Nevin Manimala

J Glob Health. 2022 Aug 17;12:04065. doi: 10.7189/jogh.12.04065.

ABSTRACT

BACKGROUND: The spread of COVID-19 exposed the inadequacies inherent in the health care systems of many countries. COVID-19 and the attendant demands for emergency treatment and management put a significant strain on countries’ health care systems, including hitherto strong health systems. In Uganda, as the government strived to contain COVID-19, other essential health care services were either disrupted or completely crowded out. Balancing the provision of COVID-19 treatment and management services and at the same time offering sexual and reproductive health and rights services (SRHR) proved to be a considerable challenge in these circumstances. COVID-19 prevention-related travel restrictions and border closures had far-reaching negative consequences on the mobility of individuals to access essential health services in Uganda. The situation may have been worse for cross-border communities that sometimes access services across the borders.

METHODS: Using quantitative data from 1521 respondents and qualitative data (20 key informant interviews and 12 focus group discussions), we investigate the disruption in accessing SRHR services for border communities in Uganda during COVID-19.

RESULTS: Results indicate that females (adjusted odds ratio (aOR) = 1.3; 95% confidence interval CI = 1.08-1.79), those with primary education (aOR = 1.47; 95% CI = 1.61-2.57), currently employed (aOR = 2.03; 95% CI = 1.61-2.57) and those with the intention to leave current residence (aOR = 2.09; 95% CI = 1.23-3.55) were more likely to have experienced a disruption in accessing SRHR services. However, respondents aged 35 years, or more were less likely to have experienced a disruption compared to their younger counterparts.

CONCLUSIONS: Results shed light on the disruption of access toSRHR services during pandemics such as COVID-19 among a highly mobile population. There is a need to invest in building strong and resilient health care systems that can guarantee continuous access to essential health services including SRHR provisions among mobile populations during pandemics.

PMID:35972848 | DOI:10.7189/jogh.12.04065

Pediatr Obes. 2022 Aug 16:e12968. doi: 10.1111/ijpo.12968. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood obesity rates are on the rise, but there are currently no effective therapies available to slow or halt their progression. Although environmental and lifestyle factors have been implicated in its pathogenesis, childhood obesity is considered a complex disorder with a clear genetic component. Intense genome-wide association study (GWAS) efforts through large-scale collaborations have enabled the discovery of genetic loci robustly associated with childhood obesity beyond the classic FTO locus. That said, GWAS itself does not pinpoint the actual underlying causal effector genes, but rather just yields association signals in the genome.

OBJECTIVE: This review aims to outline what has been elucidated thus far on the genetic aetiology of commong childhood obesity and to describe strategies to identify and validate both causal common genetic variants and their corresponding effector genes.

RESULTS: Relevant cell types for molecular studies can be identified by gene set enrichment analysis and considering known biology of obesity-related physiological processes. Putatively causal single nucleotide polymorphisms (SNPs) can be identified by several methods including statistical fine mapping and ‘assay for transposase accessible chromatin sequencing’ (ATAC-seq). Variant to gene mapping can then nominate effector genes likely regulated by cis-regulatory elements harbouring putatively causal SNPs. A SNP’s cis-regulatory activity can be functionally validated by several in vitro methods including luciferase assay and CRISPR approaches. These CRISPR approaches can also be used to investigate how dysregulatn of effector genes may confer obesity risk.

CONCLUSION: Uncovering the causative genes related to GWAS signals and elucidating their functional contributions to paediatric obesity with these strategies will deepen our understanding of this disease and serve better treatment outcomes.

PMID:35971868 | DOI:10.1111/ijpo.12968

Artif Organs. 2022 Aug 16. doi: 10.1111/aor.14387. Online ahead of print.

ABSTRACT

BACKGROUND: The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers.

METHODS: A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C-cuff electrode and I-beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in-vitro and in-vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in-vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability.

