Nevin Manimala

Huan Jing Ke Xue. 2021 Oct 8;42(10):4897-4907. doi: 10.13227/j.hjkx.202012118.

ABSTRACT

This study used 21 rock samples and 193 sets of paddy soil and rice grain samples collected form Baiwang Town, an area of clastic sedimentary rocks in Guangxi, China, to evaluate the potential for selenium-rich agriculture. We analyzed the concentrations of selenium and heavy metals in the soil and rice samples, and discuss the influencing factors by means of statistics and correlation analysis. The results showed that the selenium-rich rate of paddy soil and rice grain in Baiwang Town were 67.4% and 64.8%, respectively, but the content of cadmium in the selenium-rich soil samples was generally higher than the baseline value for China and the background value for Guangxi. In comparison to the screening value of soil pollution risk for agricultural land(GB 15618-2018), the over-standard rate of cadmium was 46.1%, while the over-standard rates of other heavy metals were negligible. The comparison shows that the selenium-rich rate of rice was 61.1% in the southern area of Baiwang Town with a negligible heavy metal content, and the advantages of green selenium-rich rice planting were clear. The correlation analysis showed that secondary enrichment was the main form of selenium enrichment in the study area. The soil pH and texture of the root-zone soil also affected the selenium content of the soil. The selenium content of rice seeds was mainly affected by the selenium content, active selenium content, pH, and aluminum oxide content of the root-zone soil. The risk assessment showed that the level of dietary exposure to cadmium is generally within safe limits, but it is still necessary to strengthen the monitoring of cadmium in rice and control cadmium pollution to reduce the levels of dietary exposure, especially in the central region of Baiwang Town.

PMID:34581133 | DOI:10.13227/j.hjkx.202012118

Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2105841118. doi: 10.1073/pnas.2105841118.

ABSTRACT

We present a comprehensive statistical framework to analyze data from genome-wide association studies of polygenic traits, producing interpretable findings while controlling the false discovery rate. In contrast with standard approaches, our method can leverage sophisticated multivariate algorithms but makes no parametric assumptions about the unknown relation between genotypes and phenotype. Instead, we recognize that genotypes can be considered as a random sample from an appropriate model, encapsulating our knowledge of genetic inheritance and human populations. This allows the generation of imperfect copies (knockoffs) of these variables that serve as ideal negative controls, correcting for linkage disequilibrium and accounting for unknown population structure, which may be due to diverse ancestries or familial relatedness. The validity and effectiveness of our method are demonstrated by extensive simulations and by applications to the UK Biobank data. These analyses confirm our method is powerful relative to state-of-the-art alternatives, while comparisons with other studies validate most of our discoveries. Finally, fast software is made available for researchers to analyze Biobank-scale datasets.

PMID:34580220 | DOI:10.1073/pnas.2105841118

Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2100117118. doi: 10.1073/pnas.2100117118.

ABSTRACT

How early human foragers impacted insular forests is a topic with implications across multiple disciplines, including resource management. Paradoxically, terminal Pleistocene and Early Holocene impacts of foraging communities have been characterized as both extreme-as in debates over human-driven faunal extinctions-and minimal compared to later landscape transformations by farmers and herders. We investigated how rainforest hunter-gatherers managed resources in montane New Guinea and present some of the earliest documentation of Late Pleistocene through mid-Holocene exploitation of cassowaries (Aves: Casuariidae). Worldwide, most insular ratites were extirpated by the Late Holocene, following human arrivals, including elephant birds of Madagascar (Aepyornithidae) and moa of Aotearoa/New Zealand (Dinornithiformes)-icons of anthropogenic island devastation. Cassowaries are exceptional, however, with populations persisting in New Guinea and Australia. Little is known of past human exploitation and what factors contributed to their survival. We present a method for inferring past human interaction with mega-avifauna via analysis of microstructural features of archaeological eggshell. We then contextualize cassowary hunting and egg harvesting by montane foragers and discuss the implications of human exploitation. Our data suggest cassowary egg harvesting may have been more common than the harvesting of adults. Furthermore, our analysis of cassowary eggshell microstructural variation reveals a distinct pattern of harvesting eggs in late ontogenetic stages. Harvesting eggs in later stages of embryonic growth may reflect human dietary preferences and foraging seasonality, but the observed pattern also supports the possibility that-as early as the Late Pleistocene-people were collecting eggs in order to hatch and rear cassowary chicks.

