Prefrontal cortex hemodynamic activity during a test of lower extremity functional muscle strength in children with cerebral palsy: A functional near-infrared spectroscopy study.

Children with cerebral palsy (CP) exhibit impaired motor control and significant muscle weakness due to a brain lesion. However, studies that assess the relationship between brain activity and performance on dynamic functional muscle strength assessments in CP are needed. The aim of this study was to determine the effect of a progressive lateral step-up test on prefrontal cortex (PFC) hemodynamic activity in children with CP. Fourteen ambulatory children with spastic CP (Gross Motor Function Classification System level I; 5-11 y) and 14 age- and sex-matched typically developing control children completed a progressive lateral step-up test at incremental step heights (0, 10, 15 and 20 cm) using their non-dominant lower limb. Hemodynamic activity in the PFC was assessed using non-invasive, portable functional neuroimaging (functional near-infrared spectroscopy). Children with CP completed fewer repetitions at each step height and exhibited lower PFC hemodynamic activity across step heights compared to controls. Lower PFC activation in CP was maintained after statistically controlling for the number of repetitions completed at each step height. PFC hemodynamic activity was not associated with LSUT task performance in children with CP, but a positive relationship was observed in controls at the most challenging 20 cm step height. The results suggest there is an altered PFC recruitment pattern in children with CP during a highly dynamic test of functional strength. Further studies are needed to explore the mechanisms underlying the suppressed PFC activation observed in children with CP compared to typically developing children.

Retroperitoneal liposarcoma: Case of a giant tumour inside the abdomen.

Retroperitoneal liposarcomas are rare malignant tumours that often grow rapidly in size and become symptomatic lat e in t he disease course, posing diagnostic a nd therapeutic challenges. Although abdominal imaging can rel iab ly diagnose the tumour, definitive diagnosis is only p ossib le th rough bio psy af ter surgical excision , w hich remains the primary treatment modality for these tumours. Long- term sur v ival is p rimarily determ ined throu gh histologic grade and post-resection tumour margins. We report t he case of a 43-year-o ld male patient, see n at Dr Ruth KM Pfau Hospital Karachi, who under went successful surgical excision for a well-differentiated retroperitoneal liposarcoma an d had no rad io gr aphic evidence o f local recurrence at both 3 and 12-month follow-ups.

Mutual Coupling Reduction in MIMO DRA through Metamaterials.

A single negative metamaterial structure with hexagonal split-ring resonators (H-SRRs) is inserted within a two-port multiple-input multiple-output (MIMO) dielectric resonator antenna (DRA) in order to achieve a reduction of mutual coupling between closed multiple antenna elements. Between closed, tightly coupled, high-profile antenna elements, the single negative magnetic inclusions (H-SRRs) are embedded. By incorporating magnetic structures within antenna elements, the mutual coupling is significantly diminished. Mutual coupling reduction is attained by inserting an array of hexagonal split-ring resonators between the inter-spacing elements. An operative approach for the reduction of the mutual coupling between two × two MIMO DRAs initially operating at 5.2-GHz band is provided. To make the simulated design replica of the fabricated prototype, an air gap is introduced between the substrate, DRs, and H-SSRs. The addition of the air gap shifts the simulated results to 5.9 GHz, which closely resembles the measured values. The mutual coupling reduction is realized by integrating a meta-surface amid the two × two MIMO DRAs, which are settled in the H-plane. The meta-surface embraces an array of hexagonal split-ring resonator (H-SRR) cells that are unified along the E-plane. The H-SRR structure is designed to offer band-stop functionality within the antenna bandwidth. The proposed design has an overall dimension of 40 × 58.3 × 4.75 mm3 (1.5λ × 1.02λ × 0.079λ). By stacking the DRA with a one × three array of H-SRR unit cells, a 30 dB reduction in the mutual coupling level is attained without compromising on the antenna performance. The corresponding mutual impedance of the MIMO DRA is better than 30 dB over 5.9-6.1 GHz operating bandwidth. The proposed design has a DG of 10 db, ECC < 0.02, CCL < 0.02 bits/s/Hz, and an MEG of 0 dB. The overall design has a promising performance, which shows its suitability for the target wireless application.