RESULTS: Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500μm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in-vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1×10^-2 cm² . Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre- versus post-stimulation impedance measurements were not significantly different (p-value >0.05) CONCLUSIONS: The new cuff electrode enables rapid development of cost-effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low-frequency current targeted within the peripheral nervous system.

PMID:35971860 | DOI:10.1111/aor.14387

Aliment Pharmacol Ther. 2022 Aug 16. doi: 10.1111/apt.17191. Online ahead of print.

ABSTRACT

BACKGROUND: Autoimmune hepatitis (AIH) may coexist with metabolic syndrome-associated diseases (MSADs) given patients’ inherent need for corticosteroid therapy, as well as general population trends.

AIM: To examine the impact of MSAD risk factors on AIH or its treatment, and vice versa METHODS: This was a multi-centre retrospective cohort study of 552 patients with AIH diagnosed between January 2000 and December 2019. Data relating to demographic factors, laboratory values, AIH medications and MSADs were collected at diagnosis and at 1- and 3-year follow-up. Statistical relationships were analysed and reported.

RESULTS: We included 552 patients in the study cohort (median age 50 years, 76.1% female). All MSADs, including hypertension, dyslipidaemia, diabetes and a gain of BMI ≥3 kg/m² , increased within the AIH cohort over time. Initial treatment regimen impacted de novo diabetes but not other MSAD development. AIH biochemical remission was less frequent at 3 years post-diagnosis among patients with ≥1 MSAD. The incidence of new MSADs could be predicted by baseline factors in certain cases.

CONCLUSION: In the largest US-based cohort of patients newly diagnosed with AIH, there was a considerable burden of pre-existing and de novo MSADs that may affect AIH treatment outcomes. Identifying those at highest risk of co-morbid MSADs allows for an individualised approach to management to reduce its long-term sequelae in patients with AIH.

PMID:35971856 | DOI:10.1111/apt.17191

Allergy. 2022 Aug 16. doi: 10.1111/all.15480. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T cell subpopulations are involved. These cells express specific miRNAs (i.e., inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients.

METHODS: Samples from healthy donors (N=30) and patients (N=119) with different asthma endotypes (T2^high -Atopic/T2^high -Non atopic/T2^low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR.

RESULTS: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p, and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2^high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the other hand, IL-6^high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p, and miR-146a-5p.

CONCLUSION: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p, and miR-215-5p can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.

PMID:35971848 | DOI:10.1111/all.15480

Am Surg. 2022 Aug 16:31348221121547. doi: 10.1177/00031348221121547. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty is associated with adverse surgical outcomes including post-operative complications, needs for post-acute care, and mortality. While multiple frailty screening tools exist, most are time and resource intensive. Here we examine the association of an automated electronic frailty index (eFI), derived from routine data in the Electronic Health Record (EHR), with outcomes in vascular surgery patients undergoing open, lower extremity revascularization.

METHODS: A retrospective analysis at a single academic medical center from 2015 to 2019 was completed. Information extracted from the EHR included demographics, eFI, comorbidity, and procedure type. Frailty status was defined as fit (eFI≤0.10), pre-frail (0.10<eFI≤0.21), and frail (eFI>0.21). Outcomes included length of stay (LOS), 30-day readmission, and non-home discharge.

RESULTS: We included 295 patients (mean age 65.9 years; 31% female), with the majority classified as pre-frail (57%) or frail (32%). Frail patients exhibited a higher degree of comorbidity and were more likely to be classified as American Society of Anesthesiologist class IV (frail: 46%, pre-frail: 27%, and fit: 18%, P = 0.0012). There were no statistically significant differences in procedure type, LOS, or 30-day readmissions based on eFI. Frail patients were more likely to expire in the hospital or be discharged to an acute care facility (31%) compared to pre-frail (14%) and fit patients (15%, P = 0.002). Adjusting for comorbidity, risk of non-home discharge was higher comparing frail to pre-frail patients (OR 3.01, 95% CI 1.40-6.48).

