Impacts of Work Environment on Health Status of Traffic Compliance and Enforcement Corps Members in Ogun State. Nigeria

Background: Traffic Compliance and Enforcement (TRACE) Corps members in Nigeria are occupationally exposed to lots of environmental pollutants due to essential services that they render in the transport industry. Exposure to environmental pollutants has been shown to contribute to the pathogenesis and progression of cardiovascular diseases (CVD). Information about biochemical end points of CVD in Traffic Compliance and Enforcement (TRACE) Corps members who are occupationally exposed to environmental pollutants is lacking. This study therefore investigated the effects of these environmental pollutants on some indices of CVD. Methods: Before enrollment in the study, all subjects, including controls, were informed about the objectives and requirements of the study, as well as the risks and discomfort that might be involved in participating in the study. After this exercise, a total of 234 subjects consented to participate in the study. TRACE (n=195) in various zones in Ogun State. Staff and students at Federal University of Agriculture, Abeokuta (FUNAAB) served as control subjects (n=39). A careful history of their dietary habits and job experience, as well as a detailed history of their occupational habit, was taken. Anthropometric and clinical parameters were assessed using standard methods while biochemical indices of CVD were determined spectrophotometrically using commercial diagnostic kits. One-way analysis of variance (ANOVA) followed by Duncan test was used to analyze the results with p\u3c0.05 considered significant. The relationships between plasma lipids and the anthropometric parameters were also analyzed using Pearson correlations. Results: Results showed that the systolic blood pressure in both male and female TRACE subjects were significantly higher than the control subjects. The diastolic blood pressure remained the same in both the control and TRACE subjects. The pulse in the TRACE male subject was significantly lower than the control subject. The body mass index (BMI), waist circumference and hip circumference of the TRACE female were significantly higher than the control subjects. The umbilical cord circumference of the TRACE male and female subjects were significantly higher than their control counterpart. Plasma Cholesterol in TRACE male was higher than the control male while the plasma cholesterol was lower in TRACE female compared to the control female. Plasma triacylglycerol and phospholipid remain the same in all subjects. HDL cholesterol in the TRACE subjects were 65% and 71% of the control male and control female respectively. Plasma arylesterase in TRACE male and female subjects were both 1.39 times lower than their control counterparts. There was also a significant positive correlation between the plasma cholesterol and weight (r = 0.130; p = 0.047), plasma cholesterol and BMI (r = 0.157; p = 0.021), Plasma triacylglycerol and Pulse (r = 0.130; p = 0.048). The average traffic density was 37 vehicles/min in the sampled TRACE zones. Conclusion: Findings such as increase in systolic blood pressure, anthropometric parameters and lower HDL cholesterol, plasma arylesterase in the TRACE subjects compared to the control from this study indicates that environmental pollutant exposure may disrupt lipid homeostasis and predisposes the TRACE subjects to development of CVD

Beneficial effects of omega-3 fatty acid on dyslipidemia in organs of alloxan-induced diabetic rats

Diabetes Mellitus is one of the heterogeneous metabolic disorders associated with dyslipidemia, a major risk factor contributing to cardiovascular disease. This metabolic abnormality affects virtually all organs. Over the years, antidiabetic drugs which majorly aim at the hyperglycemic aspect of the disease have been used. Therefore, to address this dyslipidemia, omega-3 fatty acid (O3FA) supplement was employed. Its effects on lipid metabolism in the organs (heart, liver, kidney, pancreas, spleen and brain) of alloxan-induced (150mg/kg body weight, intraperitoneally) diabetic male rats were investigated. O3FA (0.4g/kg b.wt/day) was administered as pre- and posttreatment for 2 weeks. The lipid levels were significantly increased (p<0.05) in diabetic rats. O3FA administration significantly reduced (p<0.05) the levels of cholesterol, phospholipids, triacylglycerol by varying extents, in the examined organs without affecting hyperglycemia in the diabetic rats. The ratio of HMG CoA/mevalonate decreased in the liver of the diabetic rats by 28% indicating increased activity of HMG-CoA reductase. This diabetes-induced dyslipidemia was accompanied by a 28% increase in the activity of hepatic HMG-CoA reductase. Administration of O3FA to the diabetic rats however resulted in 10% and 17% decrease in the activity of this enzyme in the pre- and post-treated groups respectively. Also, lipid peroxidation was significantly reduced (p<0.05) by O3FA suggesting that it has protective effect against oxidative damage. This study reveals that O3FAsupplement has beneficial effects in attenuating dyslipidemia observed in diabetes mellitus and could be beneficial as an adjunct in the management of diabetes mellitus

