The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

Amentoflavone mediated hepatoprotection to counteract paraquat instigated hepatotoxicity via modulating Nrf2/keap1 pathway: A biochemical, inflammatory, apoptotic and histopathological study.

Paraquat (PQ) is a ubiquitous and water-soluble herbicide which has potential to cause systematic poisoning. PQ intoxication is known to be associated with various clinical complications including hepatotoxicity. Amentoflavone (AMF) is an active phenolic compound that exhibits a broad range of biological as well as pharmacological activities. This study was designed to determine the hepato-protective potential of AMF against PQ instigated hepatotoxicity in rats. Forty-eight rats were distributed into four groups such as control group, PQ-treated group (5 mg/kg), PQ (5 mg/kg) + AMF (40 mg/kg) exposed group and AMF (40 mg/kg) only supplemented group. It was revealed that PQ exposure reduced nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidative genes expression whereas increase the expression of Kelch-like ECH-associated protein 1(Keap1). Besides, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), glutathione peroxidase (GPx), Heme- oxygenase-1 (HO-1) & glutathione (GSH) content. Furthermore, the levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were increased. In addition, PQ significantly increased the hepatic serum enzymes including alkaline phosphatase (ALP), aspartate transaminase (AST), & alanine transaminase (ALT) along with inflammatory biomarkers levels such as tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin-6 (IL-6), interleukin 1beta (IL-1ß), & cyclo­oxygenase-2 (COX-2) activity. PQ intoxication increased the expressions of pro-apoptotic markers i.e., Bcl-2-associated X protein (Bax) & Cysteine-aspartic protease-3 (Caspase-3) while reducing the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Furthermore, PQ intoxication prompted various histopathological impairments. However, the co-administration of AMF significantly improved the abovementioned hepatic damages induced by PQ. The present study indicated that AMF may be an effective therapeutic candidate to mitigate PQ provoked hepatic impairments due to its anti-apoptotic, antioxidant & anti-inflammatory properties.

Universal 1H Spin-Lattice NMR Relaxation Features of Sugar-A Step towards Quality Markers.

1H fast field-cycling and time-domain nuclear magnetic resonance relaxometry studies have been performed for 15 samples of sugar of different kinds and origins (brown, white, cane, beet sugar). The extensive data set, including results for crystal sugar and sugar/water mixtures, has been thoroughly analyzed, with a focus on identifying relaxation contributions associated with the solid and liquid fractions of the systems and non-exponentiality of the relaxation processes. It has been observed that 1H spin-lattice relaxation rates for crystal sugar (solid) vary between 0.45 s-1 and 0.59 s-1, and the relaxation process shows only small deviations from exponentiality (a quantitative measure of the exponentiality has been provided). The 1H spin-lattice relaxation process for sugar/water mixtures has turned out to be bi-exponential, with the relaxation rates varying between about 13 s-1-17 s-1 (for the faster component) and about 2.1 s-1-3.5 s-1 (for the slower component), with the ratio between the amplitudes of the relaxation contributions ranging between 2.8 and 4.2. The narrow ranges in which the parameters vary make them a promising marker of the quality and authenticity of sugar.

Opioid Exposure Differentially Impacts Esophageal Body Contraction Over the Lower Esophageal Sphincter.

BACKGROUND & AIMS: Studies with limited sample sizes have investigated association of chronic opioid use with motility disorders of esophagogastric junction and esophageal body peristalsis. Our aims were to use a large cohort of patients to assess (1) the impact of opioid exposure on clinical and manometric characteristics, and (2) the association of opioid exposure with higher long-term symptom burden. METHODS: Patients recruited from a tertiary medical center who underwent high-resolution manometry (HRM) between 2007 and 2018 were included. Demographics, opiate exposure, clinical symptoms, and HRM parameters were compared. Patient-Reported Outcomes Measurement Information System-Gastrointestinal swallowing domain (PROMIS-GI swallowing domain) and Eckardt score were administered via phone interviews in patients with hypercontractile esophagus (HE) or distal esophageal spasm (DES) to determine long-term symptom burden between opioid and nonopioid users. RESULTS: Our cohort included 4075 patients (869 with opiate exposure with median morphine milligram equivalent [interquartile range] of 30 [10-45]). Patients in the opioid group were significantly more likely to have dysphagia (65% vs 51%, P < .01) and diagnosis of DES (11% vs 5%, P < .01) and HE (9% vs 3%, P < .01). Partial opioid agonists were not associated with motility abnormalities. Patients on opioids had significantly higher symptom burden on median (interquartile range) follow-up of 8.9 years (5.8-10.4) post manometric diagnosis with median PROMIS-GI swallowing domain score of 21.5 (17-25) compared with the nonopioid group at 15 (9.8-21, P = .03). CONCLUSIONS: Nearly 2 of 3 patients with opioid exposure undergoing HRM have dysphagia and more than 25% of them with dysphagia as the primary symptom have a diagnosis of either DES or HE. Opioid users with spastic disorders have higher symptom burden long-term compared with nonopioid users.

Pattern, frequency and factors associated with inappropriate high dosing in chronic kidney disease patients at a tertiary care hospital in Pakistan.

BACKGROUND: Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients. METHODS: This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m2). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant. RESULTS: The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses. CONCLUSION: The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.

Hypertriglyceridaemia Induced Pancreatitis Management: A Case Report.

Acute pancreatitis results in high morbidity and mortality. Gallstones and alcoholism are considered leading causes of acute pancreatitis. However, increasing prevalence of obesity, diabetes and lifestyle choices has resulted in Hypertriglyceridaemia induced pancreatitis (HTAP) becoming more common. HTAP is said to be more severe than other causes. The treatment options available vary including intravenous (IV) insulin, heparin, plasma exchange, fibrates, niacin, omega three fatty acids and dietary restrictions. This is a case report of a patient presenting with HTAP and the dilemma treating physicians faced in trying to balance the need for urgent treatment with invasiveness of procedure and paucity of evidence.

A comprehensive framework for early-onset colorectal cancer research.

Sporadic colorectal cancer has traditionally been viewed as a malignancy of older individuals. However, as the global prevalence of the disease diagnosed in younger individuals (<50 years) is expected to increase within the next decade, greater recognition is now being given to early-onset colorectal cancer. The cause of the predicted rise in prevalence is largely unknown and probably multifactorial. In this Series paper, we discuss the potential underlying causes of early-onset colorectal cancer, the role of energy balance, biological and genomic mechanisms (including microbiome aspects), and the treatment of early-onset colorectal cancer. We have specifically considered the psychosocial challenges of being diagnosed with colorectal cancer at younger age and the potential financial toxicity that might ensue. This Series paper brings a comprehensive review based on the existing data in the hopes of optimising the overall outcomes for patients with early-onset colorectal cancer.

Electrochemical Quantification of Tobramycin Retention in Pseudomonas aeruginosa as Antimicrobial Susceptibility Indicator.

The emergence and spread of bacterial resistance to antibiotics has developed into one of the most challenging threats to public health. Antibiotic susceptibility tests (ASTs) for bacterial infections are now essential, because they provide guidance for physicians in the selection of antibiotics, to which bacteria will respond. Most current AST methods require long periods of time, because of bacterial growth and incubation, leading to a prolonged and overuse of broad-spectrum antibiotics. Thus, there is a growing demand for methods and technologies that enable rapid antibiotic susceptibility assessment. Due to advantages related to cost-effectiveness, rapid response time and high sensitivity, electrochemical detection methods are promising analytical tools that can successfully quantify antibiotic uptake and retention in clinically relevant bacterial strains. This study presents the electroanalytical quantification of tobramycin (TOB) retention in susceptible and resistant bacterial strains of Pseudomonas aeruginosa. The electrochemical behavior of TOB was characterized by voltammetry, identifying redox potentials, the current dependence on pH conditions, and the detection limit at unmodified glassy carbon electrodes. The presented methodology was able to distinguish between susceptible and resistant bacterial strains, and is also capable of identifying varying degrees of resistance against TOB. The presented approach detects the immediate interaction of bacteria with an antibiotic, without the need of complex and cost-intense equipment related to genomic testing methods.

New insights in improving sustainability in meat production: opportunities and challenges.

Treating livestock as senseless production machines has led to rampant depletion of natural resources, enhanced greenhouse gas emissions, gross animal welfare violations, and other ethical issues. It has essentially instigated constant scrutiny of conventional meat production by various experts and scientists. Sustainably in the meat sector is a big challenge which requires a multifaced and holistic approach. Novel tools like digitalization of the farming system and livestock market, precision livestock farming, application of remote sensing and artificial intelligence to manage production and environmental impact/GHG emission, can help in attaining sustainability in this sector. Further, improving nutrient use efficiency and recycling in feed and animal production through integration with agroecology and industrial ecology, improving individual animal and herd health by ensuring proper biosecurity measures and selective breeding, and welfare by mitigating animal stress during production are also key elements in achieving sustainability in meat production. In addition, sustainability bears a direct relationship with various social dimensions of meat production efficiency such as non-market attributes, balance between demand and consumption, market and policy failures. The present review critically examines the various aspects that significantly impact the efficiency and sustainability of meat production.

