Incidence and Temporal Evolution of Delayed Peridevice Leak After Left Atrial Appendage Closure.

BACKGROUND: Peridevice leak (PDL) following left atrial appendage closure (LAAC) portends adverse outcomes. OBJECTIVE: To assess the incidence, predictors, clinical implications, and temporal evolution of PDL following LAAC. METHODS: This single-center retrospective study included all patients who underwent LAAC with Watchman FLX and had no PDL detected at implant. The primary endpoint was incidence of new PDL at initial imaging. The composite secondary endpoint included continued oral anticoagulation after initial imaging, device-related thrombus, stroke or transient ischemic attack, major bleeding, and need for PDL closure at longest follow-up. Temporal evolution of PDL was assessed in patients with available surveillance imaging. RESULTS: Among 355 patients who completed imaging at 47 (IQR 6) days, 139 (39%) had a new PDL with a mean leak size of 3.2±1.4 [median 3.0 (IQR 2.0), and range 1.0-9.0 mm]. Multiple deployment attempts and larger device size were positive predictors of PDL, while increased contrast volume administration was a negative predictor of PDL. The composite secondary endpoint occurred in 42 (30%) and 33 (15%) patients with and without PDL respectively (p<0.001). Among the 139 patients with PDL, 43 (31%) had surveillance imaging where leak size regressed from 3.7±1.8mm at 46 (IQR 7) days to 1.7±2.0mm at 189 (IQR 127) days (p<0.001). The leak size regressed in 33 (77%), remained stable in 4 (9%), and progressed in 6 (14%) cases. CONCLUSION: Despite design improvements, LAAC with Watchman FLX demonstrates significant incidence of PDL with meaningful clinical implications. Regardless of initial size, most leaks regressed over time.

Comparison of Endoscopic Ultrasound and Transabdominal Ultrasound in the Detection of Gallbladder and Common Bile Duct Microlithiasis.

OBJECTIVE: Endoscopic ultrasonography (EUS) is an emerging method with a wide range of potential uses in gastroenterology, including the detection of bile duct stones and the identification of early ductal alterations in suspected patients. This study was designed to compare the diagnostic yield of EUS and transabdominal ultrasound (TUS) in the detection of gallbladder and common bile duct (CBD) microlithiasis. METHOD: Patients with biliary colic with normal initial TUS were the subjects of this prospective study. EUS scan was performed on all recruited patients and linear endoscopes were used for the EUS examination. Cholecystectomy and histological analysis were done in patients within two weeks after EUS revealing cholelithiasis whereas the cases of CBD stone/microlithiasis were confirmed by endoscopic retrograde cholangiopancreatography (ERCP). The mean values of all hematological characteristics were independently determined for males and females and then compared using Student's t-test. For statistical significance, a p-value of 0.05 or below was used. RESULTS: A total of 131 patients, including 77 females and 54 males, with a mean age of 38.41 ± 14.78 years were examined. All 78 (59.5%) individuals who had cholecystectomy were found to have gallstones or microlithiasis as successfully diagnosed by EUS. The sensitivity and specificity of EUS were 92.9% and 100%, respectively, for CBD stones and 98.8% and 100%, respectively, for the detection of gallbladder microlithiasis. The agreement between EUS and TUS was fair for CBD stones (κ = 0.214) and very weak for microlithiasis (κ = -0.093). CONCLUSION: EUS demonstrates a superior yield over TUS in detecting gallbladder stones and CBD microlithiasis, offering a more reliable diagnostic modality. LIMITATION: This was a single-center study.

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease.

