provide ANC services at the closest health facilities, respectively. Every kilometer increase in the average regional-level distance between mothers' homes and the nearest health facilities reduced the likelihood of receiving the recommended number of ANC visits by nearly 42% (aOR, 0.58, 95% CI, 0.42-0.74). CONCLUSION: The availability of healthcare facilities close to residence, as well as their improved management, infrastructure, and readiness to provide ANC, plays a crucial role in increasing ANC services uptake. Policies and programs should prioritize increasing the availability, accessibility, and readiness of health facilities to provide ANC services.

Chemically induced degradation of epigenetic targets.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules that induce the ternary complex formation between a protein-of-interest (POI) and an E3 ligase, leading to targeted polyubiquitination and degradation of the POI. Particularly, PROTACs have the distinct advantage of targeting both canonical and noncanonical functions of epigenetic targets over traditional inhibitors, which typically target canonical functions only, resulting in greater therapeutic efficacy. In this review, we methodically analyze published PROTAC degraders of epigenetic writer, reader, and eraser proteins and their in vitro and in vivo effects. We highlight the mechanism of action of these degraders and their advantages in targeting both canonical and noncanonical functions of epigenetic targets in the context of cancer treatment. Furthermore, we present a future outlook for this exciting field. Overall, pharmacological degradation of epigenetic targets has emerged as an effective and attractive strategy to thwart cancer progression and growth.

Sustaining rice productivity through weather-resilient agricultural practices.

BACKGROUND: Enhancing productivity and profitability and reducing climatic risk are the major challenges for sustaining rice production. Extreme weather can have significant and varied effects on crops, influencing agricultural productivity, crop yields and food security. RESULTS: In this study, a comparative evaluation of two crop management systems was performed involving farmers adopting a weather forecast-based advisory service (WFBAS) and usual farmers' practice (FP). WFBAS crop management followed the generated weather forecast-based advice whereas the control farmers (FP) did not receive any weather forecast-based advice, rather following their usual rice cultivation practices. The results of the experiments revealed that WFBAS farmers had a significant yield advantage over FP farmers. With the WFBAS technology, the farmers used inputs judiciously, utilized the benefit of favorable weather and minimized the risk resulting from extreme weather events. As a result, besides the yield enhancement, WFBAS provided a scope to protect the environment with the minimum residual effect of fertilizer and pesticides. It also reduced the pressure on groundwater by ensuring efficient water management. Finally, the farmers benefited from higher income through yield enhancement, reduction of the costs of production and reduction of risk. CONCLUSION: A successful and extensive implementation of WFBAS in the rice production system would assist Bangladesh in achieving Sustainable Development Goal 2.4, which focuses on rice productivity and profitability of farmers as well as long-term food security of the country. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Acetylation Targeting Chimera Enables Acetylation of the Tumor Suppressor p53.

With advances in chemically induced proximity technologies, heterobifunctional modalities such as proteolysis targeting chimeras (PROTACs) have been successfully advanced to clinics for treating cancer. However, pharmacologic activation of tumor-suppressor proteins for cancer treatment remains a major challenge. Here, we present a novel Acetylation Targeting Chimera (AceTAC) strategy to acetylate the p53 tumor suppressor protein. We discovered and characterized the first p53Y220C AceTAC, MS78, which recruits histone acetyltransferase p300/CBP to acetylate the p53Y220C mutant. MS78 effectively acetylated p53Y220C lysine 382 (K382) in a concentration-, time-, and p300-dependent manner and suppressed proliferation and clonogenicity of cancer cells harboring the p53Y220C mutation with little toxicity in cancer cells with wild-type p53. RNA-seq studies revealed novel p53Y220C-dependent upregulation of TRAIL apoptotic genes and downregulation of DNA damage response pathways upon acetylation induced by MS78. Altogether, the AceTAC strategy could provide a generalizable platform for targeting proteins, such as tumor suppressors, via acetylation.

Method to fabricate round cross-sectional channel using thermal expansion of air for passive flow regulators.