Predicting outcomes of mesenteric ischemia postcardiac surgery: A systematic review.

OBJECTIVE: This systematic review aims to identify predictors of outcomes of mesenteric ischemia in patients following cardiac surgery. METHODS: A comprehensive literature search was done on EMBASE, PubMed, Ovid MEDLINE, and SCOPUS using keywords relating to bowel ischemia and cardiac surgery. Database search results were screened by at least two authors and 32 articles were selected for inclusion in this review. RESULTS: Data on 1907 patients were analyzed. The mean age was 70.0 ± 2.99 years and the prevalence of bowel ischemia was 1.74%. Advanced age was a significant risk factor. 63.16% of patients reported were men, and 58.4% of patients died in hospital. There was heterogeneity in the reported significance of the following preoperative risk factors: hypertension, smoking status, type 2 diabetes mellitus, end-stage renal disease, preoperative left ventricular ejection fraction <35%. Cardiopulmonary bypass (CPB) time, preoperative/operative intra-aortic balloon pump (IABP) support, and inotrope usage were significantly associated with the development of mesenteric ischemia; however, other intraoperative factors including the type of cardiac surgery and duration of aortic cross-clamping had varying levels of reported significance. There were discrepancies in the reported significance of leukocytosis and metabolic acidosis (pH <7.3) as postoperative markers. Postoperative vasopressor use, prolonged ventilation time, and elevation in lactate, transaminases, creatinine, and intestinal fatty acid-binding protein (IFABP) levels were found to be strongly associated with bowel ischemia. CONCLUSION: This systematic review found the strongest associations of mesenteric ischemia postcardiac surgery to be advanced age, CPB time, rise in lactate, transaminases, creatinine, and IFABP. IABP support, vasopressor, and inotrope use as well as prolonged ventilation were strongly linked too.

Implementation of an Intelligent Exam Supervision System Using Deep Learning Algorithms.

Examination cheating activities like whispering, head movements, hand movements, or hand contact are extensively involved, and the rectitude and worthiness of fair and unbiased examination are prohibited by such cheating activities. The aim of this research is to develop a model to supervise or control unethical activities in real-time examinations. Exam supervision is fallible due to limited human abilities and capacity to handle students in examination centers, and these errors can be reduced with the help of the Automatic Invigilation System. This work presents an automated system for exams invigilation using deep learning approaches i.e., Faster Regional Convolution Neural Network (RCNN). Faster RCNN is an object detection algorithm that is implemented to detect the suspicious activities of students during examinations based on their head movements, and for student identification, MTCNN (Multi-task Cascaded Convolutional Neural Networks) is used for face detection and recognition. The training accuracy of the proposed model is 99.5% and the testing accuracy is 98.5%. The model is fully efficient in detecting and monitoring more than 100 students in one frame during examinations. Different real-time scenarios are considered to evaluate the performance of the Automatic Invigilation System. The proposed invigilation model can be implemented in colleges, universities, and schools to detect and monitor student suspicious activities. Hopefully, through the implementation of the proposed invigilation system, we can prevent and solve the problem of cheating because it is unethical.

Comparative genomics with evolutionary lineage in Streptomyces bacteria reveals high biosynthetic potentials.

Genome mining in silico approaches allow scientists to proficiently evaluate the genomic potency of secondary bioactive chemical producers and find new bioactive compounds in different bacteria. Streptomyces is one of the most ubiquitous bacterial genera in the environments, and well-known as prolific producers of diverse and valuable natural products (NPs) with significant biological activities. Mining and prioritizing of NP biosynthetic gene clusters (BGCs) would be the most important stage in the identification of novel compounds. Comparative genomics and genetic similarity network analysis of 62 Streptomyces public reference genomes demonstrated that individuals of these species exhibit a huge number of distinct NP BGCs, the most of which are cryptic and unconnected to any reported NPs with high phylogenetic variation among individuals. It was assumed that substantial heterogeneity across the varieties of species of Streptomyces drives outstanding biosynthetic and metabolic potential, making them plausible candidates for the identification of novel molecules.

Phytochemical, enzymatic and biological studies of root extracts of Farsetia hamiltonii Royle.