A Novel Densely Packed 4 × 4 MIMO Antenna Design for UWB Wireless Applications.

In this article, a compact 4-port UWB (Ultra-Wide Band) MIMO (Multiple Input Multiple Output) antenna is proposed. A low profile FR-4 substrate is used as a dielectric material with the dimensions of 58 × 58 mm2 (0.52λ × 0.52λ) at 2.8 GHz and a standard thickness of 1.6 mm. The proposed design characterizes an impedance bandwidth starting from 2.8 to 12.1 GHz (124.1%). Each of the four elements of the proposed MIMO antenna configuration consists of a monopole antenna with PG (partial ground) that has a slot at its center. The corner of each patch (radiator) and ground slot are rounded for impedance matching. Each unit cell is in an orthogonal orientation, forming a quad-port MIMO antenna system. For reference, the partial ground of each unit cell is connected meticulously with the others. The simulated results of the proposed quad-port MIMO antenna design were configured and validated by fabrication and testing. The proposed Quad-port MIMO design has a 6.57 dBi peak gain and 97% radiation efficiency. The proposed design has good isolation below 15 dB in the lower frequency range and below 20 dB in the higher frequency range. The design has a measured ECC (Envelop Correlation Co-efficient) of 0.03 and DG (Diversity Gain) of 10 dB. The value of TARC (Total Active Reflection Coefficient) over the entire operating band is less than 10 dB. Moreover, the design maintained CCL (Channel Capacity Loss) < 0.4 bits/sec/Hz and MEG (Mean Effective Gain) < 3 dB. Based on the obtained results, the proposed design is suitable for the intended high data rate UWB wireless communication portable devices.

Breakthrough COVID-19 infections - Analyzing our experience.

Objective: There are many cases of post-vaccination COVID-19 globally. Also, literature on serum antibodies after vaccination is abundant. Our research focuses on breakthrough infections reported at our institution during the third wave of COVID-19. Methods: A total of 177 people recruited at the Indus Hospital Karachi between May to September 2021 with COVID-19 infection were divided into vaccinated, partially vaccinated, and unvaccinated cohorts. Furthermore, a subset of the vaccinated cohort was tested for anti-NP and anti-S antibodies. Results: There were 119 patients with breakthrough infection, however, 74% had mild symptoms. The antibodies against NP and S were found at a higher level in those who had a breakthrough infection in comparison to healthy vaccinated controls. Conclusion: Vaccination does not prevent disease but does confer some immunity causing less severe infection.

Integrated analysis of long-noncoding RNA and circular RNA expression in Peste-des-Petits-Ruminants Virus (PPRV) infected marmoset B lymphocyte (B95a) cells.

Peste-des-Petits-Ruminants (PPR) or goat plague is an important viral disease of sheep and goats caused by the small ruminant morbilli virus or PPR virus (PPRV). Long non coding RNAs (lncRNA) and circular RNAs (circRNA) play a pivotal role in several biological processes including regulation of virus-host interactions. The present study explored the expression of lncRNA, circRNA and their functions in PPRV infected B-lymphocyte (B95a) cells. The results revealed a total of 4531 lncRNA and 2348 circRNA expression in both mock and PPRV infected samples. Analysis of differentially expressed (DE) RNA identified 123 DE-lncRNA and 39 DE-circRNA as significantly dysregulated. Functional analysis of cis-target genes of DE-lncRNA indicated activation of TCF dependent WNT signaling and PKN1 stimulated transcription process. Interactions (sponging) of microRNA (miRNA) revealed 344 DE-lncRNA-miRNA and 93 DE-circRNA-miRNA pairs. The competing endogenous RNA (ceRNA) network of lncRNA/circRNA-miRNA-mRNA in PPRV infected B95a cells was represented by 69 ceRNA pairs. We validated the DE-circRNA by targeted amplification and sequencing of back spliced junctions (BSJs). The present study revealed a profile of lncRNA, circRNA and their potential ceRNA network in PPRV infection. The results provide insight for better understanding of PPRV-host interactions.

