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The present study is the first record of deducing age-wise and sex-wise normal reference intervals (RIs) for various serum biochemical attributes in apparently healthy Sipli sheep being reared under intensive farming system at Livestock Farm of the Faculty of Veterinary and Animal Sciences (FV&AS), The Islamia University of Bahawalpur (IUB). Blood samples were aseptically collected, serum was harvested and analyzed for serum chemistry analytes through semiautomatic chemistry analyzer using commercial kits. For the sake of analysis, groups were assigned as per age i.e. G1= up till 1year (n= 41), G2= from 1 to 2 years (n= 46), G3= from 2 to 3 years (n= 43) and as per sex i.e. females (n= 79) and males (n= 51). All the overall mean values and RIs for all the studied attributes were within the reference ranges provided in earlier studies for sheep. Bilirubin, Alkaline Phosphatase (ALP) and creatinine were significantly (P=0.05) lower in females as compared to those in males. However, uric acid was significantly (P=0.05) higher for females 52.8±2.6mmols/L as compared to 44.5±2.9mmols/L for males. The remaining attributes (Alanine Transaminase, Aspartate Aminotransferase, Total Proteins, Albumin, Glucose, Low Density Lipoproteins, High Density Lipoproteins and Urea) did not differ -significantly (P=0.05) between male and female sheep under study. For age-related results, only ALP, glucose and HDL were significantly (P=0.05) different between the three studied age groups of Sipli sheep. The ALP and glucose were higher in G1 animals (up till 1 year) whereas HDL was lower in G2 animals (from 1 to 2 years) as compared to their counter-part groups 1 and 3. The data can be beneficial in diagnostic/prognostic purpose for veterinarians, academicians, researchers and all other stakeholders of sheep-rearing sector in Pakistan as well as for other indigenous sheep breeds being reared under similar climatic conditions throughout the world. [ABSTRACT FROM AUTHOR]

In present findings, a simple pyrolysis technique was applied to decorate S and N doped graphene with RuS2-CoO nanoparticles synthesizing a heterostructured nanocomposite RuS2-CoO@SNG. XPS results demonstrate the elemental composition of these nanomaterials with the hint of metal-metal charge transfer phenomenon likely due to heterostructure composition. These modifications led to a significant active surface area resulting in elevated electrocatalytic performance. In comparison to benchmark Pt/C at -60 mV in 1 M KOH, hydrogen evolution reaction (HER) reached at current density around 10 mA cm-2 at -90 mV overpotential. The stability test displayed excellent results with a decrease of 2 mV in overpotential at current density of 10 mA cm-2. Results indicate that such heterostructured nanocomposites can be used as an effective catalyst for HER., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Naseeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The purpose of this study was to evaluate and compare the values of hexagonality of endothelial cells among type-2 diabetics and nondiabetics. It also aimed at finding the correlation of the hexagonality of endothelial cells with the duration of diabetes, random blood sugar level, and severity of diabetic retinopathy in type-2 diabetics., Materials and Methods: A comparative cross-sectional study was conducted for 8 months from January to August 2022. The data was collected from tertiary care eye hospital named Al-Shifa Trust Eye hospital jhelum road, Rawalpindi, Pakistan. After taking the informed consent, a complete history of each subject was taken. Visual acuity and refraction were performed using Early Treatment Diabetic Retinopathy Study visual acuity chart and then, complete slit-lamp anterior and posterior segment examination was performed followed by specular microscopy (TOMEY Specular Microscope EM-4000) to evaluate endothelial cell hexagonality. The diabetic subjects were checked for their random blood sugar levels immediately after specular microscopy using a digital glucometer and the readings were recorded., Results: Results showed that the hexagonality of endothelial cells was statistically significantly lower ( P = 0.000) in type-2 diabetics than in nondiabetics. Correlation analysis of the hexagonality of endothelial cells showed a negative correlation ( P < 0.05) with random blood sugar levels while no correlation ( P > 0.05) with the duration of diabetes and severity of diabetic retinopathy., Conclusion: The study concluded that the hexagonality of endothelial cells was significantly different among the two groups under study, i.e., type-2 diabetics and nondiabetics., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Oman Ophthalmic Society.)