PMID:34580213 | DOI:10.1073/pnas.2100117118

Neurol Neuroimmunol Neuroinflamm. 2021 Sep 27;8(6):e1061. doi: 10.1212/NXI.0000000000001061. Print 2021 Nov.

ABSTRACT

BACKGROUND AND OBJECTIVES: To determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.

METHODS: Pregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients’ or controls’ IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls’ IgG, patients’ IgG, or patients’ IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.

RESULTS: In pregnant mice that received patients’ IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients’ IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.

DISCUSSION: FcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients’ antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy.

PMID:34580181 | DOI:10.1212/NXI.0000000000001061

Respir Care. 2021 Sep 27:respcare.09244. doi: 10.4187/respcare.09244. Online ahead of print.

ABSTRACT

Background: Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select and the severely ill. The vibrating mesh nebulizer (VMN) was previously demonstrated to be an effective alternative to the small particle aerosol generator (SPAG) in particle size, chemical makeup, and concentrations of the ribavirin pre and post nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin’s activity pre and post nebulization via VMN. Methods: We grew and infected human epithelial type 2 cells (HEp2) and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. Results: Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. Conclusions: The VMN nebulizer does not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the VMN in the administration of inhaled ribavirin.

PMID:34580175 | DOI:10.4187/respcare.09244

J Investig Med. 2021 Sep 27:jim-2021-001948. doi: 10.1136/jim-2021-001948. Online ahead of print.

ABSTRACT

Early studies have reported various electrolyte abnormalities at admission in patients with severe COVID-19. 104 out of 193 patients admitted to our institution presented with hypermagnesemia at presentation. It is believed this may be important in the evaluation of severe SARS-CoV-2 infections. This study evaluated the outcomes of hypermagnesemia in patients with COVID-19. A retrospective chart review of patients admitted to the hospital with confirmed SARS-CoV-2 infection was conducted. A review of the medical literature regarding hypermagnesemia, magnesium levels in critical care illness and electrolyte abnormalities in patients with COVID-19 was performed. Differences in demographic and clinical characteristics of patients with hypermagnesemia and normomagnesemia were evaluated using descriptive statistics. Other known variables of disease severity were analyzed. 104 patients (54%) were identified with hypermagnesemia (≥2.5 mg/dL). 48 of those patients were admitted to the intensive care unit (46%, p<0.001). 34 patients required ventilator support (32%, p<0.0001). With age-adjusted logistic regression analysis hypermagnesemia was associated with mortality (p=0.007). This study demonstrates that hypermagnesemia is a significant marker of disease severity and adverse outcome in SARS-CoV-2 infections. We recommend serum magnesium be added to the panel of tests routinely ordered in evaluation of severe SARS-CoV-2 infections.

PMID:34580159 | DOI:10.1136/jim-2021-001948

J Immunol. 2021 Sep 27:ji2100686. doi: 10.4049/jimmunol.2100686. Online ahead of print.

ABSTRACT

Autoimmune diseases develop when autoantigens activate previously quiescent self-reactive lymphocytes. Gene-gene interaction between certain HLA class I risk alleles and variants of the endoplasmic reticulum aminopeptidase ERAP1 controls the risk for common immune-mediated diseases, including psoriasis, ankylosing spondylitis, and Behçet disease. The functional mechanisms underlying this statistical association are unknown. In psoriasis, HLA-C*06:02 mediates an autoimmune response against melanocytes by autoantigen presentation. Using various genetically modified cell lines together with an autoreactive psoriatic TCR in a TCR activation assay, we demonstrate in this study that in psoriasis, ERAP1 generates the causative melanocyte autoantigen through trimming N-terminal elongated peptide precursors to the appropriate length for presentation by HLA-C*06:02. An ERAP1 risk haplotype for psoriasis produced the autoantigen much more efficiently and increased HLA-C expression and stimulation of the psoriatic TCR by melanocytes significantly more than a protective haplotype. Compared with the overall HLA class I molecules, cell surface expression of HLA-C decreased significantly more upon ERAP1 knockout. The combined upregulation of ERAP1 and HLA-C on melanocytes in psoriasis lesions emphasizes the pathogenic relevance of their interaction in patients. We conclude that in psoriasis pathogenesis, the increased generation of an ERAP1-dependent autoantigen by an ERAP1 risk haplotype enhances the likelihood that autoantigen presentation by HLA-C*06:02 will exceed the threshold for activation of potentially autoreactive T cells, thereby triggering CD8⁺ T cell-mediated autoimmune disease. These data identify ERAP1 function as a central checkpoint and promising therapeutic target in psoriasis and possibly other HLA class I-associated diseases with a similar genetic predisposition.

