The Role of Organizational Culture in Job Satisfaction and Turnover: A Study of Pakistani Employees

The human capital becomes a significant achievement of every organization in the context of the transformation of the fundamental principles in doing business. Every business structure creates and maintains a unique organizational culture that determines the degree of comfortable conditions for employees in their workplace, the level of their interest in the successful operation of the company and the desire to gain leadership in the market. The human resources and the degree of workers’ satisfaction with jobs directly affect the performance of the company

Effects on egg production and quality of supplementing drinking water with calcium and magnesium

This study was conducted to appraise the effects on egg quality and production performance of laying hens when drinking water was supplemented with calcium (Ca) and magnesium (Mg). A total of 384 (64-week-old) Hy-line Brown laying hens were assigned at random to four treatments, which consisted of CON: unsupplemented drinking water; T1: drinking water + 2 mg/L Ca + 250 mg/L Mg; T2: drinking water + 4 mg/L Ca + 510 mg/L Mg /10 L; and T3: drinking water + 5 mg/L Ca and 760 mg/L Mg. The experiment lasted six weeks. Water intake increased linearly in week 1 with the rising levels of Ca and Mg in the drinking water. Increasing the Ca and Mg levels improved eggshell strength (week 2 (P =0.01), week 5 (P =0.01), and week 6 (P = 0.03), and eggshell thickness (week 6) (P =0.02) and reduced the rate at which eggs were broken (week 4) (P =0.01). The supplemental Ca and Mg did not affect egg production, egg weight, Haugh unit, albumen height, eggshell colour, and yolk colour compared with CON. Nor did they influence the Haugh unit and albumen height after storing for 1, 5, 10 and 15 days. In conclusion, adding Ca and Mg to the drinking water increased the thickness and strength of the eggshells

Palindromic Rheumatism: Biology and Treatment Options

Palindromic rheumatism is a syndrome characterized by recurrent, self-resolving, and inflammatory attacks in and around the joints that have long recognized association with rheumatoid arthritis. PR attacks mostly start in small joints i.e. knees, shoulder, and small joints of the hand. Whether PR should be considered as a single disease or prodrome of RA remains a thought-provoking question. Multiple genetic and environmental factors contribute to the development of PR. Many studies have explained the relationship between a high concentration of Anti-CCP antibodies and PR. Potential benefits of Gold therapy have been recognized in literature but still, there are some questions about toxicity and efficacy that need further considerations. In addition to that anti-malarial drugs, Abatacept, Tofacitinib, and Rituximab showed the variable result in different patients and needed further study to validate their medical use. Moreover, yarrow, oat, colchicum, dill, fennel, wild rue, bitter melon, willow, garlic, and burdock seem suitable candidates to treat rheumatoid although their use in PR is still not reported. Additional experimental researches on these drugs lead to an increase in our knowledge to fight against PR in the future using novel therapeutic approaches. We have attempted to cover this topic in a chapter form to provide a comprehensive view and hope that it will serve as a reference for clinicians who treat patients with PR

Potencial de protección de las semillas Trachyspermum ammi en la nefrotoxicidad inducida por la gentamicina en modelo de conejo

La nefrotoxicidad es uno de los efectos secundarios más importantes limitaciones terapéuticas de los antibióticos aminoglucósidos, especialmente gentamicina. La nefrotoxicidad inducida por gentamicina implica generación de radicales libres, la reducción en el mecanismo de defensa antioxidante y la disfunción renal. Una serie de extractos de hierbas crudas tienen potencial para mejorar la nefrotoxicidad inducida por gentamicina debido a la presencia de varios compuestos antioxidantes. Por lo tanto, el objetivo del presente estudio fue evaluar la actividad protectora del extracto acuoso semillas de T. ammi contra la nefrotoxicidad inducida por gentamicina en conejos albinos. Los resultados mostraron que la gentamicina causó graves alteraciones en los parámetros bioquímicos séricos y los marcadores de riñón, junto con alteraciones severas en los tejidos renales. Sin embargo, el extracto de T. ammi, cuando se administra junto con la gentamicina, invierte la gravedad de la nefrotoxicidad inducida por gentamicina por la normalización de los indicadores de la función renal, por ejemplo, urea sérica, creatinina, nitrógeno ureico en sangre, albúmina y los parámetros de electrolitos séricos que indican el potencial nefroprotector de T. ammi. Del mismo modo, el extracto tiene la capacidad para aumentar la maquinaria enzimática antioxidante endógena mediante un aumento de la actividad de la enzima antioxidante catalasa y reduciendo el estado total de oxidante. El potencial nefroprotector fue confirmado por el examen histopatológico. El potencial nefroprotector podría ser debido a la presencia de compuestos polifenólicos antioxidantes en el extracto acuoso de semillas de T. Ammi

Selected thiadiazine-thione derivatives attenuate neuroinflammation in chronic constriction injury induced neuropathy

Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. In silico molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner

An Unbiased Lipid Phenotyping Approach To Study the Genetic Determinants of Lipids and Their Association with Coronary Heart Disease Risk Factors.

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4-51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

Funder: PfizerFunder: NovartisFunder: National Institute for Health ResearchFunder: MerckBackgroundGenetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.MethodsWe characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.ResultsWe identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.ConclusionsOur findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci

An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4–51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis