Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Rationale, Design and Baseline Characteristics of a Randomized Controlled Trial of a Cardiovascular Quality Improvement Strategy in India: The C-QIP Trial.

BACKGROUND: Quality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India. METHODS: The C-QIP is a clinic-based, open randomized trial of a multicomponent intervention vs usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained nonphysician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (ie, dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines. RESULTS: We recruited 410 socio-demographically diverse patients with CVD from 4 hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure. CONCLUSION: This study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings. TRIAL REGISTRATION: Clinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659.

Adsorptive removal of naproxen onto nano magnesium oxide-modified castor wood biochar: Treatment of pharmaceutical wastewater via sequential Fenton's-adsorption process.

This current investigation explored the thermal conversion process of castor wood into biochar, which was subsequently harnessed for removing naproxen from pharmaceutical industrial effluent via adsorption. Surface composition analyses conducted through scanning electron microscopy-energy dispersive X-ray, laser-induced breakdown spectroscopy, and Fourier-transform infrared studies unveiled the presence of nano MgO particles within the adsorbent material. Employing optimization techniques such as response surface methodology facilitated a refined approach to batch study. The optimized conditions for batch naproxen sodium (NPX) adsorption on nano-MgO-modified biochar were identified as pH 4, 1.5 g/L adsorbent dosage, and a 120-min contact time maintaining a constant NPX concentration of 10 mg/L. The adsorption capacity was calculated to be 123.34 mg/g for a nano-magnesium oxide-modified castor wood biochar (modified biochar) and 99.874 mg/g for pristine castor wood biochar (pristine biochar). Fenton's reagents comprising 15 mM of FeSO4 (7H2O) and 25 mM of H2O2 have been scrutinized under conditions of pH 3.0, a reaction time of 30 min, a temperature of 30°C, and stirring at 120 rpm, followed by batch adsorption treatment. The COD, NH3-N, NO3 -, PO4 3-, and NPX removal percentages was found to be 90%, 87%, 79%, 80%, and 90%, respectively. Thus nano MgO-modified biochar holds promise of treatment of pharmaceutical effluent.

MicroRNAs as promising drug delivery target to ameliorate chronic obstructive pulmonary disease using nano-carriers: a comprehensive review.

Chronic obstructive pulmonary disease (COPD) is a deteriorating condition triggered by various factors, such as smoking, free radicals, and air pollution. This worsening disease is characterized by narrowing and thickening of airways, painful cough, and dyspnea. In COPD, numerous genes as well as microRNA (miRNA) play a significant role in the pathogenesis of the disease. Many in vivo and in vitro studies suggest that upregulation or suppression of certain miRNAs are effective treatment options for COPD. They have been proven to be more beneficial than the current symptomatic treatments, such as bronchodilators and corticosteroids. MiRNAs play a crucial role in immune cell development and regulate inflammatory responses in various tissues. MiRNA treatment thus allows for precision therapy with improved outcomes. Nanoparticle drug delivery systems such as polymeric nanoparticles, inorganic nanoparticles, dendrimers, polymeric micelles, and liposomes are an efficient method to ensure the biodistribution of the miRNAs to the target site. Identification of the right nanoparticle depending on the requirements and compatibility is essential for achieving maximum therapeutic effect. In this review, we offer a thorough comprehension of the pathology and genetics of COPD and the significance of miRNAs concerning various pathologies of the lung, as potential targets for treating the disease. The present review offers the latest insights into the nanoparticle drug delivery systems that can efficiently carry and deliver miRNA or antagomirs to the specific target site and hence help in effective management of COPD.

5H-benzo[c]fluorene derivative exhibits antiproliferative activity via microtubule destabilization.