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Predicting short-term thromboembolic risk following Roux-en-Y gastric bypass using supervised machine learning.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a widely recognized bariatric procedure that is particularly beneficial for patients with class III obesity. It aids in significant weight loss and improves obesity-related medical conditions. Despite its effectiveness, postoperative care still has challenges. Clinical evidence shows that venous thromboembolism (VTE) is a leading cause of 30-d morbidity and mortality after RYGB. Therefore, a clear unmet need exists for a tailored risk assessment tool for VTE in RYGB candidates. AIM: To develop and internally validate a scoring system determining the individualized risk of 30-d VTE in patients undergoing RYGB. METHODS: Using the 2016-2021 Metabolic and Bariatric Surgery Accreditation Quality Improvement Program, data from 6526 patients (body mass index ≥ 40 kg/m2) who underwent RYGB were analyzed. A backward elimination multivariate analysis identified predictors of VTE characterized by pulmonary embolism and/or deep venous thrombosis within 30 d of RYGB. The resultant risk scores were derived from the coefficients of statistically significant variables. The performance of the model was evaluated using receiver operating curves through 5-fold cross-validation. RESULTS: Of the 26 initial variables, six predictors were identified. These included a history of chronic obstructive pulmonary disease with a regression coefficient (Coef) of 2.54 (P < 0.001), length of stay (Coef 0.08, P < 0.001), prior deep venous thrombosis (Coef 1.61, P < 0.001), hemoglobin A1c > 7% (Coef 1.19, P < 0.001), venous stasis history (Coef 1.43, P < 0.001), and preoperative anticoagulation use (Coef 1.24, P < 0.001). These variables were weighted according to their regression coefficients in an algorithm that was generated for the model predicting 30-d VTE risk post-RYGB. The risk model's area under the curve (AUC) was 0.79 [95% confidence interval (CI): 0.63-0.81], showing good discriminatory power, achieving a sensitivity of 0.60 and a specificity of 0.91. Without training, the same model performed satisfactorily in patients with laparoscopic sleeve gastrectomy with an AUC of 0.63 (95%CI: 0.62-0.64) and endoscopic sleeve gastroplasty with an AUC of 0.76 (95%CI: 0.75-0.78). CONCLUSION: This simple risk model uses only six variables to assist clinicians in the preoperative risk stratification of RYGB patients, offering insights into factors that heighten the risk of VTE events.

Advancements in bacterial chemotaxis: Utilizing the navigational intelligence of bacteria and its practical applications.

The fascinating world of microscopic life unveils a captivating spectacle as bacteria effortlessly maneuver through their surroundings with astonishing accuracy, guided by the intricate mechanism of chemotaxis. This review explores the complex mechanisms behind this behavior, analyzing the flagellum as the driving force and unraveling the intricate signaling pathways that govern its movement. We delve into the hidden costs and benefits of this intricate skill, analyzing its potential to propagate antibiotic resistance gene while shedding light on its vital role in plant colonization and beneficial symbiosis. We explore the realm of human intervention, considering strategies to manipulate bacterial chemotaxis for various applications, including nutrient cycling, algal bloom and biofilm formation. This review explores the wide range of applications for bacterial capabilities, from targeted drug delivery in medicine to bioremediation and disease control in the environment. Ultimately, through unraveling the intricacies of bacterial movement, we can enhance our comprehension of the intricate web of life on our planet. This knowledge opens up avenues for progress in fields such as medicine, agriculture, and environmental conservation.

Bacterial Lipopeptides Are Effective against Pear Fire Blight.

Fire blight, a devastating disease caused by Erwinia amylovora, poses a significant threat to pear and apple trees in Xinjiang province, China. In an effort to combat this pathogen, we isolated 10 bacteria from various components of apple and crabapple trees and conducted screenings to assess their ability to inhibit E. amylovora in vitro. Through biochemical tests and partial 16S rRNA gene sequencing, we identified two promising strains, Priestia megaterium strain H1 and Bacillus subtilis strain I2. These strains were then evaluated for their efficacy in biocontrol under controlled laboratory conditions, focusing on immature fruits and leaves. Remarkably, all selected antagonists exhibited the capability to reduce the severity of the disease on both fruit and leaves. P. megaterium strain H1 and B. subtilis strain I2 exhibited significant reductions in disease incidence on both immature fruits and leaves compared to the control. Specifically, on immature fruits, they achieved reductions of 53.39% and 44.76%, respectively, while on leaves, they demonstrated reductions of 59.55% and 55.53%, respectively. Furthermore, during the study, we detected the presence of lipopeptides, including surfactin, iturins, bacillomycin D, and fengycins, in the methanol extract obtained from these two antagonistic bacteria using thin-layer chromatography (TLC). Based on the results obtained, B. subtilis strain I2 and P. megaterium strain H1 exhibit considerable potential for controlling fire blight. However, further evaluation of their efficacy under natural field conditions is essential to validate their practicality as a biocontrol method.

Autophagy-associated non-coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis.

BACKGROUND: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy-a crucial cellular process for maintaining protein and organelle integrity. METHODS: This review focuses on the role of non-coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. RESULTS: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. CONCLUSION: ncRNAs hold significant therapeutic potential for addressing autophagy-related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy-related ncRNAs and discusses the challenges and prospective directions for developing ncRNA-based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

From oncogenes to tumor suppressors: The dual role of ncRNAs in fibrosarcoma.