Effect of acute heat shock on stress gene expression and DNA methylation in zebu (Bos indicus) and crossbred (Bos indicus × Bos taurus) dairy cattle.

Environmental temperature is one of the major factors to affect health and productivity of dairy cattle. Gene expression networks within the cells and tissues coordinate stress response, metabolism, and milk production in dairy cattle. Epigenetic DNA methylations were found to mediate the effect of environment by regulating gene expression patterns. In the present study, we compared three Indian native zebu cattle, Bos indicus (Sahiwal, Tharparkar, and Hariana) and one crossbred Bos indicus × Bos taurus (Vrindavani) for stress gene expression and differences in the DNA methylation patterns. The results indicated acute heat shock to cultured PBMC affected their proliferation, stress gene expression, and DNA methylation. Interestingly, expressions of HSP70, HSP90, and STIP1 were found more pronounced in zebu cattle than the crossbred cattle. However, no significant changes were observed in global DNA methylation due to acute heat shock, even though variations were observed in the expression patterns of DNA methyltransferases (DNMT1, DNMT3a) and demethylases (TET1, TET2, and TET3) genes. The treatment 5-AzaC (5-azacitidine) that inhibit DNA methylation in proliferating PBMC caused significant increase in heat shock-induced HSP70 and STIP1 expression indicating that hypomethylation facilitated stress gene expression. Further targeted analysis DNA methylation in the promoter regions revealed no significant differences for HSP70, HSP90, and STIP1. However, there was a significant hypomethylation for BDNF in both zebu and crossbred cattle. Similarly, NR3C1 promoter region showed hypomethylation alone in crossbred cattle. Overall, the results indicated that tropically adapted zebu cattle had comparatively higher expression of stress genes than the crossbred cattle. Furthermore, DNA methylation may play a role in regulating expression of certain genes involved in stress response pathways.

Role of Marek's Disease Virus (MDV)-Encoded US3 Serine/Threonine Protein Kinase in Regulating MDV Meq and Cellular CREB Phosphorylation.

Marek's disease (MD) is a neoplastic disease of chickens caused by Marek's disease virus (MDV), a member of the subfamily Alphaherpesvirinae Like other alphaherpesviruses, MDV encodes a serine/threonine protein kinase, US3. The functions of US3 have been extensively studied in other alphaherpesviruses; however, the biological functions of MDV US3 and its substrates have not been studied in detail. In this study, we investigated potential cellular pathways that are regulated by MDV US3 and identified chicken CREB (chCREB) as a substrate of MDV US3. We show that wild-type MDV US3, but not kinase-dead US3 (US3-K220A), increases CREB phosphorylation, leading to recruitment of phospho-CREB (pCREB) to the promoter of the CREB-responsive gene and activation of CREB target gene expression. Using US3 deletion and US3 kinase-dead recombinant MDV, we identified US3-responsive MDV genes during infection and found that the majority of US3-responsive genes were located in the MDV repeat regions. Chromatin immunoprecipitation sequencing (ChIP-seq) studies determined that some US3-regulated genes colocalized with Meq (an MDV-encoded oncoprotein) recruitment sites. Chromatin immunoprecipitation-PCR (ChIP-PCR) further confirmed Meq binding to the ICP4/LAT region, which is also regulated by US3. Furthermore, biochemical studies demonstrated that MDV US3 interacts with Meq in transfected cells and MDV-infected chicken embryonic fibroblasts in a phosphorylation-dependent manner. Finally, in vitro kinase studies revealed that Meq is a US3 substrate. MDV US3 thus acts as an upstream kinase of the CREB signaling pathway to regulate the transcription function of the CREB/Meq heterodimer, which targets cellular and viral gene expression.IMPORTANCE MDV is a potent oncogenic herpesvirus that induces T-cell lymphoma in infected chickens. Marek's disease continues to have a significant economic impact on the poultry industry worldwide. US3 encoded by alphaherpesviruses is a multifunctional kinase involved in the regulation of various cellular pathways. Using an MDV genome quantitative reverse transcriptase PCR (qRT-PCR) array and chromatin immunoprecipitation, we elucidated the role of MDV US3 in viral and cellular gene regulation. Our results provide insights into how viral kinase regulates host cell signaling pathways to activate both viral and host gene expression. This is an important step toward understanding host-pathogen interaction through activation of signaling cascades.