We present a novel method for fabricating round cross-sectional channels for autoregulatory pressure regulators. The application of previously reported methods in multilayered soft lithography using three-dimensional printed molds is challenging. Herein, we used a thermal expansion technique to create round cross-sectional channels in replica layers using air in the cavity space of a master mold. The width and height of the round channel in the replica could be adjusted in the range of 80-300 and 3-57 µm, respectively, by varying the precuring time of the replica in the gel state and adjusting the cavity size of the master mold. We successfully fabricated a pressure regulator with a round cross-sectional channel, achieving a constant output pressure at a low threshold input pressure. Our device exhibited superior performance, with a constant output pressure at a threshold input pressure of less than 77%, compared to a device with a rectangular cross-sectional channel. Our method has significant potential for application in the fabrication of integrated microfluidic systems with round cross-sectional channels.

50 years of rice breeding in Bangladesh: genetic yield trends.

To assess the efficiency of genetic improvement programs, it is essential to assess the genetic trend in long-term data. The present study estimates the genetic trends for grain yield of rice varieties released between 1970 and 2020 by the Bangladesh Rice Research Institute. The yield of the varieties was assessed from 2001-2002 to 2020-2021 in multi-locations trials. In such a series of trials, yield may increase over time due to (i) genetic improvement (genetic trend) and (ii) improved management or favorable climate change (agronomic/non-genetic trend). In both the winter and monsoon seasons, we observed positive genetic and non-genetic trends. The annual genetic trend for grain yield in both winter and monsoon rice varieties was 0.01 t ha-1, while the non-genetic trend for both seasons was 0.02 t ha-1, corresponding to yearly genetic gains of 0.28% and 0.18% in winter and monsoon seasons, respectively. The overall percentage yield change from 1970 until 2020 for winter rice was 40.96%, of which 13.91% was genetic trend and 27.05% was non-genetic. For the monsoon season, the overall percentage change from 1973 until 2020 was 38.39%, of which genetic and non-genetic increases were 8.36% and 30.03%, respectively. Overall, the contribution of non-genetic trend is larger than genetic trend both for winter and monsoon seasons. These results suggest that limited progress has been made in improving yield in Bangladeshi rice breeding programs over the last 50 years. Breeding programs need to be modernized to deliver sufficient genetic gains in the future to sustain Bangladeshi food security.

Predictive Models for Human Cytochrome P450 3A7 Selective Inhibitors and Substrates.

Inappropriate use of prescription drugs is potentially more harmful in fetuses/neonates than in adults. Cytochrome P450 (CYP) 3A subfamily undergoes developmental changes in expression, such as a transition from CYP3A7 to CYP3A4 shortly after birth, which provides a potential way to distinguish medication effects on fetuses/neonates and adults. The purpose of this study was to build first-in-class predictive models for both inhibitors and substrates of CYP3A7/CYP3A4 using chemical structure analysis. Three metrics were used to evaluate model performance: area under the receiver operating characteristic curve (AUC-ROC), balanced accuracy (BA), and Matthews correlation coefficient (MCC). The performance varied for each CYP3A7/CYP3A4 inhibitor/substrate model depending on the data set type, model type, rebalancing method, and specific feature set. For the active inhibitor/substrate data set, the optimal models achieved AUC-ROC values ranging from 0.77 ± 0.01 to 0.84 ± 0.01. For the selective inhibitor/substrate data set, the optimal models achieved AUC-ROC values ranging from 0.72 ± 0.02 to 0.79 ± 0.04. The predictive power of the optimal models was validated by compounds with known potencies as CYP3A7/CYP3A4 inhibitors or substrates. In addition, we identified structural features significant for CYP3A7/CYP3A4 selective or common inhibitors and substrates. In summary, the top performing models can be further applied as a tool to rapidly evaluate the safety and efficacy of new drugs separately for fetuses/neonates and adults. The significant structural features could guide the design of new therapeutic drugs as well as aid in the optimization of existing medicine for fetuses/neonates.

Status of lipid control in Bangladeshi subjects with type 2 diabetes mellitus on lipid-lowering drugs: a multicenter, facility-based, cross-sectional study.