Present study aimed at a single component cyclization of 2-benzylidene-1-tetralones for the preparation of 5H-benzo[c]fluorenes and their antiproliferative activity. This ring closure reaction underwent via reductive cyclization in the presence of a sodium borohydride-aluminium chloride system. Ten diverse 5H-benzo[c]fluorene derivatives were prepared and evaluated for antiproliferative activity against three human cancer cell lines by SRB assay. Four of these benzofluorenes exhibited significant antiproliferative effect with an IC50 < 10.75 µM. The best representative compound 21, exhibited IC50 against K562 leukemic cells at 3.27 µM in SRB assay and 7.68 µM in Soft agar colony assay. It exhibited a microtubule destabilization effect in tubulin kinetics and inhibited 82.9 % microtubule polymer mass at 10 µM concentration in Protein Sedimentation assay (Microtubule). Compound 21 exerted G0/G1 phase arrest in cell division cycle analysis in K562 cells. It also induced apoptosis in K562 cells via activation of Caspase cascade pathway. Furthermore, compound 21 also possessed anti-inflammatory activity by inhibiting TNF-α and IL-6 moderately. It exhibited significant in vivo efficacy and reduced K562 tumour in xenograft mice by 47 % at an 80 mg/kg oral dose. Further, it was found to be safe and well tolerable up to 1000 mg/kg in Swiss albino mice. Compound 21 needs to be optimized for better in vivo efficacy in rodent models for further development.

Hyphenated Fenton-column packed nMnO-modified wood biochar for tannery effluent treatment: Adsorption mechanism and reusability study.

Industrial wastewater contains a wide range of pollutants that, if released directly into natural ecosystems, have the potential to pose serious risks to the environment.This study aims to investigate sustainable and efficient approaches for treating tannery wastewater, employing a combination of hyphenated Fenton oxidation and adsorption processes. Rigorous analyses were conducted on wastewater samples, evaluating parameters like COD, sulphide, NH3-N, PO43-, NO3-, and Cr(VI). The performance of this adsorbent material was gauged through column adsorption experiments. A comprehensive characterization of the adsorbent was undertaken using techniques such as SEM, EDX, BET, FTIR, XRD, and LIBS. The study delved into varying operational parameters like bed depth (ranging from 3.5 to 9.5 cm) diameter (2.5 cm) and influent flow rate (ranging from 5 to 15mLmin-1). The experimental outcomes revealed that increasing the bed depth and decreasing the influent flow rate significantly bolstered the adsorption column's effectiveness. Breakthrough curves obtained were fitted with different models, including the Thomas and Yoon-Nelson models. The most optimal column performance was achieved with a bed height of 10.5 cm and a flow rate of 5mLmin-1. The combined process achieved removal efficiencies of 94.5% for COD, 97.4% for sulphide, 96.2% for NH3-N, 83.1% for NO3-, 79.3% for PO43-, and 96.9% for Cr(VI) in tannery effluent. This research presents a notable stride toward the development of sustainable and efficient strategies for tannery wastewater treatment.

Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer: retrospective study in a multi-ethnic population.

OBJECTIVES: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. METHODS: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. RESULTS: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). CONCLUSION: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.

Acute metformin induces hyperglycemia in healthy adult mourning doves, Zenaida macroura.

Birds have the highest blood glucose among vertebrates. Several mechanisms may explain this including the lack of a functional insulin-responsive glucose transport protein, high glucagon concentrations, and reliance on lipid oxidation resulting in the production of gluconeogenic precursors. The hypothesis was that interruption of gluconeogenesis using the diabetes medication metformin would lower glucose concentrations in wild-caught birds. We captured two cohorts of adult mourning doves, Zenaida macroura, and acclimated them to captivity for two weeks. In this crossover study, cohort 1 was administered a single dose of one of the following oral treatments each week: metformin (150 or 300 mg/kg), glycogenolysis inhibitor (2.5 mg/kg 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)), or water (50 µL). Whole blood glucose was measured using a glucometer at baseline, 30, 60, and 120 min following the oral doses. In contrast to mammals and chickens, 300 mg/kg metformin did not alter blood glucose (p > 0.05) whereas 150 mg/kg metformin increased blood glucose compared to water (p = 0.043). To examine whether 150 mg/kg metformin stimulated glycogenolysis, we co-administered 150 mg/kg metformin and 2.5 mg/kg DAB, which prevented the hyperglycemic response. Cohort 2 was administered the same treatments and the early response was examined (0, 5, 10, 15 min). Low-dose metformin increased blood glucose within 5 min (p = 0.039) whereas the high dose had no effect. DAB did not prevent the early response to metformin nor did it alter blood glucose concentrations when administered alone (p = 0.887). In conclusion, metformin increases endogenous blood glucose via glycogenolysis in healthy adult male mourning doves.