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.

Non-coding RNA mediated regulation of PI3K/Akt pathway in hepatocellular carcinoma: Therapeutic perspectives.

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.

The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis.

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.

The Effects of Heavy Metal Pollution on Soil Nitrogen Transformation and Rice Volatile Organic Compounds under Different Water Management Practices.

One of the most concerning global environmental issues is the pollution of agricultural soils by heavy metals (HMs), especially cadmium, which not only affects human health through Cd-containing foods but also impacts the quality of rice. The soil's nitrification and denitrification processes, coupled with the release of volatile organic compounds by plants, raise substantial concerns. In this review, we summarize the recent literature related to the deleterious effects of Cd on both soil processes related to the N cycle and rice quality, particularly aroma, in different water management practices. Under both continuous flooding (CF) and alternate wetting and drying (AWD) conditions, cadmium has been observed to reduce both the nitrification and denitrification processes. The adverse effects are more pronounced in alternate wetting and drying (AWD) as compared to continuous flooding (CF). Similarly, the alteration in rice aroma is more significant in AWD than in CF. The precise modulation of volatile organic compounds (VOCs) by Cd remains unclear based on the available literature. Nevertheless, HM accumulation is higher in AWD conditions compared to CF, leading to a detrimental impact on volatile organic compounds (VOCs). The literature concludes that AWD practices should be avoided in Cd-contaminated fields to decrease accumulation and maintain the quality of the rice. In the future, rhizospheric engineering and plant biotechnology can be used to decrease the transport of HMs from the soil to the plant's edible parts.

Predicting the risk of early intensive care unit admission for patients hospitalized with acute pancreatitis using supervised machine learning.

Background: Acute pancreatitis (AP) is a complex and life-threatening disease. Early recognition of factors predicting morbidity and mortality is crucial. We aimed to develop and validate a pragmatic model to predict the individualized risk of early intensive care unit (ICU) admission for patients with AP. Methods: The 2019 Nationwide Readmission Database was used to identify patients hospitalized with a primary diagnosis of AP without ICU admission. A matched comparison cohort of AP patients with ICU admission within 7 days of hospitalization was identified from the National Inpatient Sample after 1:N propensity score matching. The least absolute shrinkage and selection operator (LASSO) regression was used to select predictors and develop an ICU acute pancreatitis risk (IAPR) score validated by 10-fold cross-validation. Results: A total of 1513 patients hospitalized for AP were included. The median age was 50.0 years (interquartile range: 39.0-63.0). The three predictors that were selected included hypoxia (area under the curve [AUC] 0.78), acute kidney injury (AUC 0.72), and cardiac arrhythmia (AUC 0.61). These variables were used to develop a nomogram that displayed excellent discrimination (AUC 0.874) (bootstrap bias-corrected 95% confidence interval 0.824-0.876). There was no evidence of miscalibration (test statistic = 2.88; P = 0.09). For high-risk patients (total score >6 points), the sensitivity was 68.94% and the specificity was 92.66%. Conclusions: This supervised machine learning-based model can help recognize high-risk AP hospitalizations. Clinicians may use the IAPR score to identify patients with AP at high risk of ICU admission within the first week of hospitalization.

Formulation and characterization of polymeric nanoparticle of Rivastigmine for effective management of Alzheimer's disease.

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer's disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (-11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p < 0.01) reduced brain cholinesterase activity when compared to scopolamine-treated animals. According to the above results, it can be concluded that RIV-loaded PLGA NPs are ideal carriers for delivering the drug at a specific target site in the brain, thus may treat Alzheimer's disease efficiently and improve patient compliance.

Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.

Acute pancreatitis associated with pembrolizumab-induced hypertriglyceridemia.

INTRODUCTION: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela. CASE REPORT: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP. MANAGEMENT AND OUTCOME: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis. DISCUSSION: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities.

The Great Imitator: A Case of Lyme Carditis Mimicking ST Elevation Myocardial Infarction.

