Serum creatinine phosphokinase: A potential prognostic marker in assessing clinical severity with organophosphorus poisoning.

INTRODUCTION: Organophosphorus compound (OPC) poisoning undoubtedly being a major concern in cultivation sites of the developing world, including Bangladesh. Two potential biomarkers, for example, serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), are widely used in OPC poisoning severity indicators in patients. In this study, we sought to correlate the severity score of acute OPC poisoning with CPK or LDH level and subsequently explore their prognostic value. METHODS: This study was performed on a total of 70 patients with OPC poisoning admitted to the inpatient care unit at a territory-based hospital in Bangladesh. Sociodemographics and poison types were recorded, and severity was assessed according to Peradeniya Organophosphorus Poisoning (POP) scale. Serum CPK and LDH levels were measured and recorded. RESULTS: A total of seventy OPC patients were included with male to female ratio of 1.33:1, respectively, with a mean age of 28.7 ± 12.8 years. Chlorpyrifos and methylparathion were the most commonly utilized OP compounds, accounting for 42.9% and 28.6%, respectively. Among the OPC patients, the majority were married homemakers from rural areas. According to POP score, 55.7% and 37.1% of patients were categorized as mild and moderate, whereas very few were found to be severe. The mean serum CPK and LDH of OPC-patients at admission time were 235.6 ± 79.8 IU/L and 348.3 ± 154.1 IU/L, respectively. Serum CPK, atropine dose and hospital stay strongly correlated with clinical severity. CONCLUSION: We conclude that the serum CPK level strongly correlates with the degree of OPC poisoning and can be used as a predictor of the clinical intervention approaches.

Isolation of multidrug resistance bacteria from the patients with wound infection and their antibiotics susceptibility patterns: A cross-sectional study.

Introduction: Antimicrobial resistance has become one of the most severe public problems in both developed and developing countries like Bangladesh. In this study, several multi-drug resistant bacteria were isolated from the wound infections and demonstrated their antibiotic susceptibility pattern in Bangladeshi patients. Methods: A total of 699 bacterial isolates were collected from wound swabs and each isolate was identified using gram staining, biochemical assays, antibiotic susceptibility tests with the disk diffusion method, and colony morphology. Samples were taken from January 2018 to December 2019. The analysis was conducted using SPSS (Inc., Chicago, IL, USA), and descriptive statistics were employed to illustrate the findings. Results: We have found 14.4% gram-positive bacteria (n = 100) and 85.6% gram-negative bacteria (n = 595) among the 695 samples by gram staining methods. The most prevalent gram-positive and gram-negative bacteria present in wound infections were Staphylococcus spp. (81.5%) and Pseudomonas spp. (89%), respectively. Antimicrobials that were mostly resistant to gram-negative isolates were Amoxicillin (75.8%), Cefixime (75.5%), Cefuroxime (70.3%), and Ceftazidime (69.6%). On the other hand, cefixime and ceftazidime accounted for 73% of the resistance against gram-positive isolates, followed by amoxicillin (71%), and penicillin-G (69%). Meropenem was found to be the most sensitive antibiotic for gram-negative bacteria. Meropenem and Gentamycin were found to have a percentage of sensitivity for gram-positive bacteria. Based on the assessment of 13 different antimicrobial classes, the percentage of multi-drug resistant bacteria identified in gram-negative bacteria was 84% and in gram-positive bacteria was 79%. Among gram-negative bacterial isolates, 82% pseudomonas spp, 88.5% Klebsiella spp, and 91.6% Proteus spp were reported as multi-drug resistant. On the other hand, Pseudomonas spp, Klebsiella spp, and Proteus spp. were found to be multi-drug resistant in 82%, 88.5%, and 91.6% of gram-negative bacterial isolates, respectively. It was shown that staphylococcus aureus (81%) and staphylococcus spp (78.6%) became gram-positive among gram-positive isolates. Conclusion: According to this study, frequently isolated bacteria have a high frequency of MDR, which is the most pressing issue in public health. This study helps to manage the evidence-based treatment strategy and the urgency of early identification of drug-resistant bacteria that can reduce disease burden.

RLLB/Alb ratio: a promising noninvasive diagnostic marker in assessing esophageal varices in cirrhotic patients.