BACKGROUND: Achievement of lipid targets is crucial in patients with type 2 diabetes mellitus (T2DM) to mitigate the risk of cardiovascular diseases (CVD). Data on lipid-control status among patients with T2DM in Bangladesh are scarce. This study was conducted to determine the lipid-control status among patients with T2DM who were on lipid-lowering drugs in the country. METHODS: This cross-sectional study was conducted in the diabetes outpatient departments of several tertiary hospitals in Bangladesh from January 2022 to December 2022. Adults of both sexes diagnosed with T2DM for at least one year and were on the lipid-lowering drug(s) for a minimum of 3 months were included in the study by consecutive sampling. Patients' data were collected by face-to-face interviews, and blood samples were collected for fasting lipid profile. The lipid target was set at < 200 mg/dL for total cholesterol (TC), < 150 mg/dL for triglyceride (TG), < 100 mg/dL for low-density lipoprotein cholesterol (LDL-C), > 40 mg/dL for high-density lipoprotein cholesterol (HDL-C), and < 160 mg/dL for non-HDL cholesterol (non-HDL-C). RESULT: Three thousand sixty patients (age 44.7 ± 13.3 years, female 57%) with T2DM were evaluated. Overall, almost 81% of the study subjects achieved the LDL-C target. Besides, TC, TG, HDL-C, and non-HDL-C targets were achieved by 40.8, 21.6, 66.3, and 44.1% of patients, respectively. However, all the lipid parameters were under control in only 8.8% of patients. Almost 77.6% of the patients with ischemic heart disease, 81.5% of patients with stroke, and 65% of patients with CKD had LDL levels < 70 mg/dL. Only 10.03% achieved the HbA1c target of < 7%. 7.4% of patients achieved both HbA1c < 7% and LDL < 100 mg/dL and 5% achieved both HbA1c < 7% and LDL < 70 mg/dL. Advanced age (aOR 0.97, 95% CI 0.96, 0.98, p < 0.001), longstanding T2DM (aOR 0.53, 95% CI 0.39, 0.72, p < 0.001), and non-statin therapy (aOR 0.25, 95% CI 0.16, 0.37, p < 0.001) were negatively associated with lipid control (LDL < 100 mg/dL) while using oral hypoglycemic drugs or insulin (aOR 2.01, 95% CI 1.45, 2.77, p < 0.001) and having cardiovascular comorbidity (aOR 3.92, 95% CI 3.00, 5.12, p < 0.001) were positively associated with lipid control. CONCLUSION: Though most patients with T2DM achieved their target LDL level, the prevalence of both glycemic and overall lipid control was low in our study despite lipid-lowering therapy.

Comparison of simplicity, convenience, safety, and cost-effectiveness between use of insulin pen devices and disposable plastic syringes by patients with type 2 diabetes mellitus: a cross-sectional study from Bangladesh.

INTRODUCTION: Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers; higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. RESULTS: 737 subjects were evaluated; 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity [6.0 (5.0-8.0) vs. 7.0 (5.0-9.0), p = 0.002], convenience [4.0 (3.0-6.0) vs. 5.0 (4.0-6.0), p < 0.001], and safety [7.0 (6.0-8.0) vs. 7.0 (6.0-9.0), p = 0.008] than vial syringe users. Pen devices were more expensive than vial syringes in terms of average medical expense per month [BDT 5000 (3500-7000) vs. 3000 (2000-5000), p < 0.001], the total cost of insulin therapy per month [BDT 2000 (1500-3000) vs. 1200 (800-1700), p < 0.001] and cost per unit of insulin used [BDT 2.08 (1.39-2.78) vs. 0.96 (0.64-1.39), p < 0.001]. Non-significant differences in favor of pens were observed in HbA1c levels [8.7 (7.8-10) vs. 8.9 (7.9-10)%, p = 0.607] and proportions of subjects having HbA1c < 7% (6.9 vs. 6.3%, p = 0.991). CONCLUSION: Insulin pens are simpler, more convenient, and safe but more expensive than vial syringes. Glycemic control is comparable between pen and syringe users. Long-term follow-up studies are needed to determine the clinical and economic impacts of such benefits of insulin pens.

Genetic variability of Haemonchus contortus isolates in small ruminants from slaughterhouses in Bangladesh.