Development and Characterization of Modified Chitosan Lipopolyplex for an Effective siRNA Delivery.

Cytotoxicity, speedy degradation, and limited cellular absorption are the foremost features influencing the successful delivery of RNAs. Chitosan (Cs) is a polymer that offers an advantage due to its bio-compatibility and biodegradable nature, making it an ideal polycationic vector for delivering siRNA. In this study, chitosan has been modified with arginine in order to increase its encapsulation of siRNA and improve cellular absorption. It was discovered that arginine and guanidino moieties could transport through membranes of cells and play an important part in membrane permeability. FTIR and 13C NMR were used to characterize the complex. These chitosan-arginine (CsAr) siRNA complexes are further encapsulated in anionic DPPC/cholesterol liposomes to combine the effects of liposome-chitosan-arginine complexes called lipopolyplexes (LCAr). Formed LCAr were investigated for their lipid/CsAr-siRNA ratios, size, zeta-potential, heparin, and serum RNase stability by agarose gel retardation, and cell uptake efficiency compared to their "parent" polyplexes. Results revealed complete lipidation of CsAr-siRNA polyplexes at lipid mass ratio 10 resulting in lipopolyplexes in the 120 to 230nm range. Polyplex entrapped ~70% of siRNA, whereas lipidation increases siRNA encapsulation to ~95%. Developed LCAr showed ~4 times less hemolytic potential as compared to the parent polyplexes at the highest siRNA dose. The CsAr-siRNA and its lipid-coated form showed enhanced cellular association as compared to the marketed Lipofectamine 2000 proving its effectiveness in siRNA delivery. CsAr-liposome conjugation is simple and safe, and serves as a robust carrier for gene transport in physiological situations without compromising transfection efficacy.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

Cardiovascular health metrics in low and middle-income countries: A scoping review.

BACKGROUND: In 2010 the American Heart Association defined the concept of ideal cardiovascular health to renew the focus on primordial prevention for cardiovascular disease. Evidence primarily from high-income countries suggests ideal CVH prevalence is low and decreases with age, with vulnerable populations differentially affected. We aimed to identify and characterize the evidence relevant to CVH metrics in low- and middle-income countries (LMICs). METHODS: We followed the Joanna Briggs Institute guideline for the conduct of this scoping review. We searched MEDLINE, Embase, LILACS and study registers from inception to 14 March 2022. We included cross-sectional and cohort studies in populations representing a geographically-defined unit (urban or rural) in LMICs, and with data on CVH metrics i.e. all health or clinical factors (cholesterol, blood pressure, glycemia and body mass index) and at least one health behavior (smoking, diet or physical activity). We report findings following the PRISMA-Scr extension for scoping reviews. RESULTS: We included 251 studies; 85% were cross-sectional. Most studies (70.9%) came from just ten countries. Only 6.8% included children younger than 12 years old. Only 34.7% reported seven metrics; 25.1%, six. Health behaviors were mostly self-reported; 45.0% of studies assessed diet, 58.6% physical activity, and 90.0% smoking status. CONCLUSIONS: We identified a substantial and heterogeneous body of research presenting CVH metrics in LMICs. Few studies assessed all components of CVH, especially in children and in low-income settings. This review will facilitate the design of future studies to bridge the evidence gap. This scoping review protocol was previously registered on OSF: https://osf.io/sajnh.

Characterizing variability in total mercury hair:blood ratio in the general Canadian population.

