Hypophosphatemia and Hyponatremia in Systemic Lupus Erythematosus Patients and Its Relation to Clinical Characteristic and Disease Activity

Background: Systemic Lupus Erythematosus (SLE) is a chronic auto-immune disease with diverse manifestations, ranging from mild rash or arthritis to severe organ-threatening involvement.Objective: The aim of the work was to find-out the possible association of hypophosphatemia and hyponatremia with disease activity in SLE patients.Patients and methods: A total of 100 patients with SLE were involved in this study and the serum level of sodium and phosphorus, erythrocyte sedimentation rate (ESR), leucocytic and platelet counts, and 24 hr. protein were measured. SLE disease activity index (SLEDAI) score was assessed,Results: The majority of patients were females; 94 (94%) and 6 males (6%) (F:M 15.7:1). The age of the patient ranged from 17 to 63 years with a mean age of 34.23 ±11.19 years. The disease duration was 48±55.7 months. 7. 41% of SLE patients were hyponatremic and 49% showed normonatremic. There was a significant correlation between Na level, SLEDAI score, vasculitis and arthritis and insignificant correlation with ESR. 47 patients were hypophosphatemic  (47%) and 53 (53%) were normophophatemic. There was a significant correlation between phosphate level and SLEDAI, oral ulcers p=0.001 and arthritis p<0.0004 but negatively related with ESR.Conclusion: It could be concluded that hyponatremia and hypophosphatemia are significantly related to SLEDAI, so it could be used as indicators of SLE activity and sever inflammation

Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

Liver fibrosis is a common chronic hepatic disease. This study aimed to investigate the effect of pitavastatin (Pit) against thioacetamide (TAA)-induced liver fibrosis. Rats were divided into four groups: (1) control group; (2) TAA group (100 mg/kg, i.p.) three times weekly for 2 weeks; (3 and 4) TAA/Pit-treated group, in which Pit was administered orally (0.4 and 0.8 mg/kg/day) for 2 weeks following TAA injections. TAA caused liver damage manifested by elevated serum transaminases, reduced albumin and histological alterations. Hepatic malondialdehyde (MDA) was increased, and glutathione (GSH) and superoxide dismutase (SOD) were decreased in TAA-administered rats. TAA upregulated the inflammatory markers NF-κB, NF-κB p65, TNF-α and IL-6. Treatment with Pit ameliorated serum transaminases, elevated serum albumin and prevented histopathological changes in TAA-intoxicated rats. Pit suppressed MDA, NF-κB, NF-κB p65, the inflammatory cytokines and PI3K mRNA in TAA-intoxicated rats. In addition, Pit enhanced hepatic antioxidants and boosted the nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA. Moreover, immunohistological studies supported the ability of Pit to reduce liver fibrosis via suppressing p-AKT expression. In conclusion, Pit effectively prevents TAA-induced liver fibrosis by attenuating oxidative stress and the inflammatory response. The hepatoprotective efficacy of Pit was associated with the upregulation of Nrf2/HO-1 and downregulation of NF-κB and PI3K/Akt signalling pathways

Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway

This research investigated if pitavastatin (Pita) might protect rats' kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, p-Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health

Vitamin D Status in Neonatal Pulmonary Infections: Relationship to Inflammatory Indicators

AIM: The study aimed to evaluate serum vitamin D concentrations among neonates with pneumonia. METHODS: This case-control study enrolled 33 neonates with pneumonia in addition to 30 healthy controls. CBC, CRP, Serum vitamin D and Pentraxin 3 levels were measured for all participants. RESULTS: There was significant difference between patients and controls regarding Hemoglobin levels, TLC and CRP (p value < 0.01, = 0.002, < 0.01 respectively). Patients with pneumonia showed significant lower levels of Vit. D (9 ± 2.1) compared to controls (14.1 ± 2.8), P value < 0.01. However, patient group had significant higher levels of Pentraxin 3 (29.1 ± 4.8) compared with controls (12.6 ± 3), P value < 0.01. Moreover, mechanically ventilated patients revealed significant lower vit D (7.7 ± 1.8) and higher pentraxin 3 (32.2 ± 2.6) compared to patients on free oxygen (9.1 ± 2.1, 26.4 ± 3.7 respectively), P value = 0.05, 0.02 respectively. Regarding hospital stay, it had significant positive correlation with serum pentraxin 3 (r = 0.6, P value < 0.01) and significant negative correlation with serum vit D (r = -0.4, P value = 0.04). Finally a significant negative correlation between serum levels of vitamin D and Pentraxin 3 was found (r = -0.4, P value = 0.01). CONCLUSION: Lower concentration of serum vitamin D may be significantly associated with neonatal pneumonia. It also can predict the need for mechanical ventilation and duration of hospital stay in neonatal pneumonia. Similarly, higher levels of Pentraxin 3 may be used as an indicator for mechanical ventilation need and a longer hospital stay in neonates with pneumonia

The Malaysia DREEM: perceptions of medical students about the learning environment in a medical school in Malaysia

BACKGROUND: Students’ perceptions of their learning environment, by defining its strengths and weaknesses, are important for continuous improvement of the educational environments and curriculum. Therefore, the aim of this study was to explore students’ perceptions of their learning environment, among medical students in Malaysia. Various aspects of the education environment were compared between year levels and sex. METHODS: This cross-sectional study was conducted at the Management and Science University, Shah Alam, Malaysia in 2012. A total number of 438 medical students participated in this study, and the response rate was 87.6%. Data were analyzed using SPSS. Comparisons of the mean scores of Dundee Ready Education Environment Measure (DREEM) subscales were calculated. The t-test was used to determine statistically significant differences. RESULTS: The majority of the study participants were female, Malay, and from year 3 (68.7%, 65.3%, and 55.7%; respectively). Analysis of each of the 50 items of the DREEM inventory showed that 47 items scored ranged between 2.00 and 3.00, and three items scored below 2.00. These were identified as problem areas in this medical school that are required to be critically addressed. The overall score showed that the medical students’ perceptions were positive. The students’ perception toward educational environment was positive for all five DREEM subscales. CONCLUSION: The study found that, in general, the perceptions of the participants about the learning environment were positive. Nevertheless, the study also found there is a need for curriculum improvement in this school and identified priority areas for such improvement

Core Microbial Functional Activities in Ocean Environments Revealed by Global Metagenomic Profiling Analyses

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.This work was supported by King Abdullah University for Science and Technology Global Collaborative Partners (GCR) program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

<p>Abstract</p> <p>Background</p> <p>Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.</p> <p>We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.</p> <p>Results</p> <p>A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.</p> <p>Conclusions</p> <p>Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.</p

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication