Temperature and cardiovascular diseases: exploring associations in India and public health insights

Abstract Background Climate change has far-reaching consequences on human health globally. Cardiovascular diseases (CVDs), the global leading cause of death, are climate sensitive, mainly to temperature. The temperature-CVD association is region-specific, with several studies from Europe but relatively few from low-and-middle-income countries (LMICs). Methods We used a binomial regression model to analyze the association between apparent temperature and in-hospital CVD mortality in Puducherry city. A distributed lag non-linear model was used to capture the delayed and non-linear trends over a 21 day lag period to estimate the burden of in-hospital CVD mortalities attributable to non-optimal temperature between 2010 and 2020. Results Tapp in Puducherry ranges from 23°C to 40°C. We found that the optimal temperature range for Puducherry is between 33°C and 35°C with respect to CVDs. Temperatures both above and below the optimal temperature range were associated with an increased risk of overall in-hospital CVD mortalities, resulting in a U-shaped association curve. Up to 20% of the CVD deaths could be attributable to non-optimal temperatures, with a slightly higher burden attributable to cold (11.2%) than heat (9.12%). We also found that males above 60 years of age were more vulnerable to colder temperatures while females above 60 years were more vulnerable to the heat. Mortality with cerebrovascular accidents was associated more with heat compared to cold, and ischemic heart diseases did not seem to be affected by temperature. Conclusions Both cold and heat is associated with CVD mortality in Puducherry. The comparison of the results of this exploratory Indian study with those from European contexts show that the associations differ based on several factors. There are also age, gender and CVD type differences in Tapp attributable CVD mortalities. More region specific studies on Tapp- CVD mortality are needed from LMICs to better understand this association and build capacity. Key messages • The regional burden of cold attributable CVD deaths needs to be considered along with heat. Age and gender specific differences in the association need to be further studied globally. • The development regional and contextual climate-health action plans, as seen in some European countries, could be enhanced by such studies and reduce the burden of temperature attributable CVD deaths

Contamination of rural surface and ground water by endosulfan in farming areas of the Western Cape, South Africa

BACKGROUND: In South Africa there is little data on environmental pollution of rural water sources by agrochemicals. METHODS: This study investigated pesticide contamination of ground and surface water in three intensive agricultural areas in the Western Cape: the Hex River Valley, Grabouw and Piketberg. Monitoring for endosulfan and chlorpyrifos at low levels was conducted as well as screening for other pesticides. RESULTS: The quantification limit for endosulfan was 0.1 μg/L. Endosulfan was found to be widespread in ground water, surface water and drinking water. The contamination was mostly at low levels, but regularly exceeded the European Drinking Water Standard of 0.1 μg/L. The two most contaminated sites were a sub-surface drain in the Hex River Valley and a dam in Grabouw, with 0.83 ± 1.0 μg/L (n = 21) and 3.16 ± 3.5 μg/L (n = 13) average endosulfan levels respectively. Other pesticides including chlorpyrifos, azinphos-methyl, fenarimol, iprodione, deltamethrin, penconazole and prothiofos were detected. Endosulfan was most frequently detected in Grabouw (69%) followed by Hex River (46%) and Piketberg (39%). Detections were more frequent in surface water (47%) than in groundwater (32%) and coincided with irrigation, and to a lesser extent, to spraying and trigger rains. Total dietary endosulfan intake calculated from levels found in drinking water did not exceed the Joint WHO/FAO Meeting on Pesticide Residues (JMPR) criteria. CONCLUSION: The study has shown the need for monitoring of pesticide contamination in surface and groundwater, and the development of drinking water quality standards for specific pesticides in South Africa

Fetal loss and maternal serum levels of 2,2',4,4',5,5'-hexachlorbiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure: a cohort study in Greenland and two European populations

<p>Abstract</p> <p>Background</p> <p>In the present study, the aim is to examine the risk of fetal loss related to environmental 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) or 1,1-dichloro-2,2-bis(<it>p</it>-chlorophenyl)ethylene (p,p'-DDE) exposure.</p> <p>Methods</p> <p>We related LC/MS/MS measurements of CB-153 and p,p'-DDE in serum samples to interview-data on previous fetal loss in populations of pregnant women from Poland, Ukraine and Greenland.</p> <p>Results</p> <p>In total, 1710 women were interviewed, and 678 of these had at least one previous pregnancy. The risk of ever experiencing a fetal loss increased at higher levels of CB-153 and p,p'-DDE exposure, with an adjusted odds ratio (OR) of 2.4; confidence interval (CI) (1.1-5.5) for CB-153>200 ng/g lipid compared to 0-25 ng CB-153/g lipid and OR of 2.5 CI (0.9-6.6) for p,p'-DDE>1500 ng/g lipid compared to 0-250 ng DDE/g lipid. However, no clear dose response associations were observed. The results further suggest that high level of organochlorine serum concentrations may be related to repeated loss.</p> <p>Conclusions</p> <p>The risk of fetal loss may increase at higher levels of CB-153 and p,p'-DDE exposure, although lack of dose response and inconsistencies between countries did not allow for firm conclusions.</p

Screening of Microorganisms for Biodegradation of Simazine Pollution (Obsolete Pesticide Azotop 50 WP)

The capability of environmental microorganisms to biodegrade simazine—an active substance of 2-chloro-s-triazine herbicides (pesticide waste since 2007)—was assessed. An enormous metabolic potential of microorganisms impels to explore the possibilities of using them as an alternative way for thermal and chemical methods of utilization. First, the biotope rich in microorganisms resistant to simazine was examined. Only the higher dose of simazine (100 mg/l) had an actual influence on quantity of bacteria and environmental fungi incubated on substrate with simazine. Most simazine-resistant bacteria populated activated sludge and biohumus (vermicompost); the biggest strain of resistant fungi was found in floral soil and risosphere soil of maize. Compost and biohumus were the sources of microorganisms which biodegraded simazine, though either of them was the dominant considering the quantity of simazine-resistant microorganisms. In both cases of periodic culture (microorganisms from biohumus and compost), nearly 100% of simazine (50 mg/l) was degraded (within 8 days). After the repeated enrichment culture with simazine, the rate of its degradation highly accelerated, and just after 24 h, the significant decrease of simazine (20% in compost and 80% in biohumus) was noted. Although a dozen attempts of isolating various strains responsible for biodegradation of simazine from compost and biohumus were performed, only the strain identified as Arthrobacter urefaciens (NC) was obtained, and it biodegraded simazine with almost 100% efficiency (within 4 days)

Orthopaedic management of Hurler’s disease after hematopoietic stem cell transplantation: a systematic review

The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the aim of the current study was to give a systematic overview of the orthopaedic complications and motor functioning of Hurler's patients after HSCT. A systematic review was conducted of the medical literature published from January 1981 to June 2010. Two reviewers independently assessed all eligible citations, as identified from the Pubmed and Embase databases. A pre-developed data extraction form was used to systematically collect information on the prevalence of radiological and clinical signs, and on the orthopaedic treatments and outcomes. A total of 32 studies, including 399 patient reports were identified. The most frequent musculoskeletal abnormalities were odontoid hypoplasia (72%), thoracolumbar kyphosis (81%), genu valgum (70%), hip dysplasia (90%) and carpal tunnel syndrome (63%), which were often treated surgically during the first decade of life. The overall complication rate of surgical interventions was 13.5%. Motor functioning was further hampered due to reduced joint mobility, hand dexterity, motor development and longitudinal growth. Stem cell transplantation does not halt the progression of a large range of disabling musculoskeletal abnormalities in Hurler's disease. Although prospective data on the quantification, progression and treatment of these deformities were very limited, early surgical intervention is often advocated. Prospective data collection will be mandatory to achieve better evidence on the effect of treatment strategies

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological materials covalently or engaging in redox-cycling reactions leading to the formation of other toxicants. Alternatively, they may result from the formation of a major metabolite with systemic exposure and adverse pharmacological activity. To avert such problems, biotransformation studies are becoming increasingly important in guiding the refinement of a lead series during drug discovery and in characterizing lead candidates prior to clinical evaluation. This article provides an overview of the methods that are used to uncover metabolism-related liabilities in a pre-clinical setting and offers suggestions for reducing such liabilities via the modification of structural features that are used commonly in drug-like molecules