Petri Net modelling approach for analysing the behaviour of Wnt/[inline-formula removed] -catenin and Wnt/Ca 2+ signalling pathways in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure and sudden death. The hallmark pathological findings are progressive myocyte loss and fibro fatty replacement, with a predilection for the right ventricle. This study focuses on the adipose tissue formation in cardiomyocyte by considering the signal transduction pathways including Wnt/[inline-formula removed]-catenin and Wnt/Ca2+ regulation system. These pathways are modelled and analysed using stochastic petri nets (SPN) in order to increase our comprehension of ARVC and in turn its treatment regimen. The Wnt/[inline-formula removed]-catenin model predicts that the dysregulation or absence of Wnt signalling, inhibition of dishevelled and elevation of glycogen synthase kinase 3 along with casein kinase I are key cytotoxic events resulting in apoptosis. Moreover, the Wnt/Ca2+ SPN model demonstrates that the Bcl2 gene inhibited by c-Jun N-terminal kinase protein in the event of endoplasmic reticulum stress due to action potential and increased amount of intracellular Ca2+ which recovers the Ca2+homeostasis by phospholipase C, this event positively regulates the Bcl2 to suppress the mitochondrial apoptosis which causes ARVC

Abdominal cystic echinococcosis in Bangladesh: a hospital-based study

Introduction: Cystic echinococcosis (CE) is reported from nearly all geographic areas of Bangladesh, but little information is available on its epidemiologic and clinical features. The aim of this study was to describe the clinical manifestations of hepatic and abdominal CE cases presenting to tertiary referral hospitals in Dhaka, Bangladesh. Methodology: A retrospective study was conducted via chart reviews of hepatic and abdominal CE patients under care at tertiary referral hospitals in Dhaka, Bangladesh, between 2002 and 2011. Age, sex, education level, occupation, urban versus rural residence, drinking water source, history of dog ownership, cyst type and location, and clinical manifestations were recorded for all patients. Results: Of the 130 patients enrolled, 92 (70.8%) were female and 38 (29.2%) were male. The majority of patients were from rural (76.2%) rather than urban (23.8%) areas. All cases were from the northern part of the country, with no cases reported from the south or southeast. Most patients were between 21 and 40 years of age. A total of 119 patients (91.5%) had cysts only in the liver, with the remaining 8.5% having cysts in both the liver and lungs or in the abdominal cavity. Seventy-six (58.5%) of the hepatic cysts were stage CE1, indicating recent infection. Conclusions: Active transmission of Echinococcus granulosus appears to be occurring in Bangladesh, as indicated by the high number of CE1 hepatic cysts seen at tertiary care hospitals. Community ultrasound screening studies are warranted to better define the distribution of cases and risk factors for parasite transmission

High Occurrence of Multidrug-Resistant <i>Escherichia coli</i> Strains in Bovine Fecal Samples from Healthy Cows Serves as Rich Reservoir for AMR Transmission

Objectives: Antibiotics are valuable therapeutics. However, the unwarranted and excessive use of these antimicrobials in food animals and the consequent contamination of the environment have been associated with the emergence and spread of antimicrobial resistance. Continuous surveillance and monitoring of antimicrobial resistance among E. coli isolates is recommended, not only for bovine health but also for public health. This study aims to assess the antimicrobial resistance profile, virulence potential, and genetic characterization of fecal E. coli isolates from healthy cows. Methodology: The in vitro, phenotypic antibiotic resistance of isolates was measured via the Kirby–Bauer disc-diffusion method against twenty-seven antibiotics. The β-lactamase enzymatic activities of the strains were also investigated. For the assessment of virulence potential, fecal E. coli isolates were subjected to several in vitro pathogenicity assays, including biofilm formation ability, blood hemolysis, complement resistance, and growth in human urine. Phylogroup determination and virulence-associated genes were detected via multiplex PCR. Results: In vitro antibiotic resistance profiling showed that 186/200 (93%) of the isolates were multidrug-resistant (MDR), with the highest resistance against penicillin, tetracycline, fluoroquinolone, and macrolide classes of antibiotics. Of particular concern was the phenotypic resistance to colistin in 52/200 isolates (26%), though 16% of the total isolates harbored mcr1, the genetic determinant of colistin. Despite the scarce use of fluoroquinolone, cephalosporin, and carbapenem in the agricultural sector, resistance to these classes was evident due to the presence of extended-spectrum β-lactamase (ESBL) in 41% of E. coli isolates. The β-lactamase genotyping of E. coli isolates showed that 47% of isolates harbored either blaCTX or blaTEM. Approximately 32% of isolates were resistant to serum complement, and their growth in human urine was evident in 18% of isolates, indicating a possible infection of these isolates in high nitrogenous condition. Phylogrouping showed that the most prevalent phylogenetic group among fecal E. coli isolates was phylogroup B1 (57%), followed by phylogroups A (33%), D (6%), and B2 (4%). The most prevalent virulence-associated genes in fecal E. coli were fimH, iss and tatT. Results showed that ten isolates (5%) harbored the stx1 gene, the genetic marker of enterohemorrhagic E. coli. This study provides insights into the antibiotic resistance and virulence profiling of the fecal E. coli isolates from healthy cows. These results emphasize the need for imposing regulations on the proper use of antibiotics and growth promoters in food-producing animals

Advancing seismic resilience: Performance-based assessment of mid-rise and high-rise engineered cementitious composite (ECC) Buildings

Engineering Cementitious Composites (ECC) have received wide attention in recent years due to their enhanced mechanical properties and ductility. These properties offer an opportunity to design structures with significantly improved seismic performance having a low-damage and ductile response. However, existing research studies primarily focus on the performance of ECC at material and member scales, resulting in a knowledge gap regarding its response at the structural level. This study examines the system-level seismic response of buildings designed using ECC and compares their performance with those having conventional reinforced concrete (RC) members. For this purpose, two RC shear wall buildings (7-story and 24-story) were selected as a case study, and their elements were separately designed (for the combined gravity and lateral loads) as RC and ECC elements using the guidelines recommended by the Japan Society of Civil Engineering (JSCE) and ACI (American Concrete Institute)−318–19. The design results show that the requirement of longitudinal steel is reduced by a maximum of 24% in ECC flexural members and by 15% in compression members, in addition to a significant reduction in the required transverse reinforcement as compared to the corresponding RC members. Similarly, owing to improved tensile behavior, the ECC members also exhibited a higher shear capacity than RC members. The detailed nonlinear finite element models of the case study buildings (for both the design cases i.e., ECC and RC) were subjected to monotonic and reversed-cyclic pushover analysis, and nonlinear time history analyses (NLTHA) under a set of selected ground motions. It was observed that ECC structures exhibited significantly improved lateral capacity, revered-cyclic response, and overall seismic performance as compared to the corresponding RC structures. These results demonstrate that ECC can be effectively used to design various members for improved seismic performance of buildings

Amyand's hernia in children

Background: Amyand's Hernia (AH) is a rare entity described as the presence of the vermiform appendix in an inguinal hernial sac. Though its prevalence is three times more in children than adults, owing to the presence of patent processus vaginalis, its occurrence with acute appendicitis is more uncommon in children, especially in infants. Seldom diagnosed correctly ahead of surgical exploration, it is often clinically diagnosed as an incarcerated inguinal hernia or as a case of acute scrotum. The management of such cases depends upon the per-operative findings. Case presentation: In this series, we report four cases of AH treated at King Saud Medical City Hospital Riyadh between 2018 and 2022.All the four patients were male and three of them were infants. Three patients had right sided hernia, while one had bilateral inguinal hernia. One of the patients was diagnosed with strangulated hernia and upon exploration it was AH with acute appendicitis and appendectomy was done. One child had recurrent, irreducible hernia and upon exploration, found appendix densely adherent to the hernial sac. Another patient had early suppurative inflammation at the tip, while the patient with bilateral hernias had appendix adherent to the right hernial sac. In all our cases appendectomy was performed either due to inflammation or adhesions. Conclusion: There is a rarity of this condition and few cases have been reported in the literature. Such cases need to be reported to keep the surgeons aware of this condition and its different manifestations. Herein, we aim to share our experience of four cases of AH with varied presentations and a literature review

Effects of SLC22A2 (rs201919874) and SLC47A2 (rs138244461) genetic variants on Metformin Pharmacokinetics in Pakistani T2DM patients

Objective: To determine the frequencies of single nucleotide polymorphisms rs201919874 and rs138244461 in genes SLC22A2 and SLC47A2 respectively in Pakistani diabetes patients in order to characterise the genetic variants and determine their association with the pharmacokinetics of metformin. Methods: The case-control study was conducted at the International Islamic University, Islamabad, Pakistan, from June 2016 to June 2017, and comprised genotypes of diabetic cases and matching controls which were determined following allele-specific polymerase chain reaction. Cases were further divided into Group A and Group B. The former consisted of diabetics who were on monotherapy of metformin, while the latter consisted of diabetics treated with a combination of metformin and sulfonylureas. In-silico analysis was performed to verify the effect of single nucleotide polymorphisms rs201919874 and rs138244461 on the structure of genes. Association was statistically determined using SPSS 18. Results: Of the 1200 subjects, 800(66.6%) were cases and 400(33.3%) were controls. Among the cases, 400(50%) each were in Group A and Group B. Significant difference was observed in the distribution of rs201919874 between Group A and controls (p<0.05) and between Group B and controls (p<0.05) for heterozygous genotypic frequency and for allelic frequency. Conversely, statistically significant difference was observed in rs138244461 (p<0.05) for all genotypic and allelic frequencies. Genotypes were significantly associated with glycated haemoglobin, random and fasting glucose levels in Group A compared to Group B (p<0.05). In-silico analysis showed that both single nucleotide polymorphisms were expected to create significantly damaging structural changes in domains and helix (p<0.05 each). Conclusions: Both exonic single nucleotide polymorphisms were found to be associated with the pharmacokinetics of metformin