Farsetia hamiltonii Royle is a medicinal plant of Cholistan desert, Pakistan, traditionally used for treating diabetes, oxidative stress, arthritis, fever, gastrointestinal and respiratory diseases. This study represents unprecedented phytochemical, enzymatic and biological properties of F. hamiltonii root extracts to prove floric uses. Evaluation of Phytochemical constituents was done by screening, total flavonoid, phenolic contents and gas chromatography-mass spectrometry. The phytochemical screening revealed the presence of glycosides, bounded anthraquinones, flavonoids, saponins, steroids, coumarins and diterpenes in root extracts. Eight compounds were identified in dichloromethane extract, whereas one compound was identified in methanol extract of root part of F. hamiltonii. The dichloromethane extract possesses significant lipoxygenase, chymotripsin and cholinesterase enzyme inhibition activities, whereas methanol extract possess lipoxygenase, alpha glucosidase, chymotrypsin and acetylcholinesterase enzyme inhibition activities. The antibacterial activity of methanol extract was significant against selected five microbial strains. Nine compounds were reported in root part of F. hamiltonii first time. The enzyme inhibition assays on anti-cholinesterase, anti-alpha glucosidase, antilipoxygenase, antichymotripsin and antibacterial activities were found significant for the extracts of root parts of F. hamiltonii. Therefore, results of this study justify folkloric therapeutic potential of F. hamiltonii root in treating diabetes, inflammations and infectious diseases.

The Role of Immunotherapy in Hepatocellular Carcinoma: A Systematic Review and Pooled Analysis of 2,402 Patients.

BACKGROUND: Immune checkpoints inhibitors (ICIs) have emerged as a treatment option for several malignancies. Nivolumab, pembrolizumab, nivolumab plus ipilimumab, and atezolizumab plus bevacizumab have been approved for the management of advanced-stage hepatocellular carcinoma (HCC). We aimed to systematically review the literature and summarize the characteristics and outcomes of patients with HCC treated with ICIs. METHODS: A systematic literature search of PubMed, the Cochrane Library, and ClinicalTrials.gov was performed according to the PRISMA statement (end of search date: November 7, 2020). Quality of evidence assessment was also performed. RESULTS: Sixty-three articles including 2,402 patients were analyzed, 2,376 of whom received ICIs for unresectable HCC. Response to ICIs could be evaluated in 2,116 patients; the overall objective response rate (ORR) and disease control rate (DCR) were 22.7% and 60.7%, respectively, and the mean overall survival (OS) was 15.8 months. The ORR, DCR, and OS for nivolumab (n = 846) were 19.7%, 51.1%, and 18.7 months, respectively; for pembrolizumab (n = 435) they were 20.7%, 64.6% and 13.3 months, respectively. The combination of atezolizumab/bevacizumab (n = 460) demonstrated an ORR and DCR of 30% and 77%, respectively. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence); fatal graft rejection was reported in 40.0% (n = 6/15) and mortality in 80.0% (n = 12/15). CONCLUSION: ICIs are safe and effective against unresectable HCC, but caution is warranted regarding their use in the LT setting because of the high graft rejection rate. IMPLICATIONS FOR PRACTICE: This systematic review pooled the outcomes from studies reporting on the use of immune checkpoint inhibitors (ICIs) for the management of 2,402 patients with advanced-stage hepatocellular carcinoma (HCC), 2,376 of whom had unresectable HCC. The objective response rate and disease control rate were 22.7% and 60.7%, respectively, and the mean overall survival was 15.8 months. The overall rate of treatment discontinuation because of adverse events was 14.9%. Fifteen patients received ICIs in the liver transplant (LT) setting (one pre-LT for bridging, 14 for post-LT recurrence). Six of these patients experienced graft rejection (40.0%).