Haemonchus contortus is a blood-sucking gastrointestinal nematode that infects all ruminants and causes significant economic losses in production. Characterizing the genetic variability of H. contortus populations is crucial for understanding patterns of disease transmission and developing effective control strategies against haemonchosis. This study aimed to identify the genetic variability of H. contortus isolates in small ruminants from slaughterhouses in Bangladesh. During January to December 2015, 400 abomasa samples were collected and 186 were found to be positive for Haemonchus. A 321-bp fragment of the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA and an 800-bp fragment of the mitochondrial nicotinamide dehydrogenase subunit-4 gene (nad4) were amplified using polymerase chain reaction (PCR) and directly sequenced. The results showed 10 genotypes (ITS-2) and 45 haplotypes (nad4) among the 186 worms. The sequences were 98.5 to 100% identical to reference sequences from the GenBank database. ITS-2 sequence analysis revealed four nucleotide substitutions at positions 30, 41, 42, and 216. There was one transition (C/T) at position 42 and three transversions (C/A at position 30, G/C at position 41, and T/A at position 216). The nad4 gene sequences showed 15 substitutions, all of which were transitions. The pairwise distance of ITS-2 between H. contortus populations ranged from 0.005 to 1.477. The nucleotide diversity (µ) among the populations was 0.009524 using ITS-2 and 0.00394 using nad4. This study indicated low genetic deviation among H. contortus populations in Bangladesh.

Vibration and Slope Conditions during Harvesting Affect Radish Mass Measurements for Yield Monitoring: An Experimental Study Using a Laboratory Test Bench.

Site-specific measurements of the crop yield during harvesting are essential for successfully implementing precision management techniques. This study aimed to estimate the mass of radish tubers using the impact principle under simulated vibration and sloped-field harvesting conditions with a laboratory test bench. These conditions included the conveyor speed (CS), impact plate layout (IP), falling height onto the impact plate (FH), the plate angle relative to the horizontal (PH), the field slope, and the vibration of the harvesting machine. Two layouts of impact-type sensors were fabricated and tested, one with a single load cell (SL) and the other with two load cells (DL). An adjustable slope platform and a vibration table equipped with vibration blades were utilized to simulate the slope and vibration effects, respectively. Calibrations were conducted to verify the accuracy of the sensor outputs, processed with the finite impulse response and moving average filters. Radish mass was estimated using an asymmetrically trimmed mean method. The relative percentage error (RE), standard error (SE), coefficient of determination (R²), and analysis of variance (ANOVA) were used to assess the impact plate performance. The results indicated that the SE for both impact plates was less than 4 g in the absence of vibration and slope conditions. The R2 for the single and double impact plates ranged from 0.58 to 0.89 and 0.69 to 0.81, respectively. The FH had no significant impact, while the PH significantly affected the mass measurements for both impact plates. On the other hand, the CS significantly affected the plate performance, except for the double-load-cell impact plate. Both vibration and slope affected the mass measurements, with RE values of 9.89% and 13.92%, respectively. The RE for filtered radish signals was reduced from 9.13% to 5.42%. The tests demonstrated the feasibility of utilizing the impact principle to assess the mass of radishes, opening up possibilities for the development of yield-monitoring systems for crops harvested in a similar manner.

Deep Learning-Based IoT System for Remote Monitoring and Early Detection of Health Issues in Real-Time.

With an aging population and increased chronic diseases, remote health monitoring has become critical to improving patient care and reducing healthcare costs. The Internet of Things (IoT) has recently drawn much interest as a potential remote health monitoring remedy. IoT-based systems can gather and analyze a wide range of physiological data, including blood oxygen levels, heart rates, body temperatures, and ECG signals, and then provide real-time feedback to medical professionals so they may take appropriate action. This paper proposes an IoT-based system for remote monitoring and early detection of health problems in home clinical settings. The system comprises three sensor types: MAX30100 for measuring blood oxygen level and heart rate; AD8232 ECG sensor module for ECG signal data; and MLX90614 non-contact infrared sensor for body temperature. The collected data is transmitted to a server using the MQTT protocol. A pre-trained deep learning model based on a convolutional neural network with an attention layer is used on the server to classify potential diseases. The system can detect five different categories of heartbeats: Normal Beat, Supraventricular premature beat, Premature ventricular contraction, Fusion of ventricular, and Unclassifiable beat from ECG sensor data and fever or non-fever from body temperature. Furthermore, the system provides a report on the patient's heart rate and oxygen level, indicating whether they are within normal ranges or not. The system automatically connects the user to the nearest doctor for further diagnosis if any critical abnormalities are detected.