PMID:34580106 | DOI:10.4049/jimmunol.2100686

BMJ Open. 2021 Sep 27;11(9):e054213. doi: 10.1136/bmjopen-2021-054213.

ABSTRACT

In a cluster randomised trial (CRT), intact groups-such as communities, clinics or schools-are randomised to the study intervention or control conditions. The issue of informed consent in CRTs has been particularly challenging for researchers and research ethics committees. Some argue that cluster randomisation is a reason not to seek informed consent from research participants. In fact, systematic reviews have found that, relative to individually randomised trials, CRTs are associated with an increased likelihood of inadequate reporting of consent procedures and inappropriate use of waivers of consent. The objective of this paper is to clarify this confusion by providing a practical and useful framework to guide researchers and research ethics committees through consent issues in CRTs. In CRTs, it is the unit of intervention-not the unit of randomisation-that drives informed consent issues. We explicate a three-step framework for thinking through informed consent in CRTs: (1) identify research participants, (2) identify the study element(s) to which research participants are exposed, and (3) determine if a waiver of consent is appropriate for each study element. We then apply our framework to examples of CRTs of cluster-level, professional-level and individual-level interventions, and provide key lessons on informed consent for each type of CRT.

PMID:34580104 | DOI:10.1136/bmjopen-2021-054213

BMJ Open. 2021 Sep 27;11(9):e052221. doi: 10.1136/bmjopen-2021-052221.

ABSTRACT

OBJECTIVE: To determine the prevalence of tuberculosis (TB) and HIV in 13 Zambian correctional facilities.

METHODS: Cross-sectional study.

SETTING: 13 correctional facilities in seven of the 10 provinces in Zambia.

PARTICIPANTS: All incarcerated individuals were eligible for TB and HIV screening and testing. Of the total study population of 9695 individuals, which represent 46.2% of total correctional population at the beginning of the study, 8267 and 8160 were screened for TB and HIV, respectively.

INTERVENTIONS: TB and HIV screening and testing was done between July 2018 and February 2019.

PRIMARY OUTCOME MEASURES: All forms of TB, bacteriologically confirmed TB, drug-resistant TB, HIV.

RESULTS: Prevalence of all forms of TB and bacteriologically confirmed TB was 1599 (1340-1894) per 100 000 population and 1056 (847-1301) per 100 000 population, respectively. Among those with bacteriologically confirmed TB, 4.6% (1.3%-11.4%) had drug-resistant TB.There was no statistically significant difference in the prevalence of all forms of TB, bacteriologically confirmed TB and drug resistant TB between adults and juveniles: (p=0.82), (p=0.23), (p=0.68) respectively. Of the bacteriologically confirmed TB cases, 28.7% were asymptomatic. The prevalence of HIV was 14.3% (13.6%-15.1%). The prevalence of HIV among females was 1.8 times the prevalence of HIV among males (p=0.01).

CONCLUSION: Compared with the study in 2011 which screened inmates representing 30% of the country’s inmate population, then the prevalence of all forms of TB and HIV in correctional facilities has reduced by about 75% and 37.6%, respectively. However, compared with the general population, the prevalence of all forms of TB and HIV was 3.5 and 1.3 times higher, respectively. TB/HIV programmes in correctional facilities need further strengthening to include aspects of juvenile-specific TB programming and gender responsive HIV programming.

PMID:34580101 | DOI:10.1136/bmjopen-2021-052221

BMJ Open. 2021 Sep 27;11(9):e046912. doi: 10.1136/bmjopen-2020-046912.

ABSTRACT

INTRODUCTION: For people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles.

METHODS AND ANALYSIS: The study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals’ risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up.

ETHICS AND DISSEMINATION: This study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.

PMID:34580091 | DOI:10.1136/bmjopen-2020-046912