Genetic Engineering Approaches for Enhanced Insect Pest Resistance in Sugarcane

Sugarcane (Saccharum officinarum), a sugar crop commonly grown for sugar production all over the world, is susceptible to several insect pests attack in addition to bacterial, fungal and viral infections leading to substantial reductions in its yield. The complex genetic makeup and lack of resistant genes in genome of sugarcane have made the conventional breeding a difficult and challenging task for breeders. Using pesticides for control of the attacking insects can harm beneficial insects, human and other animals and the environment as well. As alternative and effective strategy for control of insect pests, genetic engineering has been applied for overexpression of cry proteins, vegetative insecticidal proteins (vip), lectins and proteinase inhibitors (PI). In addition, the latest biotechnological tools such as host-induced gene silencing (HIGS) and CRISPR/Cas9 can be employed for sustainable control of insect pests in sugarcane. In this review overexpression of the cry, vip, lectins and PI genes in transgenic sugarcane and their disease resistance potential is described

Palliation of four-wave mixing in optical fibers using improved dsp receiver

A long haul optical communication system (LHOCS) is one of the key resources to fulfill the higher capacity requirements in future communication networks. To launch LHOCS, the system mainly faces high order nonlinear effects. The four-wave mixing (FWM) is one of the major nonlinear effects, which limits the transmission distance. Therefore, in this paper, an advanced duo-binary (DB) modulation scheme-based system is evaluated by employing an improved digital signal processing (IDSP) approach at the receiver side to suppress the FWM effect. In addition, an analytical analysis is also performed for the proposed system. To observe the difference between the IDSP and conventional digital signal processing (DSP), the various performance metrics such as bit error rate (BER), Q-factor, and optical signal-to-noise ratio (OSNR) parameters are evaluated. Variable channel spacing along with polarization mode dispersion (PMD) are analyzed at several ranges of input powers and fiber lengths. The analytical and simulation-based calculations exhibit the effectiveness of the proposed model and hence, FWM effect are compensated to achieve 500 km optical fiber propagation range with a BER below 10−6

Palliation of Four-Wave Mixing in Optical Fibers Using Improved DSP Receiver

A long haul optical communication system (LHOCS) is one of the key resources to fulfill the higher capacity requirements in future communication networks. To launch LHOCS, the system mainly faces high order nonlinear effects. The four-wave mixing (FWM) is one of the major nonlinear effects, which limits the transmission distance. Therefore, in this paper, an advanced duo-binary (DB) modulation scheme-based system is evaluated by employing an improved digital signal processing (IDSP) approach at the receiver side to suppress the FWM effect. In addition, an analytical analysis is also performed for the proposed system. To observe the difference between the IDSP and conventional digital signal processing (DSP), the various performance metrics such as bit error rate (BER), Q-factor, and optical signal-to-noise ratio (OSNR) parameters are evaluated. Variable channel spacing along with polarization mode dispersion (PMD) are analyzed at several ranges of input powers and fiber lengths. The analytical and simulation-based calculations exhibit the effectiveness of the proposed model and hence, FWM effect are compensated to achieve 500 km optical fiber propagation range with a BER below 10−6

Exploring the Associations and Molecular Impacts of miR-146a/rs2910164 and miR-196a2/rs185070757 with Rheumatoid Arthritis in a Pakistani Population

Introduction: MicroRNAs (miRNAs) are a new class of molecules that participate in post-transcriptional regulation of gene expression and hence have been reported to have a crucial role in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of miR-146a rs2910164 (G/C) and miR-196a2 rs185070757 (T/G) with RA susceptibility in Pakistani patients and to bioinformatically predict the molecular function of these miRNAs. Methods: A case-control study on 600 individuals was conducted, including 300 RA patients and 300 matching healthy controls. Genotyping was performed by tetra-primer amplification of refractory mutation system-polymerase chain reaction, and the association between variants and RA was statistically determined using different models. Results: For the variant rs2910164 (G/C) in miR-146a, no difference in genotype distribution was observed between RA cases and controls, as determined using co-dominant (χ2 = 4.33; p = 0.114), homozygous dominant (C/C vs. G/G + C/G) (OR = 0.740 [0.531–1.032]; p = 0.091), homozygous recessive (G/G vs. C/C + G/C) (odds ratio [OR] = 01.432 [0.930–2.206]; p = 0.126), heterozygous (G/C vs. C/C + G/G) (OR = 1.084 [0.786–1.494]; p = 0.682), and additive (OR 0.778 [0.617–0.981]; p = 0.039) models. Similarly, the GT genotype in the rs185070757 (T/G) miR-196a2 variant did not differ between cases and controls with any models (p &gt; 0.05). For the first time, we report no association of miR-146a rs2910164 (G/C) and miR-196a2 rs185070757 (T/G) with RA in a Pakistani population. A subsequent bioinformatic analysis revealed that the CC genotype of miR-146a rs2910164 might have a protective role against RA pathogenesis, with no effect observed with the miR-196a2 rs185070757. Conclusion: Our findings suggest that these miRNAs might have little-to-no impact on the RA pathogenesis in the Pakistani population