BACKGROUND/OBJECTIVES: The body burden of mercury in humans can be measured through hair or blood biomarkers. To compare results from different studies, it is often required to convert mercury in hair to an equivalent level in blood, using a default hair:blood ratio of 250:1 by the World Health Organization (WHO). However, the actual ratio may vary within and between populations. The objectives of this study were to analyze the hair:blood mercury ratio in the general Canadian population, explore factors associated with higher/lower ratios, and determine if the standard ratio of 250:1 is supported. METHODS: The Canadian Health Measures Survey (CHMS) Cycle 5 (2016-2017) measured total mercury (THg) in both hair and blood of 1168 participants 20-59 years of age. We calculated geometric mean (GM) concentrations of THg for this entire sample and subgroups. The subgroups included biological sex, women of childbearing age, race, hair treatments, categories of blood and hair selenium, urinary arsenobetaine/arsenocholine, categories of blood and hair mercury, and food consumption. We calculated a hair:blood ratio for each participant and determined population-level ratios from the GMs of the distributions. Differences by subgroups, and agreement with the WHO ratio of 250:1, were tested. The combined effect of factors on the THg hair:blood ratio was explored using staged regression analysis. RESULTS: For participants with paired hair and blood mercury measurements, the GM of the hair:blood THg ratio was 293 (95%CI:273-316), and significantly >250. In women of childbearing age, the ratio did not differ from 250. The GMs of the ratio were higher (i.e.>300) for second tertile blood selenium (365, 95%CI:307-433), third and fourth quartiles hair mercury (347, 95%CI:308-390 and 376, 95%CI:336-422), and consumers of shellfish (338, 95%CI:308-371). Shellfish consumption was the only statistically significant factor associated with the hair:blood ratio as identified in the regression model. CONCLUSIONS: The mean hair:blood THg ratio among Canadians generally exceeded the default ratio of 250:1. Higher ratios were observed in certain subgroups, such as seafood consumers, and shellfish consumption was the most important variable associated with the ratio. Our results suggest that population-specific hair:blood THg ratios be considered, if possible, when converting mercury levels from hair to blood to better characterize the variation around the conversion.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children.

BACKGROUND: Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. OBJECTIVE: To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. METHODS: We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3-4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0-2, moderate: 3-7, or high: ≥8 times/month). RESULTS: Higher cord blood Hg concentrations were associated with lower PIQ (ß = -3.27; 95%CI: 6.44, -0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. CONCLUSIONS: Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake.

Increasing health facility childbirth in Ghana: the role of network and community norms.

BACKGROUND: Reducing pregnancy-related deaths in Sub-Saharan Africa through increases in health facility births may be achieved by promoting community norms and network norms favoring health facility births. However, the process of how both norms shift attitudes and actions towards facility delivery is little studied. We examined the association of network and community norms with facility birth, following a quality improvement intervention to improve facility births in Ghana. METHODS: A 2015 mixed methods evaluation of a Maternal and Newborn Health Referral (MNHR) project in Ghana included a cross-sectional survey of women (N = 508), aged 15-49 years; in-depth interviews (IDIs) with mothers (n = 40), husbands (n = 20) and healthcare improvement collaborative leaders (n = 8); and focus group discussions (FGDs) with mothers-in-law (n = 4) and collaborative members (n = 7). Multivariable logistic regression was used to examine the association of network and community norms with facility birth. Thematic analysis of the qualitative data was conducted to explain this relationship. RESULTS: The network norm of perceived family approval of facility delivery (AOR: 5.54, CI: 1.65-18.57) and the community norm of perceived number of women in the community that deliver in a facility (AOR: 3.00, CI: 1.66-5.43) were independently associated with facility delivery. In qualitative IDIs and FGDs both norms were also collectively perceived as influencing facility delivery. However, network norms were more influential in women's utilization of facility-based pregnancy-related care. Healthcare improvement collaboratives were important in swaying both network and community norms toward facility-based delivery by offering pregnancy-related health information, antenatal care, and support for facility delivery. CONCLUSION: Quality improvement initiatives impact both community and network norms. To be most impactful in advancing facility-based pregnancy-related care, these initiatives should focus on highlighting the shifting trend toward facility delivery in rural communicates and promoting support for facility delivery among women's personal networks.

Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents.

Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper.

Effects of Acute and Repeated Dose Toxicity Profiling of Chelidonic Acid in Rats: in Silico and in Vivo Evidence.