Perianal Paget's disease (PPD) is a rare skin adenocarcinoma that arises in the apocrine glands of the perianal region. It is often misdiagnosed as eczema, leukoplakia, squamous cell carcinoma, Bowen's disease, lichen planus, or condylomata acuminata. We report a case of a 63-year-old male who presented to the emergency room (ER) for evaluation of an anal mass that had persisted over 6 months. The patient was found to have a rectal adenocarcinoma with pagetoid spread and underwent neoadjuvant chemoradiation with symptom improvement. However, the patient declined further chemotherapy and the planned abdominal perineal resection with reconstruction, as it would require a permanent colostomy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Lefika Bathobakae et al.)

Calcineurin (CN), the only Ca2+/calmodulin-activated protein phosphatase and target of immunosuppressant drugs, dephosphorylates substrates within membrane-associated Ca2+ microdomains. CN binds to substrates and regulators via short linear motifs (SLIMs), PxIxIT and LxVP, which have distinct docking sites on CN. PxIxIT binding to CN is Ca2+-independent and affects its distribution, while LxVP associates only with the active enzyme and promotes catalysis. 31 human proteins contain one or more composite LxVPxIxIT motifs, whose functional properties have not been examined. Here we study calcimembrin/C16orf74 (CLMB), a largely uncharacterized intrinsically disordered protein that contains a composite motif which binds to and directs CN to membranes. CLMB overexpression is associated with poor prognoses for several cancers, suggesting that it promotes oncogenesis by shaping CN signaling. We demonstrate that CLMB associates with membranes via N-myristoylation and dynamic S-acylation and is dephosphorylated by CN on threonine 44 (Thr44). The LxVP and PxIxIT portions of the CLMB composite sequence, together with Thr44 phosphorylation, confer high affinity PxIxIT-mediated binding to CN (KD~8.3 nM) via an extended 33LxVPxIxITxx(p)T44 sequence. This binding promotes CLMB-based targeting of CN to membranes, but also protects Thr44 from dephosphorylation. Thus, we propose that CLMB promotes dephosphorylation in multimeric complexes, where one CLMB molecule recruits CN to membranes via PxIxIT binding, allowing other proteins (including CLMB) to engage through their LxVP motifs for dephosphorylation. This unique mechanism makes dephosphorylation sensitive to CLMB:CN ratios and is supported by in vivo and in vitro data including nuclear magnetic resonance (NMR) analyses of CLMB alone and complexed with CN.

Objectives: To determine the significance of serum arginase estimation as a predictor of pregnancy-induced hypertension and preeclampsia at an early stage., Methods: The observational, cross-sectional study was conducted from October 15, 2021, to October 15, 2022, at the Department of Chemical Pathology, in collaboration with the Department of Obstetrics and Gynaecology, Pakistan Railway Hospital, Islamic International Medical College Trust, Rawalpindi, Pakistan, and comprised pregnant women with 20-25 weeks of gestation who were divided into three groups. Those having no complications were placed in control group A, those with pregnancy-induced hypertension in group B, and those with preeclampsia in group C. Serum arginase, uric acid, alanine transaminase, platelet count and spot urinary protein levels were measured for each subject. Data was analysed using SPSS 26., Results: Of the 90 women, 30(33.3%) were in group A with mean age 27.27±2.90 years, 30(33.3%) were in group B with mean age 30.17±2.48 years, and 30(33.3%) were in group C with mean age 29.33±3.11 years. There were significant intergroup differences in the mean levels of serum arginase, serum uric acid, alanine transaminase, platelet count and spot urinary protein (p<0.05)., Conclusions: A moderate to marked increase in serum arginase levels in pregnancy-induced hypertension and preeclampsia cases, combined with abnormal serum uric acid and alanine transaminase levels along with low platelet count suggested that serum arginase estimation could be used to predict hypertensive disorders of pregnancy at an early stage.