Medical Procedure Services in Internal Medicine Residencies in the US: a Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: The number of procedures performed by internal medicine residents in the United States (US) is declining. An increasing proportion of residents do not feel confident performing essential invasive bedside procedures and, upon graduation, desire additional training. Several residency programs have utilized the medical procedure service (MPS) to address this issue. We aim to summarize the current state of evidence by systematically evaluating the effect of the MPS on resident education, comfort, and training, as well as patient safety and procedural outcomes in the US. METHODS: We conducted a systematic review of all studies reporting the use of an MPS with supervision from a board-certified physician in internal medicine residencies in the US. Database search was performed on PubMed, Embase, ERIC, and Cochrane Library from January 2000 to November 2020 for relevant studies. Quality of evidence assessment and random-effects proportion meta-analyses were performed. RESULTS: A total of nine studies reporting on 3879 procedures performed by MPS were identified. Procedures were safely performed, with a pooled complication rate of 2.1% (95% CI: 1.0-3.5) and generally successful, with a pooled success rate of 94.7% (95% CI: 90.8-97.7). The range of procedures performed by residents under MPS was 6.7-72.8 procedures per month (n = 9) compared to 4.3-64.4 procedures (n = 4) without MPS. MPS significantly increased confidence, comfort, and use of appropriate safety measures among residents. CONCLUSION: There are a limited number of published studies on MPS supervised by a board-certified physician in US internal medicine residencies. Procedures performed by MPS are generally successfully completed and safe. MPS benefits internal medicine residents training by improving competency, comfort, and confidence.

Trends in per-operative parameters and postoperative complications associated with coronary artery bypass graft surgery (CABG); A four-year retrospective study.

OBJECTIVE: To determine the patterns of per-operative parameters and early outcomes of patients that underwent CABG surgery during a four-year period. METHODS: This is a cross-sectional descriptive study conducted in a tertiary care of hospital from November 2020 to January 2021. All the patients that underwent the isolated coronary artery bypass grafting (CABG) procedure were included in the study from June 2017 till June 2020. Data was collected on a data extraction form and stored in SPSS format which was analyzed for qualitative statistics keeping p<0.05 as significant. All the results were represented in the form of tables. RESULTS: A total of 1,613 patients were operated upon for Coronary Artery Bypass Grafting (CABG) procedure during the study period with 1,222 (75.8%) males and 391 (24.2%) females. Dyslipidemia (71.8%) was the most common risk factor. The average perfusion time decreased only slightly (~1 minute) from 96.01 minutes to 95.07 minutes (2017 to 2020). This change however was not significant (p=0.301). The rate of Left Internal Mammary Artery (LIMA) use stayed relatively stable over the 4-year period fluctuating between 88.7% and 92.9% (p=0.360). The average initial ICU stay (in hours), drain at 12 hours and 24 hours stays almost the same. The rate of mortality peaked in 2018 (4.76%) and subsequently fell to 3.57% by 2020. CONCLUSION: More males underwent CABG surgery at this tertiary care hospital and the overall complication rate and per-operative parameters improved over the years. The non-risk stratified mortality in this study was found to be higher than developed nations.

SNP of HMGCR and Apo E genes and their impact in response to statin therapy in hypercholesterolemic and hypertriglyceridemic patients in Pakistan.

Coronary artery disease (CAD) and the problems associated with it are the most prominent causes of death in the whole world. Statins are accustomed to lower lipid levels in CAD patients. The target of this study was to analyze whether or not common variations in HMGCoA Reductase (HMGCR) and Apolipoprotein E (ApoE) genes are responsible for metabolism of lipid and statin that modify the impact of statins on serum level of lipids and lipoprotein concentrations in Coronary heart disease patients. One hundred CAD patients were registered for the study. At the start of the study biochemical measurements were performed to work out the baseline levels. Patients were treated with twenty mg Lipitor for one month and biochemical measurements were tested again. According to the post-treatment, LDL-c levels, patients were divided into a pair of group as non-responders and responders, independently. The information concerning the risk factors like smoking, alcohol consumption etc. was conjointly obtained. DNA was extracted from peripheral blood. The presence of rs17244841 and rs17238540 mutations in HMGCR and έ2, έ3 and έ4 variants of ApoE were settled by performing RT-PCR. Results were assessed statistically. HMGCR mutations were principally found in responders and ε4 variant of ApoE was principally found in non-responders. It was found that the presence of HMGCR mutations causes a big reduction in total cholesterol and LDL-c levels. Conjointly, the presence of έ2 variant of Apo E causes a statistically vital increase in triglyceride levels. Our findings should be investigated by different researchers to clarify the mechanism.

The changes of inflammatory mediators and vasoactive substances in dairy cows' plasma with pasture-associated laminitis.