Chelidonic acid is a phytoconstituent found in rhizomes of the perennial plant celandine. The current study aims to evaluate the acute and repeated dose oral toxicity study of chelidonic acid as per the OECD guidelines 425 and 407. The pharmacokinetic and toxicity profile of chelidonic acid was predicted using online servers and tools. A single dose of chelidonic acid (2000 mg/kg) was administered to female Wistar rats in an acute toxicity study, and the animals were monitored for 14 days. We studied the toxicity profile of chelidonic acid at 10, 20, and 40 mg/kg doses in Wistar rats for repeated dose toxicity (28 days). Clinical biochemistry, haematological, and urine parameters were estimated. A gross necropsy and histopathology were performed. A single oral dose of chelidonic acid (2000 mg/kg) showed no signs of toxicity or mortality. The Administration of chelidonic acid showed no significant alterations in haematological, biochemical, and urine parameters. The histopathology showed normal structure and architecture in all the vital organs. A gross necropsy of vital organs showed no signs of toxicity. The chelidonic acid was found to be safe at all selected dose levels in the acute and repeated dose toxicity study in rats.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Formulation development and evaluation of therapeutic contact lens loaded with ganciclovir.

PURPOSE: In the present investigation ganciclovir (GAN) loaded microparticles dispersed in hydrogel-based contact lenses were fabricated, characterized and evaluated for eye irritation. METHODS: GAN-Hydroxy Propyl Methyl Cellulose (HPMC) microparticles were prepared by solvent evaporation method and evaluated for entrapment efficiency, drug content and drug release. The Polyhydroxyethylmethacrylate (pHEMA) contact lenses were synthesized by free radical polymerization reaction using crosslinkers like ethylene glycoldimethacrylate and photoinitiator such as IRGACURE 1173®, in UVB light, λ 365 nm. The GAN-HPMC microparticles when incorporated into the premonomer mixture and polymerized together give rise to a particle dispersion system in the hydrogel contact lenses. The contact lenses were studied for surface morphology, transmittance, swelling, drug release, Na+ion permeability and hens egg test chorioallantoic membrane assay (HETCAM). RESULTS: Hydrogel contact lens exhibited satisfactory surface morphology, transmittance, swelling, Na+ion permeability (3.72 × 106 mm2/min) and a release of 48 h suggesting a potential for prolonged ocular drug delivery. Furthermore, HETCAM exhibited no signs of ocular irritation. CONCLUSION: The developed delivery platform is a promising alternative to conventional dosage forms like eye drops, suspensions and ointments due to its increase in the residence time attributed to its prolonged release profile.

Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI.

Brainstem nuclei play a pivotal role in many functions, such as arousal and motor control. Nevertheless, the connectivity of arousal and motor brainstem nuclei is understudied in living humans due to the limited sensitivity and spatial resolution of conventional imaging, and to the lack of atlases of these deep tiny regions of the brain. For a holistic comprehension of sleep, arousal and associated motor processes, we investigated in 20 healthy subjects the resting-state functional connectivity of 18 arousal and motor brainstem nuclei in living humans. To do so, we used high spatial-resolution 7 Tesla resting-state fMRI, as well as a recently developed in-vivo probabilistic atlas of these nuclei in stereotactic space. Further, we verified the translatability of our brainstem connectome approach to conventional (e.g. 3 Tesla) fMRI. Arousal brainstem nuclei displayed high interconnectivity, as well as connectivity to the thalamus, hypothalamus, basal forebrain and frontal cortex, in line with animal studies and as expected for arousal regions. Motor brainstem nuclei showed expected connectivity to the cerebellum, basal ganglia and motor cortex, as well as high interconnectivity. Comparison of 3 Tesla to 7 Tesla connectivity results indicated good translatability of our brainstem connectome approach to conventional fMRI, especially for cortical and subcortical (non-brainstem) targets and to a lesser extent for brainstem targets. The functional connectome of 18 arousal and motor brainstem nuclei with the rest of the brain might provide a better understanding of arousal, sleep and accompanying motor functions in living humans in health and disease.