Assessing the determinants of intentions and behaviors of organizations towards a circular economy for plastics.

The production and consumption of plastics, although inevitable in our modern life, are predominantly unsustainable and inefficient. Hence, the concept of a circular economy for plastics has been proposed as a sustainable approach to thrive both economy and our modern life. To implement a circular economy for plastics, an understanding of both individuals' and organizations' behaviors is needed since psychological effects often undermine technical solutions. We particularly focus on organizations' behaviors since commercial plastic waste has not been thoroughly investigated compared to household plastic waste. Using the Theory of Planned Behavior (TPB) and Partial Least Squares Structural Equation Modeling (PLS-SEM), we assess the determinants of intentions and behaviors of 637 organizations in Belgium towards a circular economy for plastics. Our PLS-SEM analysis support that attitudes, subjective norms, and perceived behavioral control of decision makers positively influence organizations' intentions to implement best practices of plastic recycling. Furthermore, organizations' intentions, perceived behavioral control, pressures, and enablers positively, whereas barriers negatively, influence organizations' behaviors. Our study shows that most organizations have positive intentions, yet they seem to be failing in implementing best practices of plastic recycling due to some critical barriers. To overcome this intention-behavior gap and to attain a circular economy for plastics, our study suggests some measures.

Assessment of caregiver burden of patients receiving dialysis treatment in Rawalpindi.

OBJECTIVE: To determine the burden on the caregivers of patients receiving dialysis treatment. METHODS: This cross-sectional study was carried out in four different dialysis centres of Rawalpindi, Pakistan, from June 1 to December1, 2015, and comprised attendants of patients receiving dialysis. The data was collected from the attendants of patients receiving dialysis, and caregiver burden was measured using the Zarit Burden Interview questionnaire. SPSS 22 was used for data analysis. RESULTS: Of the 164 subjects, 97(59%) were females. The majority of caregivers reported stress for caring (2.28±1.31), patients asking for more help than needed (2.14±1.13), health problems (1.03±1.11), financial constraints (1.70±1.15) and little time for self-care (2.15±1.21). Besides, 107(65%) caregivers perceived the burden of their patients as mild to moderate. A positive correlation was found between the duration of a person on dialysis, daily hours of care-giving and the total burden score of his/her caregiver (p<0.05 each). CONCLUSIONS: Care-giving can create enormous burdens on caregivers, affecting their physical and psychological health.

Augmentation of oral submucous fibrosis by NSAIDs in the presence of risk factors.