Background: HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes. How, mechanistically, HIF promotes cardiac dysfunction is an open question., Methods: We used mice lacking cardiac pVHL (von Hippel-Lindau protein) to investigate how chronic HIF activation causes multiple features of ischemic cardiomyopathy, such as autophagy induction and lipid accumulation. We performed immunoblot assays, RNA sequencing, mitochondrial and peroxisomal autophagy flux measurements, and live cell imaging on isolated cardiomyocytes. We used CRISPR-Cas9 gene editing in mice to validate a novel mediator of cardiac dysfunction in the setting of chronic HIF activation., Results: We identify a previously unknown pathway by which cardiac HIF activation promotes the loss of mitochondria and peroxisomes. We found that DEPP1 (decidual protein induced by progesterone 1) is induced under hypoxia in a HIF-dependent manner and localizes inside mitochondria. DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes ex vivo. DEPP1 loss increases cardiomyocyte survival in the setting of chronic HIF activation ex vivo, and whole-body Depp1 loss decreases cardiac dysfunction in hearts with chronic HIF activation caused by VHL loss in vivo., Conclusions: Our findings identify DEPP1 as a key component in the cardiac remodeling that occurs with chronic ischemia., Competing Interests: W.G.K. has financial interests in Lilly Pharmaceuticals, Fibrogen, Nextech Invest, Tango Therapeutics, LifeMine Therapeutics, Circle Pharma, IconOVir Bio, and Casdin Capital. The other authors report no conflicts.

Background and Purpose: The purpose of this study is to evaluate the feasibility of using 3-dimensional (3D) ultra-short echo time (UTE) radial imaging method for measurement of the permeability of the blood-brain barrier (BBB) to gadolinium-based contrast agent. In this study, we propose to use the golden-angle radial sparse parallel (GRASP) method with 3D center-out trajectories for UTE, hence named as 3D UTE-GRASP. We first examined the feasibility of using 3D UTE-GRASP dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for differentiating subtle BBB disruptions induced by focused ultrasound (FUS). Then, we examined the BBB permeability changes in Alzheimer's disease (AD) pathology using Alzheimer's disease transgenic mice (5xFAD) at different ages., Methods: For FUS experiments, we used four Sprague Dawley rats at similar ages where we compared BBB permeability of each rat receiving the FUS sonication with different acoustic power (0.4-1.0 MPa). For AD transgenic mice experiments, we included three 5xFAD mice (6, 12, and 16 months old) and three wild-type mice (4, 8, and 12 months old)., Results: The result from FUS experiments showed a progressive increase in BBB permeability with increase of acoustic power (p < .05), demonstrating the sensitivity of DCE-MRI method for detecting subtle changes in BBB disruption. Our AD transgenic mice experiments suggest an early BBB disruption in 5xFAD mice, which is further impaired with aging., Conclusion: The results in this study substantiate the feasibility of using the proposed 3D UTE-GRASP method for detecting subtle BBB permeability changes expected in neurodegenerative diseases, such as AD., (© 2024 American Society of Neuroimaging.)

Objectives: To determine the association of triglyceride-glucose index with homeostasis model assessment of insulin resistance in type 2 diabetes mellitus patients, and to determine the association of triglyceride-glucose index with urinary albumin-to-creatinine ratio for predicting diabetic nephropathy., Methods: The observational, cross-sectional study was conducted from September 2021 to September 2022 at the Department of Chemical Pathology, Pakistan Railway Hospital, Rawalpindi, Pakistan and comprised recently-diagnosed type 2 diabetes mellitus patients. Recorded data included age, gender, vitals, diabetes duration, body mass index and other pertinent demographic and clinical information. Measurements included spot urine albumin-to-creatinine ratio, triglycerideglucose index, homeostasis model assesment of insulin resistance as well as fasting serum insulin, fasting plasma glucose, glycosylated haemoglobin, triglycerides, total cholesterol and serum creatinine. On the basis of triglyceride-glucose index scores, the participants were divided into 4 quartiles; Q1=4.5-5, Q2=5.1-5.5, Q3=5.6-6, and Q4=>6. Data was analysed using SPSS 26., Results: Of the 218 patients, 141(64.7%) were females and 77(35.3%) were males. The overall mean age was 49.22±11.46 years. There were 102(46.8%) overweight patients, 33(15.1%) obese and 82(37.2%) had normal weight. There were 58(26.6%) patients in Q1, 86(39.4%) in Q2, 46(21.1%) in Q3 and 28(12.8%) in Q4. Those in Q4 showed elevated fasting plasma glucose, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and urine albumin-to-creatinine ratio (p<0.05), as well as low values for high-density lipoprotein cholesterol and estimated glomerular filtration rate(p<0.05). Fasting serum insulin was negatively linked to glycated haemoglobin (r=-0.12, p=0.07). Triglyceride-glucose index (r=0.76, p<0.001), homeostasis model assessment of insulin resistance (r=0.48, p<0.001), and urine albumin-to-creatinine ratio (r=0.10,p=0.05) positively correlated with glycated haemoglobin. Fasting serum insulin (r=-0.13, p=0.05), negatively correlated with triglyceride-glucose index, while homeostasis model assessment of insulin resistance (r= 0.32, p<0.001) and urine albumin-to-creatinine ratio (r=0.28, p=0.05) had a positive correlation. The estimated glomerular filtration rate was significantly positively linked with fasting serum insulin (r=0.05, p=0.05), and correlated significantly negatively with triglyceride-glucose index (r=-0.35, p=0.01), homeostasis model assessment of insulin resistance (r=-0.01, p=0.86) and urine albumin-to-creatinine ratio (r=-0.02, p=0.8)., Conclusions: The triglyceride-glucose index showed a strong association with homeostasis model assessment of insulin resistance, and surpassed it in terms of predicting diabetic nephropathy in type 2 diabetes mellitus patients.