BACKGROUND: Endoscopy has long been widely used to screen for esophageal varices (EV) in cirrhotic patients. Recurrent endoscopy is a significant burden for the healthcare system of the endoscopic unit as well as uncomfortable and high costs for patients. This study intended to prognosticate Right Liver Lobe Diameter/Serum Albumin Ratio (RLLD/Alb) as a non-invasive approach in the early diagnosis of EV among chronic liver disease (CLD) Bangladeshi patients enrolled in a specific hospital. PARTICIPANTS AND METHODS: A total of 150 admitted patients with CLD were included in the study. Patients were subjected through a comprehensive biochemical checkup and upper digestive endoscopic or ultrasonographic inspection. The correlation was evaluated between the RLLD/Alb ratio and esophageal varices grades. RESULTS: The upper digestive endoscopy demonstration among 150 patients resulted in no EV in 18%, while 24% of patients was identified as EV grade I, 20% as grade II, 20% as grade III, and 18% patients as grade IV. The mean value of the RLLD/Alb ratio was 4.89 ± 1.49 (range from 2.30 to 8.45). The RLLD/Alb ratio diagnosed the EV employing the cut-off value of 4.01 with 85.3% sensitivity and 68.8% specificity. Furthermore, it was positively correlated with the grading of EV, when this ratio increased the grading of EV increases and vice versa (r = 0.630, p < 0.001). CONCLUSION: The RLLD/Alb ratio is a non-invasive parameter giving exact guidance relevant to the ascertainment of the existence of EV and their grading in chronic liver disease patients.

Investigating the Anticancer Potential of Salvicine as a Modulator of Topoisomerase II and ROS Signaling Cascade.

Salvicine is a new diterpenoid quinone substance from a natural source, specifically in a Chinese herb. It has powerful growth-controlling abilities against a broad range of human cancer cells in both in vitro and in vivo environments. A significant inhibitory effect of salvicine on multidrug-resistant (MDR) cells has also been discovered. Several research studies have examined the activities of salvicine on topoisomerase II (Topo II) by inducing reactive oxygen species (ROS) signaling. As opposed to the well-known Topo II toxin etoposide, salvicine mostly decreases the catalytic activity with a negligible DNA breakage effect, as revealed by several enzymatic experiments. Interestingly, salvicine dramatically reduces lung metastatic formation in the MDA-MB-435 orthotopic lung cancer cell line. Recent investigations have established that salvicine is a new non-intercalative Topo II toxin by interacting with the ATPase domains, increasing DNA-Topo II interaction, and suppressing DNA relegation and ATP hydrolysis. In addition, investigations have revealed that salvicine-induced ROS play a critical role in the anticancer-mediated signaling pathway, involving Topo II suppression, DNA damage, overcoming multidrug resistance, and tumor cell adhesion suppression, among other things. In the current study, we demonstrate the role of salvicine in regulating the ROS signaling pathway and the DNA damage response (DDR) in suppressing the progression of cancer cells. We depict the mechanism of action of salvicine in suppressing the DNA-Topo II complex through ROS induction along with a brief discussion of the anticancer perspective of salvicine.

Devastating dengue outbreak amidst COVID-19 pandemic in Bangladesh: an alarming situation.

Dengue fever is a viral infection caused by Aedes mosquitoes that has recently expanded fast in many of the WHO member states globally. Female mosquitoes, mostly Aedes aegypti and, to a smaller degree, Aedes albopictus, disseminate dengue virus. Dengue fever has been more common in recent decades all across the world, and Bangladesh is no exception. As the COVID-19 outbreak wreaks havoc, the following rise in dengue illnesses has been a source of considerable concern. As the health care has been stretched thin in these dangerous times, the vulnerable population has been left at the mercy of these two viral infections. Lack of knowledge, major legislative changes, poor eradication initiatives, and a lack of financing resources have all contributed to the increase in numbers. Stakeholders and policymakers must begin taking meaningful actions and implementing well-thought-out adjustments immediately, or the situation will worsen, resulting in the loss of thousands of innocent lives.

Development of an in silico multi-epitope vaccine against SARS-COV-2 by précised immune-informatics approaches.