Various Risk factors initiate Submucous fibrosis which may be augmented by NSAIDs. A number of animal studies on their mechanism indirectly support it especially regarding alterations in prostaglandin synthesis. This study has been designed to find association of these drugs with Oral Submucous fibrosis in the presence of risk factors. Newly diagnosed patients of Oral Sub mucous fibrosis were recruited for this study who attended Dental Department of Karachi Medical and Dental College from July 1 till Dec 31, 2013.A structured interview and medical record of each patient was used to determine the demographic profile, any addiction, previous and present illnesses and drug (s) used. Through examination of Oral cavity was carried out to access the severity of disease as per modified Khanna & Andrade Classification (1995). Statistical Analysis was done by SPSS 15. Total 102 patients were recruited from dental OPD as per criteria of inclusion. Among these patients 36 (49.31%) were using NSAIDs in which Acetaminophen (30.55%), Acetylsalicylic acid (25.00%) and Diclophenac (19.44%) were 1st, 2nd and 3rd most common drugs. Data shows that 14 patients (28.88%) had mild and 22(61.11%) had sever fibrosis which was significantly high (P<0.05). Mild fibrosis was seen in 05 (45.46%) and Sever fibrosis in 06 (54.54%) out of total 11 patients who were using NSAIDSs since less than or equal to 6 months. Similarly mild fibrosis was seen in 09 (36.00%) and Sever fibrosis in 16 (64.00%) out of total 25 patients who were on NSAIDs since more than 6 months. No statistical significant difference (P>0.05) in severity of fibrosis is seen in patients who were using NSAIDs since less than or equal to 6 months but statistical significant difference (P<0.05) in severity of fibrosis is seen in patients who on these drugs since more than 6 months. Addiction burden was calculated by Average Duration x Average Frequency, which was 92.72 for Pan, 88.88 for Supari and 61.30 for Miscellaneous. No statistically significant difference (P>0.05) was seen in addiction burden of various substances in these patients. An association of NSAIDs with Oral Sub mucous fibrosis exists. The pathology is augmented if these drugs are used in the presence of risk factors. Therefore these drugs should not be prescribed to these patients until a clear benefit is not targeted.

Reduction of Hospital-Acquired Infections Through a Nursing Education Program: A Quality Improvement Project on the Sensitization of Nursing Staff Toward Infection Control in Neonates.

Background This study aimed to reduce hospital-acquired infections (HAIs) by at least 50% in our unit through a nursing education program to sensitize the nursing staff toward infection control in neonates. Methodology This pre- and post-intervention observational study was conducted in Liaquat National Hospital's Neonatal Intensive Care Unit (NICU) from October 2021 until March 2023. This observational study was conducted in three phases. In phase I (pre-implementation), all neonates with suspected HAIs were included. In phase II (implementation), the nursing staff dedicated to the NICU were trained. In phase III (post-implementation), all neonates with suspected HAIs were included. Culture-proven bloodstream infections (BSIs), urinary tract infections (UTIs), and ventilator-associated pneumonia (VAP) were the three types of HAIs. The nursing scoring was done by the principal investigator based on a questionnaire. The Shapiro-Wilk test was used to evaluate the normality of all quantitative data across all phases. Results In the pre-implementation phase, there were 24 (10.8%) HAIs, among which 19 (8.6%) were BSIs, one (0.5%) was a catheter-associated urinary tract infection (CAUTI), and seven (3.2%) were VAP. Whereas in the post-implementation phase, there were 12 (5%) HAIs, among which 10 (4.1%) were BSIs, none were CAUTIs, and five (2.1%) were VAP. There was a significant reduction of HAIs in the post-implementation phase (p < 0.01). The difference in the knowledge, assessment, and practice was statistically significant in the post-implementation phase (p < 0.01). Conclusions We established a successful cost-effective intervention to improve the awareness and compliance of NICU nurses with infection control practices. This helped us in reducing HAIs in our NICU.

Personalized and uncertainty-aware coronary hemodynamics simulations: From Bayesian estimation to improved multi-fidelity uncertainty quantification.