Lyme disease, caused by Borrelia burgdorferi and transmitted via Ixodes ticks, is a common vector-borne illness in the United States, with an estimated 476,000 annual cases. While primarily known for its neurological and rheumatological manifestations, Lyme disease can also involve the cardiac system, known as Lyme carditis, which occurs in about 4% to 10% of cases. This case report details a rare instance of Lyme carditis presenting as ST-segment elevation myocardial infarction (STEMI) in a 31-year-old female with no significant medical history. The patient exhibited symptoms of chest pressure and shortness of breath, with laboratory results showing significantly elevated troponin levels and other indicative markers. Notably, cardiac catheterization revealed no coronary occlusion, suggesting an alternative diagnosis to acute coronary syndrome (ACS). Further testing confirmed Lyme carditis through positive serological tests for Lyme-specific IgM antibodies. The case underscores the importance of considering Lyme myopericarditis in differential diagnoses for STEMI in Lyme-endemic areas and in patients without typical risk factors for coronary artery disease. This report aims to increase clinical awareness of this condition, highlighting the need for thorough investigation in atypical cardiac presentations.

Arsenic in the Food Chain in Pakistan: Assessing Risks to Human Health and Ensuring Food Security Through Comprehensive Contamination Mitigation Strategies.

Arsenic is a natural element found in the earth's crust and is extensively present in various environmental components. Anthropogenic activities and a few natural events have generated contaminants that have led to massive environmental pollution, one form of which is arsenic contamination. Arsenic enters the human food chain via contaminated crops, water, seafood, and dairy products. In Pakistan, the increasing concentration of arsenic in the water is causing major health problems. Due to the serious health risks posed by arsenic, it is crucial to design and implement strategies for reducing and preventing the bioaccumulation of arsenic and its entry into the human food chain. There is a need for an institutional framework for arsenic mitigation, accountability, and systemic checks and balances. Targeted short- and long-term policies are required for effective and sustainable management.

Role of gut microbiota in cardiovascular diseases - a comprehensive review.

The connection between cardiovascular illnesses and the gut microbiota has drawn more and more attention in recent years. According to research, there are intricate relationships between dietary elements, gut bacteria, and their metabolites that affect cardiovascular health. In this study, the role of gut microbiota in cardiovascular disorders is examined, with an emphasis on the cardiac consequences brought on by changes in gut microbiota. This essay discusses the gut-heart axis in depth and in detail. It talks about clinical research looking at how soy consumption, probiotic supplements, and dietary changes affected gut microbiota and cardiovascular risk variables. Our goal is to clarify the possible pathways that connect gut microbiota to cardiovascular health and the implications for upcoming treatment approaches. The authors examine the composition, roles, and effects of the gut microbiota on cardiovascular health, including their contributions to hypertension, atherosclerosis, lipid metabolism, and heart failure. Endotoxemia, inflammation, immunological dysfunction, and host lipid metabolism are some of the potential processes investigated for how the gut microbiota affects cardiac outcomes. The research emphasizes the need for larger interventional studies and personalized medicine strategies to completely understand the complexity of the gut-heart axis and its implications for the management of cardiovascular disease. The development of novel treatment strategies and cutting-edge diagnostic technologies in cardiovascular medicine may be facilitated by a better understanding of this axis.

Diagnostic efficacy of hand-held digital refractometer for determining total serum protein in indigenous sheep of Pakistan.

The study was designed to ascertain the diagnostic efficacy of hand-held digital refractometer in determining total protein (TP). The Sipli sheep (n = 128) were grouped as per gender (females = 99, males = 29) and age (G1 = up till 1 year, n = 35; G2 = from 1 to 2 years, n = 63; G3 = above 2 years, n = 30). The results regarding the overall mean (±SE) values for the TPs attained through serum chemistry analyzer (TP1) and hand-held digital refractometer (TP2) were non-significantly (P≥0.05) different (59.2±1.6g/L and 59.8±0.5g/L, respectively). However, the reference intervals (RIs) were quite different for the two TPs being 45.1-95.7g/L and 57.0-67.0g/L for TP1 and TP2, respectively. Similar results were seen for gender-wise and group-wise results. On the contrary, the results regarding correlation coefficient and logilinear regression showed a negative correlation between the two TPs (r = -0.0244) with an adjusted r-square of 0.059 (5.9% probability). Furthermore, the three tests implied to assess the level of agreement between the two methods (Cronbach alpha, Intraclass correlation coefficient, and Bland & Altman test) revealed least agreement between the two methods. In a nutshell, the results of TP through digital refractometer were not in concordance with those attained through serum chemistry analyzer. However, it can cautiously be used if these results are compared with relevant corrected RIs.

Pharmacological evaluation and phytochemical profiling of butanol extract of L. edodes with in- silico virtual screening.

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm-1 to 5000 cm-1 respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.