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 has posed an enigmatic challenge to global public health security. Since last year, the mutagenic quality of this virus is causing changes to its genetic material. To prevent those situations, the FDA approved some emergency vaccines but there is no assurance that these will function properly in the complex human body system. In point of view, a short but efficient effort has made in this study to develop an immune epitope-based therapy for the rapid exploitation of SARS-CoV-2 by applying in silico structural biology and advancing immune information strategies. The antigenic epitopes were screened from the Surface, Membrane, Envelope proteins of SARS-CoV-2 and passed through several immunological filters to determine the best possible one. According to this, 7CD4+, 10CD8+ and 5 B-cell epitopes were found to be prominent, antigenic, immunogenic, and most importantly, highly conserved among 128 Bangladeshi and 110 other infected countries SARS-CoV-2 variants. After that, the selected epitopes and adjuvant were linked to finalize the multi-epitope vaccine by appropriate linkers. The immune simulation disclosed that the engineered vaccine could activate both humoral and innate immune responses. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLRs). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, MD simulation was performed within the highest binding affinity complex to observe the stability. Codon optimization and other physicochemical properties revealed that the vaccine would be suitable for a higher expression at cloning level. So, monitoring the overall in silico assessment, we anticipated that our engineered vaccine would be a plausible prevention against COVID-19.

Foxc2CreERT2 knock-in mice mark stage-specific Foxc2-expressing cells during mouse organogenesis.

Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2CreERT2 ) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2CreERT2 ; R26R), the fate of Foxc2 positive (Foxc2+ ) cells was analyzed through LacZ staining at various embryonic stages. We found Foxc2+ cell descendants in the supraoccipital and exoccipital bone in E18.5 embryos, when tamoxifen was administered at embryonic day (E) 8.5. Furthermore, Foxc2+ descendant cranial neural crest cells at E8-10 were restricted to the corneal mesenchyme, while Foxc2+ cell derived cardiac neural crest cells at E6-12 were found in the aorta, pulmonary trunk and valves, and endocardial cushions. Foxc2+ cell descendant contributions to the glomerular podocytes in the kidney were also observed following E6.5 tamoxifen treatment. Our results are consistent with previous reports of Foxc2 expression during early embryogenesis and the Foxc2CreERT2 mouse provides a tool to investigate spatiotemporal roles of Foxc2 and contributions of Foxc2+ expressing cells during mouse embryogenesis.

Pol I-transcribed hepatitis C virus genome RNA replicates, produces an infectious virus and leads to severe hepatic steatosis in transgenic mice.

Patients chronically infected with hepatitis C virus (HCV) are at risk of developing end-stage liver disease and hepatocellular carcinoma. Development of drugs to inhibit hepatocyte damage and a vaccine against HCV is hampered by the lack of a small animal model. We generated mice in which the viral genome RNA was always present in the hepatocytes using a special transgene. Here we show that the HCV genome RNA transcribed by Pol I polymerase can replicate and produce infectious viruses in mice. We obtained a transgenic mouse with 200 copies per haploid which we named the A line mouse. It produced ~ 3 × 10(6) HCV RNA copies/mL serum, which is at the comparable level as patients with chronic HCV infection. This mouse was immunotolerant to HCV and showed hepatic steatosis without any necroinflammation at the age of 6 months or hepatocellular carcinoma at the age of 15 months. Thus, the A line mouse can be used as an animal model for chronic HCV infection. This will enable better study of the abnormalities in metabolism and signal transduction in infected hepatocytes, and development of drugs that cure abnormalities.

Generation and characterization of Tbx1-AmCyan1 transgenic reporter mouse line that selectively labels developing thymus primordium.

Thymus development is a complicated process that includes highly dynamic morphological changes and reciprocal tissue interactions between endoderm-derived epithelial cells of the anterior foregut and neural crest-derived mesenchymal cells. We generated and characterized a Tbx1-AmCyan1 reporter transgenic mouse to visualize thymus precursor cells during early embryonic development. In transgenic embryos, AmCyan1 fluorescence was specifically detected in the endoderm of the developing 3rd and 4th pharyngeal pouches and later in thymus epithelium until E14.5. Cells expressing AmCyan1 that were isolated based on AmCyan1 fluorescence expressed endodermal, thymic, and parathyroid markers, but they did not express neural crest or endothelial markers; these findings indicated that this transgenic mouse strain could be used to collect thymic or parathyroid precursor cells or both. We also showed that in nude mice, which exhibit defects in thymus development, the thymus precursors were clearly labeled with AmCyan1. In summary, these AmCyan1-fluorescent transgenic mice are useful for investigating early thymus development.