DISCUSSION: Frail patients, based on eFI, undergoing elective, open, lower extremity revascularization were twice as likely to not be discharged home.

PMID:35971786 | DOI:10.1177/00031348221121547

J Card Surg. 2022 Aug 16. doi: 10.1111/jocs.16840. Online ahead of print.

ABSTRACT

BACKGROUND: Outcomes of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients with aortic stenosis and bicuspid aortic valve (BAV) must be better investigated.

METHODS: A meta-analysis including studies published by January 2022 reporting immediate outcomes (in-hospital death, stroke, acute kidney injury [AKI], major bleeding, new permanent pacemaker implantation [PPI], paravalvular leakage [PVL]), mortality in the follow-up (with Kaplan-Meier curves for reconstruction of individual patient data).

RESULTS: Five studies met our eligibility criteria. No statistically significant difference was observed for in-hospital death, stroke, AKI, and PVL. TAVI was associated with lower risk of major bleeding (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.12-0.69; p = .025), but higher risk of PPI (OR: 2.00; 95% CI: 1.05-3.77; p = .041). In the follow-up, mortality after TAVI was significantly higher in the analysis with the largest samples (HR: 1.24, 95% CI: 1.01-1.53, p = .043), but no statistically significant difference was observed with risk-adjusted populations (HR: 1.06, 95% CI: 0.86-1.32, p = .57). Landmark analyses suggested a time-varying risk with TAVI after 10 and 13 months in both largest and risk-adjusted populations (HR: 2.13, 95% CI: 1.45-3.12, p < .001; HR: 1.7, 95% CI: 1.11-2.61, p = .015, respectively).

CONCLUSION: Considering the immediate outcomes and comparable overall survival observed in risk-adjusted populations, TAVI can be used safely in selected BAV patients. However, a time-varying risk is present (favoring SAVR over TAVI at a later timepoint). This finding was likely driven by higher rates of PPI with TAVI.

PMID:35971783 | DOI:10.1111/jocs.16840

Huan Jing Ke Xue. 2022 Aug 8;43(8):4199-4211. doi: 10.13227/j.hjkx.202112133.

ABSTRACT

Taking the Jianghugongmi producing area as the research object, As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil of the study area were sampled and determined. The correlation of heavy metals was discussed using the multivariate statistical method, the spatial distribution interpolation analysis of heavy metals was carried out using ArcGIS 10.2, the quantitative source analysis of heavy metal pollution was carried out using the enrichment factor (EF) and PMF methods, and the potential ecological risk was evaluated. The results showed that the contents of the soil heavy metals As, Cd, Cu, Hg, Pb, and Zn were lower than the screening values specified in the standard for soil pollution risk control of agricultural land (GB 15618-2018), and the soil ecological environment risk was low; the maximum values of Cr and Ni exceeded the risk screening values, but the risk was low. The main distribution range of pH in the study area was 6.05-6.69, which was suitable for rice growth. The Mohe River indicated the spatial distribution of pH and heavy metals, which was closely related to the supergene geochemical characteristics of the elements. However, Hg and Cd showed different spatial distribution characteristics under human influence. Hg was distributed in the middle and high value distribution area along the west side of the river, and the spatial distribution of Cd was significantly different from north to south. The quantitative source analysis results based on the EF method and PMF showed that the main sources of heavy metals in the study area were agricultural sources, mixed sources, coal sources, and natural sources. The contribution rates of various sources accounted for 24.2%, 35.4%, 9.5%, and 30.9%, respectively. The medium strong ecological risk points of Hg in the study area were distributed along the west side of the Mohe River, whereas the moderate potential ecological risk points of Cd were concentrated in the cultivated land on both sides of the Mohe River, and the potential ecological risk index (E_r) of the other elements was<40. Cd and Hg were the main potential ecological risk elements in the study area, whereas Cd was still the main potential pollution element in the cultivated land soil in the study area.

PMID:35971717 | DOI:10.13227/j.hjkx.202112133

Huan Jing Ke Xue. 2022 Aug 8;43(8):4179-4189. doi: 10.13227/j.hjkx.202109180.

ABSTRACT

Shizuishan is a typical exhausted resources-based city in the northern area of the Ningxia Hui autonomous region in China. In order to develop the planting industry of selenium (Se)-rich agricultural products and promote green and sustainable urban development and transformation, investigations on the quality of Se-rich land were carried out in Shizuishan City, where 7399 surface soil (0-20 cm) samples of farmlands, 30 atmospheric precipitation samples, and nine parent rocks were collected. By means of semi variogram model construction by GS⁺, Kriging interpolation in ArcGIS and statistics via SPSS, such as correlation analysis and mean-value analysis, the content, spatial distribution, and enrichment factors of Se-soil were analyzed. Further, the enrichment characteristics of soil Se in alkaline conditions were summarized. The results indicated that ω(Se) in surface soil was (0.26±0.12) mg·kg^-1, and its spatial distribution was highly auto-correlated. The variation in Se content was related to natural factors. Along Helan Mountain, the content of Se in the surface soil was comparatively higher than that where coal mines were located. The parent rock was the principal factor that controlled the enrichment of soil Se. The physical and chemical properties of soil such as organic material, pH, and iron and manganese oxides had crucial effects on the enrichment of soil Se in a surficial environment. Compared to a strong alkaline environment, alkaline conditions were beneficial for the enrichment of Se in the surface soil.

PMID:35971715 | DOI:10.13227/j.hjkx.202109180

Huan Jing Ke Xue. 2022 Aug 8;43(8):4054-4063. doi: 10.13227/j.hjkx.202110174.

ABSTRACT

The pollution source identification methods based on traditional water quality monitoring and pollutant discharge loading typically require a high frequency of monitoring and generate a level of uncertainty in the identification results, owing to their limitations on the accurate and quantitative assessment of pollution source identification, migration, and transformation. This study combined multivariate statistical analysis and stable isotope technology to identify groundwater pollution sources in a typical multiple land-use area of the Chengdu Plain. A positive matrix factorization (PMF) model was adopted to reduce the interference of mass environmental factors on source identification and to determine the main factors influencing groundwater quality. Subsequently, a Bayesian stable isotope mixing model was developed to quantify the apportionment of each pollution source to groundwater nitrate (NO₃^–) with the consideration of hydro-chemical and land-use information. The results showed that the concentrations of NO₃^–, NO₂^–, NH₄⁺, Mn, Fe, SO₄^2-, and Cl^– in groundwater of the study area exceeded the standard to different extents, presenting spatial variation. The main form of inorganic nitrogen in groundwater was NO₃^–. In general, concentrations of groundwater NO₃^– were the highest in vegetable fields (9.29 mg·L^-1 on average), followed by livestock and poultry breeding farms (7.66 mg·L^-1) and arable land (7.09 mg·L^-1), whereas concentrations of groundwater NO₃^– in industrial areas were the lowest (2.20 mg·L^-1). Groundwater quality in the study area was affected by geological processes, agricultural activities, hydrogeochemical evolution, and domestic and industrial discharges. Agricultural activities were the main contributor to the increase in groundwater NO₃^– in the study area. Chemical fertilizer (32%) and soil nitrogen (25%) contributed greatly to groundwater NO₃^– in agricultural areas, whereas sewage (28%) and atmospheric precipitation (27%) contributed most groundwater NO₃^– in industrial areas. Thus, the combination of multivariate statistical analysis and stable isotope technology could identify groundwater pollution sources and their apportionment effectively, providing scientific support for the prevention and control of groundwater pollution.

PMID:35971703 | DOI:10.13227/j.hjkx.202110174