Kinase inhibitor pulldown assay identifies a chemotherapy response signature in triple-negative breast cancer based on purine-binding proteins

UNLABELLED: Triple-negative breast cancer (TNBC) constitutes 10%-15% of all breast tumors. The current standard of care is multiagent chemotherapy, which is effective in only a subset of patients. The original objective of this study was to deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify kinases elevated in non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC before docetaxel- and carboplatin-based neoadjuvant chemotherapy. KIPA was applied to the native tumor lysates that were extracted from samples with high tumor content. Seven percent of all identified proteins were kinases, and none were significantly associated with lack of pCR. However, among a large population of off-target purine-binding proteins (PBP) identified, seven were enriched in pCR-associated samples ( SIGNIFICANCE: The identification of pretreatment predictive biomarkers for pCR in response to neoadjuvant chemotherapy would advance precision treatment for TNBC. To complement standard proteogenomic discovery profiling, a KIPA was deployed and unexpectedly identified a seven-member non-kinase PBP pCR-associated signature. Individual members served diverse pathways including IFN gamma response, nuclear import of DNA repair proteins, and cell death

Surgical site infection after gastrointestinal surgery in children: An international, multicentre, prospective cohort study

IntroductionSurgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda

Genomic complexity predicts resistance to endocrine therapy and CDK4/6 inhibition in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance. EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy-number burden (bCNB). RESULTS: High bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared with patients with low bTMB or low bCNB (all P \u3c 0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) versus low bTMB (0/37, 0%; P = 0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P = 0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R = 0.98). During serial monitoring, an increase in bCNB score preceded radiographic progression in 12 of 18 (66.7%) patients. CONCLUSIONS: Genomic complexity detected by noninvasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population

Global access to technologies to support safe and effective inguinal hernia surgery:prospective, international cohort study

Technological advancement is important to improve healthcare quality and safety, especially in surgery1. For patients with an inguinal hernia, mesh and minimally invasive surgery are the two main technologies that have improved healthcare quality and safety2,3. The use of mesh is proven to reduce recurrence4,5. This avoids the need for further repairs, which are technically more challenging and have a higher risk for patients6. The use of minimally invasive surgery has proven advantages in bilateral hernias and in female patients2,3 and is recommended in unilateral repair where appropriate expertise is available2,3.Access to these technologies and the expertise required are not widely or equitably distributed at a global level. As it is the case for other technologies, countries in the Global South have more limited access1. At the same time, in this part of the globe, there is a higher prevalence and a higher burden of disease associated with inguinal hernias7. Several barriers to implementation in the Global South have been identified previously, including costs, distribution, and training8,9. To overcome these, studies reporting the use of mesh based on mosquito net mesh and evaluating training programmes have been conducted10,11. With these efforts and with global investment in new technologies and the expansion of existing technologies, it was expected that there would be an increase in their use in low–middle-income countries. Data assessing this variability have not been collected in a standardized way and are usually reported from single-country or single-region studies5,12. Therefore, identification of areas where improvement is most needed will be key to better inform policymakers.The overarching aim of this study was to evaluate access to technologies that are relevant to the treatment of inguinal hernia patients to identify the areas where improvement is needed. Therefore, the primary aim of this study was to evaluate the use of mesh and predictors of mesh use in elective inguinal hernia repairs and the secondary aims of this study were to evaluate the use of minimally invasive surgery and predictors of minimally invasive surgery use and to evaluate the safety associated with the use of mesh and the use of minimally invasive surgery

Parity and breastfeeding are protective against breast cancer in Nigerian women

As the relation between reproductive factors and breast cancer risk has not been systematically studied in indigenous women of sub-Saharan Africa, we examined this in a case–control study in Nigeria. In-person interviews were conducted using structured questionnaires to collect detailed reproductive history in 819 breast cancer cases and 569 community controls between 1998 and 2006. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with menarcheal age <17 years, the adjusted OR for women with menarcheal age ⩾17 years was 0.72 (95% CI: 0.54–0.95, P=0.02). Parity was negatively associated with risk (P-trend=0.02) but age at first live birth was not significant (P=0.16). Importantly, breast cancer risk decreased by 7% for every 12 months of breastfeeding (P-trend=0.005). It is worth noting that the distribution of reproductive risk factors changed significantly from early to late birth cohorts in the direction of increasing breast cancer incidence. Our findings also highlight the heterogeneity of breast cancer aetiology across populations, and indicate the need for further studies among indigenous sub-Saharan women

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