Objectives: To explore the behavior patterns of students and working adults regarding the duration and quality of sleep and water intake in an urban environment and to identify the relationship between nighttime sleep extent and water intake with mood and cognitive performance., Methods: This was a descriptive correlational study conducted at Islamic International Medical College, Riphah University at the Pathology department from March to June 2022. A total of 160 participants with age range of 20 to 50 years completed a self-report questionnaire regarding sleep patterns, water intake, and perceptions of mood, concentration, and memory. Analyzed the relationship between sleep duration, water intake, mood, mindfulness/concentration, and memory using Kendall's Tau-b correlation coefficient in SPSS 22., Results: A significant number (28.7%) of participants had a sleep duration of ≤ 6 hours, with 41.3% sleeping after midnight. 82.5% of the participants switch off-screen just before sleeping. 63.7% have a routine water intake of less than 2 L/day. An aberrant statistically significant negative correlation between total sleeping hours and mood (τb = -.313, p = 0.004) was identified, showing a negative effect on mood with a sleeping time of ≥ 9 hours when compared with the other two groups (6-9 hours, τb = - .689, p = 0.001, ≤ 6hours, τb = - .697, p = 0.001). A significant correlation between daily water intake and concentration was found, wherein a decrease in daily water intake showed a negative effect on concentration (τb = .289, p = 0.008)., Conclusions: Sleep duration and water intake patterns may affect mood and cognitive performance. Regular sufficient nighttime sleep and adequate hydration may help improve cognitive functioning and mood., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

The present study is the first of its kind being reported for an indigenous sheep breed of Pakistan with objectives to (a) assess the diagnostic efficacy of a human-based "serum hemolysis reference palette" for sheep serum, (b) deduce normal reference intervals (RIs) for hemoglobin (Hb) and bilirubin, and (c) devise a novel serum color chart for on-field estimation of Hb and bilirubin through color matching of sheep serum. Apparently, healthy Sipli sheep (n = 130) were bled twice attaining whole blood and serum samples (n = 260). The study animals were grouped on the basis of gender, that is, males (n = 51) and females (n = 79) and age, that is, G1 (up till 1 year) (n = 41), G2 (from 1 to 2 years) (n = 46), and G3 (from 2 to 3 years) (n = 43). None of the 260 serum samples of the sheep matched the color given on the human-based "hemolysis reference palette." The G1 animals revealed marked variation in their serum color. Hence, on the basis of RIs, the serum samples (n = 178) of adult sheep (G2 and G3) showing three main color bands were used in devising a novel serum Hb and bilirubin estimation chart for adult sheep serum. In conclusion, the human-based serum hemolysis palette is not valid for sheep serum. The RIs attained in the study could provide a yardstick for assessment of health in indigenous sheep breeds whereas the serum color chart may be of value in estimating Hb and bilirubin in a quick, reliable, and cheaper way for the resource-poor settings of the world., (© 2023 Wiley Periodicals LLC.)