Molecular Mapping to Discover Reliable Salinity-Resilient QTLs from the Novel Landrace Akundi in Two Bi-Parental Populations Using SNP-Based Genome-Wide Analysis in Rice.

Achieving high-yield potential is always the ultimate objective of any breeding program. However, various abiotic stresses such as salinity, drought, cold, flood, and heat hampered rice productivity tremendously. Salinity is one of the most important abiotic stresses that adversely affect rice grain yield. The present investigation was undertaken to dissect new genetic loci, which are responsible for salt tolerance at the early seedling stage in rice. A bi-parental mapping population (F2:3) was developed from the cross between BRRI dhan28/Akundi, where BRRI dhan28 (BR28) is a salt-sensitive irrigated (boro) rice mega variety and Akundi is a highly salinity-tolerant Bangladeshi origin indica rice landrace that is utilized as a donor parent. We report reliable and stable QTLs for salt tolerance from a common donor (Akundi) irrespective of two different genetic backgrounds (BRRI dhan49/Akundi and BRRI dhan28/Akundi). A robust 1k-Rice Custom Amplicon (1k-RiCA) SNP marker genotyping platform was used for genome-wide analysis of this bi-parental population. After eliminating markers with high segregation distortion, 886 polymorphic SNPs built a genetic linkage map covering 1526.5 cM of whole rice genome with an average SNP density of 1.72 cM for the 12 genetic linkage groups. A total of 12 QTLs for nine different salt tolerance-related traits were identified using QGene and inclusive composite interval mapping of additive and dominant QTL (ICIM-ADD) under salt stress on seven different chromosomes. All of these 12 new QTLs were found to be unique, as no other map from the previous study has reported these QTLs in the similar chromosomal location and found them different from extensively studied Saltol, SKC1, OsSalT, and salT locus. Twenty-eight significant digenic/epistatic interactions were identified between chromosomal regions linked to or unlinked to QTLs. Akundi acts like a new alternate donor source of salt tolerance except for other usually known donors such as Nona Bokra, Pokkali, Capsule, and Hasawi used in salt tolerance genetic analysis and breeding programs worldwide, including Bangladesh. Integration of the seven novel, reliable, stable, and background independent salinity-resilient QTLs (qSES1, qSL1, qRL1, qSUR1, qSL8, qK8, qK1) reported in this investigation will expedite the cultivar development that is highly tolerant to salt stress.

Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis.

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non-fermented RB were fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

Selection of healthy sperm based on positive rheotaxis using a microfluidic device.

For conception, sperm cells travel towards the oocyte. This journey is accomplished by only a few sperm cells, following various guidance mechanisms. Of these mechanisms, rheotaxis plays a significant role in guiding the sperm over a long distance. By taking advantage of this natural rheotaxis behavior of sperm, we have developed a microfluidic chip that isolates healthy sperm cells. The developed chip consists of different chambers separated by microchannels that facilitate separation of motile sperm cells from unprocessed semen samples with the help of fluid flow. The sperm cells are subjected to different velocities in different parts of the chip that direct functional sperm towards the collection chamber utilizing positive rheotaxis. The results from the developed microfluidic chip (with 0.5 µL min-1 flow rate) have shown almost 100% motility, a significantly higher percentage of morphologically normal sperm cells with lesser sperm DNA fragmentation than the control (no-flow) and raw semen sample. This chip satisfies the need of a clinical setting as it is low-cost, easy to operate and uses a small semen volume for sperm sorting.

Using in vitro ADME data for lead compound selection: An emphasis on PAMPA pH 5 permeability and oral bioavailability.