BACKGROUND: Hoof disease is one of the three major diseases that often occur in dairy cows. The impact of this disease on dairy farming is second only to mastitis. Laminitis is a diffuse, aseptic, serous, non-purulent inflammation of the dermal papillae and vascular layers of the cow's hoof wall. In the pasture, laminitis occurs mostly in the laminae, that is, inside the hoof shell. No lesions can be seen on the surface. Therefore, laminitis cannot attract the attention of veterinarians. However, laminitis has become a major factor that seriously affects the health and welfare of dairy cows, making it an important cause of hindering the performance of dairy cows. METHODS: The study was conducted at a dairy farm in Harbin, Heilongjiang province, China. We selected a sample of the laminitis cows based on the veterinary diagnosis, took blood from the jugular vein and then separated the plasma, and measured the index with the Elisa kit. In this study, the markers of inflammatory and vasoactive substances status in dairy cows consisted of subclinical laminitis (SCL, n = 20), chronic laminitis (CL, n = 20) and healthy dairy cows (CON, n = 20) under the local management conditions were investigated. RESULTS: Compared with healthy cattle, HIS, IL-6, LPS, and TNF-α in subclinical laminitis group significantly increased (P < 0.05), especially HIS, LPS, TNF-α (P < 0.01); in chronic laminitis cows, COX-2, HIS, IL-6, LPS, and TNF-α increased significantly (P < 0.05), especially COX-2, HIS, TNF-α (P < 0.01). iNOS (P < 0.05), TXB2 (P < 0.01) in chronic laminitis cows had significantly increased. CONCLUSION: This study reported for the first time that pasture laminitis was divided into subclinical laminitis and clinical chronic laminitis. Through research on the inflammatory factors and vasoactive substances of dairy cows, it is found that there is a close relationship between them, which affects the metabolic cycle of dairy cows. These indicators are abnormally expressed and cause hoof microcirculation disorders.

Fungal recovery and characterization from Hindu Kush mountain range, Tirich Mir glacier, and their potential for biotechnological applications.

The Hindu Kush mountains spread over Northern areas of Pakistan having hundreds of glaciers representing a unique ecosystem driven by the specific geochemistry and climate. The current study measured the distribution of culturable fungi in Tirich Mir glacier, Hindu Kush range, and the potential of these isolates to show antimicrobial activity and produce biotechnologically important enzymes. Samples of glacial ice, sediments, and meltwater were collected from Tirich Mir glacier, and 46 fungal strains were isolated and characterized for identity and biotechnological applications. The findings revealed Penicillium (10) as the most common genus, followed by Alternaria (9), Cladosporium (7), Coprinopsis, two isolates each belonging to genus Phoma, Ulocladium, Epicoccum, Onygenales, and Didymella, and one isolate of genus Davidiella, Aspergillus, Geomyces, Dothideomycetes, Pseudogymnoascus, Irpex, Scopulariopsis, Ascochyta, Tomicus, and Davidiellaceae. Davidiella tassiana HTF9 showed growth in the presence of 18% NaCl and pH 2, 3, 5, 7, 9, and 11. The isolates Ulocladium sp. and Onygenales sp. inhibited the growth of test fungi, Gram-negative and positive bacteria. Fungal strains were capable of producing cold-active enzymes, including cellulase, lipase, amylase, and deoxyribonuclease. The isolate Penicillium chrysogenum HTF24 was an efficient producer of amylase, deoxyribonuclease, and cellulase. The fungi of high-altitude glaciers are potent candidates for biotechnological applications; however, studies using more sensitive techniques are needed for further exploration.

Evaluation of diet as a risk factor in the development of childhood leukaemia: a case control study.

OBJECTIVE: To evaluate probable association of dietary risk factors with childhood leukaemia. METHODS: The case-control study was conducted at the Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from January to December 2017, and comprised children of either gender aged 2-12 years with recently diagnosed acute lymphocytic or acute myelocytic leukaemia An age and gender matched equal group of healthy children was taken as controls. Dietary-intake data was collected for six food groups, namely raw vegetables, fresh fruits, packed fruit juices, caffeinated drinks, junk foods, and processed/precooked food items. Frequency of the selected food group consumption was summarised in six categories: rarely/never, 1-3 days/week, 4-6 days/week, once daily, twice daily and thrice daily. Data was collected through interviews with the mothers using a pre-designed questionnaire, and was analysed using SPSS 21. RESULTS: Of the 90 subjects, 45(50%) were in each of the two groups. There were no differences in baseline characteristics between the two groups (p>0.05). Consumption of caffeinated drinks and junk food was significantly higher in cases (p=0.001) while controls showed significantly higher consumption of fresh fruits (p=0.0012). No significant difference was noted for consumption of vegetables, packed fruit juices and processed food between the groups (p> 0. 05 ). CONCLUSIONS: Higher consumption of caffeinated drinks and junk food was observed in cases compared to controls.