Proper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. Here, we introduce an open-source easy-to-modify multimodal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice, and in anesthetized rats. We show ease of use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate the application of our design for awake functional MRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, using a combined MRI, positron emission tomography and X-ray computed tomography experiment, we demonstrate that our proposed cradle design can be utilized for multiple imaging modalities., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To evaluate and contrast the contrast sensitivity defects present in strabismic and anisometropic amblyopes. And to find out the association of contrast deterioration with the visual acuity of the amblyopic eye, the magnitude of strabismus, and the amount of anisometropia in both groups., Methods: This cross-sectional study was carried out in the orthoptics unit of a tertiary eye care facility between October 2021 and December 2021. There were 45 patients altogether. In the first phase, the patient's history and ocular examination data were recorded after informed consent. The Pelli-Robson chart was used to measure contrast sensitivity. In the second phase, results were interpreted using the SPSS (Statistical Package for the Social Sciences) version 26.0., Results: Strabismic amblyopes were 24 and anisometropic amblyopes were 21. A significant positive association existed between both groups' contrast sensitivity and visual acuity ( P = 0.000). A moderately negative correlation between contrast and anisometropia was statistically significant ( P = 0.025) in anisometropic amblyopes. However, no association ( P > 0.050) existed between the contrast and magnitude of strabismus in any group., Conclusion: The study concluded that contrast sensitivity decreases in both groups, whereas anisometropic amblyopes have poorer contrast than strabismic amblyopes. Excessively decreased contrast sensitivity among anisometropic amblyopes was solely because of the worst amblyopia in this group, whereas the magnitude of strabismus does not affect contrast sensitivity., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Saudi Journal of Ophthalmology.)

We investigated multiple signaling pathways activated by CYP11A1-derived vitamin D3 hydroxymetabolites in human skin fibroblasts by assessing the actions of these molecules on their cognate receptors and by investigating the role of CYP27B1 in their biological activities. The actions of 20(OH)D3, 20,23(OH) 2 D3, 1,20(OH) 2 D3 and 1,20,23(OH) 3 D3 were compared to those of classical 1,25(OH) 2 D3. This was undertaken using wild type (WT) fibroblasts, as well as cells with VDR , RORs , or CYP27B1 genes knocked down with siRNA. Vitamin D3 hydroxymetabolites had an inhibitory effect on the proliferation of WT cells, but this effect was abrogated in cells with silenced VDR or RORs. The collagen expression by WT cells was reduced upon secosteroid treatment. This effect was reversed in cells where VDR or RORs were knocked down where the inhibition of collagen production and the expression of anti-fibrotic genes in response to the hydroxymetabolites was abrogated, along with ablation of their anti-inflammatory action. The knockdown of CYP27B 1 did not change the effect of either 20(OH)D3 or 20,23(OH) 2 D3, indicating that their actions are independent of 1α-hydroxylation. In conclusion, the expression of the VDR and/or RORα/γ receptors in fibroblasts is necessary for the inhibition of both the proliferation and fibrogenic activity of hydroxymetabolites of vitamin D3, while CYP27B1 is not required.

Background: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies., Aim: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches., Methods: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program., Results: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-β in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue., Conclusion: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. Soft tissue plasmacytomas are rare, and a higher burden has been reported in the upper aero-digestive tract, often manifesting as hoarseness, dysphagia, or odynophagia. Due to their rarity, extramedullary plasmacytomas (EMPs) have unknown prognostic factors, and guidelines for optimal management are still lacking. However, radiation therapy and surgery have been used with positive outcomes. Herein, we describe a unique case of plasmacytoma of the pharyngeal tissue in a male patient with a history of HIV disease. The patient completed 28 sessions of radiation therapy, resulting in an improvement in his throat pain and hoarseness. Given the patient's age and lack of traditional risk factors for head and neck cancers, his hoarseness and odynophagia proved to be a diagnostic conundrum. Although infrequent, soft tissue plasmacytomas should be considered in the differential diagnosis of head and neck tumors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cocaine is an indirect-acting sympathomimetic drug that inhibits norepinephrine and dopamine reuptake in the adrenergic presynaptic cleft. Cocaine use has been associated with strokes, angina, arrhythmias, and agitation. Data on gastrointestinal complications such as mesenteric ischemia, bowel necrosis, ulceration, and perforation are scarce. Here, we present a rare case of cocaine-induced esophageal, gastric, and small bowel necrosis that contributes to the limited literature on this subject. Diagnosis of cocaine-induced gastrointestinal complications involves a combination of imaging studies, laboratory assessments, and histopathological examinations. Timely surgical resection, supported by intravenous fluids, antibiotics, and pain management, is the mainstay of treatment. The prognosis varies but is significantly influenced by the promptness and effectiveness of the intervention, underscoring the importance of vigilant clinical care in such cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.