Membrane permeability plays an important role in oral drug absorption. Caco-2 and Madin-Darby Canine Kidney (MDCK) cell culture systems have been widely used for assessing intestinal permeability. Since most drugs are absorbed passively, Parallel Artificial Membrane Permeability Assay (PAMPA) has gained popularity as a low-cost and high-throughput method in early drug discovery when compared to high-cost, labor intensive cell-based assays. At the National Center for Advancing Translational Sciences (NCATS), PAMPA pH 5 is employed as one of the Tier I absorption, distribution, metabolism, and elimination (ADME) assays. In this study, we have developed a quantitative structure activity relationship (QSAR) model using our ∼6500 compound PAMPA pH 5 permeability dataset. Along with ensemble decision tree-based methods such as Random Forest and eXtreme Gradient Boosting, we employed deep neural network and a graph convolutional neural network to model PAMPA pH 5 permeability. The classification models trained on a balanced training set provided accuracies ranging from 71% to 78% on the external set. Of the four classifiers, the graph convolutional neural network that directly operates on molecular graphs offered the best classification performance. Additionally, an ∼85% correlation was obtained between PAMPA pH 5 permeability and in vivo oral bioavailability in mice and rats. These results suggest that data from this assay (experimental or predicted) can be used to rank-order compounds for preclinical in vivo testing with a high degree of confidence, reducing cost and attrition as well as accelerating the drug discovery process. Additionally, experimental data for 486 compounds (PubChem AID: 1645871) and the best models have been made publicly available (https://opendata.ncats.nih.gov/adme/).

Microglia in Alzheimer's Disease: A Favorable Cellular Target to Ameliorate Alzheimer's Pathogenesis.

Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid ß phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis.

Associations between inappropriate medication use and (instrumental) activities of daily living in geriatric rehabilitation inpatients: RESORT study.

BACKGROUND: Inappropriate medication use can affect functional independence in older adults. AIMS: The aim of the study is to examine associations between potentially inappropriate medication use and Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) in geriatric rehabilitation inpatients. METHODS: A longitudinal, prospective, observational study was undertaken at a teaching hospital. Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were measured at acute admission, and at admission and discharge from geriatric rehabilitation. Associations between PIM and PPO use and ADL and IADL scores were examined at admission to geriatric rehabilitation, discharge and 3-month post-discharge. RESULTS: A total of 693 inpatients were included. At the 3-month post-discharge, PPOs were associated with lower IADL scores (incident rate ratio = 0.868, 95% CI 0.776-0.972). There were no significant associations between PIMs and PPOs use at admission to geriatric rehabilitation with longitudinal changes of ADLs and IADLs from geriatric rehabilitation admission to 3-month post-discharge Renal PIMs were associated with higher IADL scores at 3-month post-discharge (incidence rate ratio = 1.750, 95% CI 1.238-2.474). At 3-month post-discharge, PPOs involving vaccinations were associated with a lower IADL score (incident risk ratio = 0.844, 95% CI 0.754-0.944). CONCLUSIONS: Inappropriate medication use involving PPOs was associated with lower IADL scores at 3-month post-discharge from geriatric rehabilitation but not with ADL scores. Greater attention is needed in reducing PPOs in geriatric rehabilitation inpatients that can potentially impact IADLs. In the community, health professionals need to be vigilant about assessing how older patients' physical functioning may be affected by inappropriate medication prescribing.

Trace element speciation in sludge: a preliminary study to assess contamination levels in the sewage network.

The spreading of sewage sludge from wastewater treatment plants and various industries arouses the growing interest due to the contamination by trace elements. Sludges were collected from one sewage treatment plant and two industries in Dhaka City, Bangladesh to assess physicochemical parameters and total and fraction content of trace elements like Cr, Ni, Cu, As, Cd, Pb, Fe, Mn and Zn in sludges. We evaluated the bioavailability of theses metals by determining their speciation by sequential extraction, each metal being distributed among five fractions: exchangeable fraction, bound to carbonate fraction, Fe-Mn oxide bound fraction, organic matter bound fraction and residual fractions. We found that all the analyzed sludges had satisfactory properties from an agronomic quality point of view. The average concentration (mg/kg) of trace metals in sludge samples were in the following decreasing order Fe (12807) > Cr (200) > Mn (158) > Zn (132) > Cu (68.2) > Ni (42.5) > Pb (36.4) > As (35.1) > Cd (3.7). The results of the sequential extraction showed that Cr, Ni, Cu, Fe and Mn were largely associated with the residual fraction where As, Cd and Pb was dominantly associated with the exchangeable and carbonate bound fractions and Zn showed a considerable proportion in carbonate bound fraction. These results showed that regulations must take into account the bioavailability with regard to the characteristics of the agricultural soils on which sludge will be spread.