Background: Non-invasive simulations of coronary hemodynamics have improved clinical risk stratification and treatment outcomes for coronary artery disease, compared to relying on anatomical imaging alone. However, simulations typically use empirical approaches to distribute total coronary flow amongst the arteries in the coronary tree, which ignores patient variability, the presence of disease, and other clinical factors. Further, uncertainty in the clinical data often remains unaccounted for in the modeling pipeline. Objective: We present an end-to-end uncertainty-aware pipeline to (1) personalize coronary flow simulations by incorporating vessel-specific coronary flows as well as cardiac function; and (2) predict clinical and biomechanical quantities of interest with improved precision, while accounting for uncertainty in the clinical data. Methods: We assimilate patient-specific measurements of myocardial blood flow from clinical CT myocardial perfusion imaging to estimate branch-specific coronary artery flows. Simulated noise in the clinical data is used to estimate the joint posterior distributions of the model parameters using adaptive Markov Chain Monte Carlo sampling. Additionally, the posterior predictive distribution for the relevant quantities of interest is determined using a new approach combining multi-fidelity Monte Carlo estimation with non-linear, data-driven dimensionality reduction. This leads to improved correlations between high- and low-fidelity model outputs. Results: Our framework accurately recapitulates clinically measured cardiac function as well as branch-specific coronary flows under measurement noise uncertainty. We observe substantial reductions in confidence intervals for estimated quantities of interest compared to single-fidelity Monte Carlo estimation and state-of-the-art multi-fidelity Monte Carlo methods. This holds especially true for quantities of interest that showed limited correlation between the low- and high-fidelity model predictions. In addition, the proposed multi-fidelity Monte Carlo estimators are significantly cheaper to compute than traditional estimators, under a specified confidence level or variance. Conclusions: The proposed pipeline for personalized and uncertainty-aware predictions of coronary hemodynamics is based on routine clinical measurements and recently developed techniques for CT myocardial perfusion imaging. The proposed pipeline offers significant improvements in precision and reduction in computational cost.

Perioperative sildenafil therapy in pulmonary hypertension associated with congenital cardiac disease: An updated meta-analysis.

To provide an updated meta-analysis to evaluate the efficacy and safety of sildenafil on pediatric patients with pulmonary hypertension (PH) associated with congenital heart disease (CHD). To assess the efficacy and safety of sildenafil, five outcomes, time duration of post-operative need for mechanical ventilation, time duration of post-operative ICU stay, length of hospitalization (LOH), the incidence of mortalities and pulmonary arterial pressure to aortic pressure ratio (PAP/AoP) were regarded as primary efficacy outcomes. Standardized mean difference (SMD) was calculated for continuous data. In comparison to the control group (CG), there was a significant decrease in the time duration of ICU stay in the sildenafil group (SG) (SMD = -0.61 [95% CI -1.17, 0.04]; P < 0.01, I2 = 85%). Length of hospitalization was assessed in the sildenafil and control groups (SMD = -0.18 [95% CI -0.67, 0.31] P = 0.05, I2 = 62%). However, there was no significant difference seen in mortality rates between the SG and CG (SMD = 0.53 [ 95% CI 0.13, 2.17] p = 0.61, I2 = 0%), in the time duration of postoperative mechanical ventilation between the SG and CG (SMD = -0.23 [95% CI -0.49, 0.03] p = 0.29, I2 = 19%), or PAP/AoP ratio between the SG and CG (SMD = -0.42 [95% CI -1.35, 0.51] P < 0.01, I2 = 90%). Based on our analysis, sildenafil has little to no effect in reducing postoperative morbidity and mortality due to PH in infants and children with CHD.

Genome-wide DNA methylation profiles regulate distinct heat stress response in zebu (Bos indicus) and crossbred (Bos indicus × Bos taurus) cattle.

Epigenetic variations result from long-term adaptation to environmental factors. The Bos indicus (zebu) adapted to tropical conditions, whereas Bos taurus adapted to temperate conditions; hence native zebu cattle and its crossbred (B indicus × B taurus) show differences in responses to heat stress. The present study evaluated genome-wide DNA methylation profiles of these two breeds of cattle that may explain distinct heat stress responses. Physiological responses to heat stress and estimated values of Iberia heat tolerance coefficient and Benezra's coefficient of adaptability revealed better relative thermotolerance of Hariana compared to the Vrindavani cattle. Genome-wide DNA methylation patterns were different for Hariana and Vrindavani cattle. The comparison between breeds indicated the presence of 4599 significant differentially methylated CpGs with 756 hypermethylated and 3845 hypomethylated in Hariana compared to the Vrindavani cattle. Further, we found 79 genes that showed both differential methylation and differential expression that are involved in cellular stress response functions. Differential methylations in the microRNA coding sequences also revealed their functions in heat stress responses. Taken together, epigenetic differences represent the potential regulation of long-term adaptation of Hariana (B indicus) cattle to the tropical environment and relative thermotolerance.

Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-ß agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom's use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) -4.61, 95% CI -6.77 to -2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74-3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20-4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

Factor Xa inhibitors vs. warfarin in patients with Hughes syndrome: a systematic review and meta-analysis of randomized controlled trials.

Background: The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa inhibitors in patients with Hughes syndrome. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing 8 efficacy and safety of warfarin and factor Xa inhibitors in patients with Hughes syndrome. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among 10 outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate 11 relative risks (RRs) with 95% CIs. Results: The analysis included 625 patients from four RCTs and one post-hoc analysis. Meta-analysis showed a statistically non-significant difference between factor Xa inhibitors and warfarin in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P=0.11, I2=50%]. Consistent results were revealed among patients with a previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P=0.75, I2=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P=0.31, I2=15%] and patients who were triple antiphospholipid antibodies (aPL) positive [RR 4.12 (95% CI 0.46, 37.10); 21 P=0.21, I2=58%]. Factor Xa inhibitors were significantly associated with an increased risk of stroke [RR 8.51 (95% CI 2.35, 13.82); P=0.47, I2=0%]. Conclusion: Factor Xa inhibitors exhibited an increased risk of stroke among patients with Hughes syndrome. In addition, although not significant, the higher RRs among patients on factor Xa inhibitors may indicate a higher risk of thrombotic events associated with factor Xa inhibitors.

Insights into Covid-19 mortality: A comprehensive study of cardiovascular sensitivity, gender, race, and geography trends in the United States (2020-2023).

This investigation meticulously explores the evolving landscape of Covid-19-related mortality in the United States from 2020 to 2023. Leveraging the comprehensive CDC WONDER database, the study conducts a detailed analysis of age-adjusted mortality rates (AAMRs), considering various demographic and regional parameters. The identified pattern illustrates an initial surge in AAMRs from 2020 to 2021, followed by a subsequent decline until 2023. Notably, there is a discernible reduction in AAMRs for both the elderly (85 years and older) and infants (below one year). Within specific demographic segments, heightened AAMRs are observed among NH American Indian or Alaska Native individuals, men, and residents in particular states and regions. Emphasizing the significant impact of Covid-19 on cardiovascular health, the study underscores increased mortality rates associated with the cardiovascular and respiratory systems. AAMR rates were standardized per 100,000 population, providing a comparative metric. Noteworthy states with elevated AAMRs include Mississippi, Oklahoma, Kentucky, New Mexico, and Alabama, with the Southern region exhibiting the highest AAMR. The research sheds light on demographic and regional disparities in Covid-19-related mortality, calling for intensified efforts in prevention and treatment strategies. These findings, offering nuanced insights, serve as a guide for strategic public health initiatives to mitigate the multifaceted repercussions of the pandemic, especially among vulnerable populations.

Cloning of a very virulent plus, 686 strain of Marek's disease virus as a bacterial artificial chromosome.

Bacterial artificial chromosome (BAC) vectors were first developed to facilitate propagation and manipulation of large DNA fragments. This technology was later used to clone full-length genomes of large DNA viruses to study viral gene function. Marek's disease virus (MDV) is a highly oncogenic herpesvirus that causes rapid induction of T-cell lymphomas in chickens. Based on the virus's ability to cause disease in vaccinated chickens, MDV strains are classified into pathotypes, with the most virulent strains belonging to the very virulent plus (vv+) pathotype. Here we report the construction of BAC clones of 686 (686-BAC), a vv+ strain of MDV. Transfection of DNA isolated from two independent clones into duck embryo fibroblasts resulted in recovery of infectious virus. Pathogenesis studies showed that the BAC-derived 686 viruses were more virulent than Md5, a vv strain of MDV. With the use of a two-step red-mediated mutagenesis process, both copies of viral interleukin 8 (vIL-8) were deleted from the MDV genome, showing that 686-BACs were amenable to mutagenesis techniques. The generation of BAC clones from a vv+ strain of MDV is a significant step toward understanding molecular basis of MDV pathogenesis.