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Background Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. Methods Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case–control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. Results A total of 75 studies met the inclusion criteria for systematic review. Among the case–control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. Conclusion Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

We developed this web based ‘Dysmetabolism-Risk Calculator’ after analysing 1800 individuals, who underwent ‘standard two hour 75 gram OGTT’ along with insulin levels. It calculates the basal and post-glucose indexes of insulin secretion (ISec), insulin resistance (IRes) and beta cell function (BCF), based on areas under the curve of both glucose (AUCg) and insulin (AUCi). It generates dynamic graphs of glucose and insulin along with population-norm values and determines various stages of dys-insulinemia, obesity, and diabetes. On the dysmetabolism time-line, ‘Euglycemic Hyperinsulinemia’ and ‘Midzone Hyperglycemia’, are specially important categories. These categories, characteristically, occur before ‘Prediabetes’ stage, (Pre-Prediabetes), and are known to be associated with increased cardio-vascular morbidity such as hypertension, dyslipidemia, endothelial dysfunction, and stroke. IRes is calculated using “AUCg*AUCi*k” formula. ISec and central IRes is calculated by measuring ‘rate of rise of insulin’ and the angle theta, which is subtended by the 30 min insulin curve with ‘x’ axis. Insulin disposal and peripheral IRes is determined by calculating angle zeta which is subtended by the 90-120 min insulin curve with ‘y’ axis. Disposition index (Isec*Ires*k) is calculated by the formula “1/(AUCg) 2”, which, noticeably, is independent of AUCi. The discordance between Insulin Secretion Index and OGTT Disposition Index will be useful in predicting the reversibility of diabetes and dysmetabolism. BMI, 0-30 & 90-120 min AUCis are used as parameters, while calculating the probable site of ‘Tissue IRes’. Cardio-Vascular risk calculations are based on hyperinsulinemia (as macrovascular risk), hyperglycemia (as microvascular risk), and their combination as they occur on dysmetabolism time-time.

Socioeconomic and racial disparities exist in access to care among patients with non-small cell lung cancer (NSCLC) in the United States. Immunotherapy is a widely established treatment modality for patients with advanced-stage NSCLC (aNSCLC). We examined associations of area-level socioeconomic status with receipt of immunotherapy for aNSCLC patients by race/ethnicity and cancer facility type (academic and non-academic). We used the National Cancer Database (2015–2016), and included patients aged 40–89 years who were diagnosed with stage III-IV NSCLC. Area-level income was defined as the median household income in the patient’s zip code, and area-level education was defined as the proportion of adults aged ≥ 25 years in the patient’s zip code without a high school degree. We calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) using multi-level multivariable logistic regression. Among 100,298 aNSCLC patients, lower area-level education and income were associated with lower odds of immunotherapy treatment (education: aOR 0.71; 95% CI 0.65, 0.76 and income: aOR 0.71; 95% CI 0.66, 0.77). These associations persisted for NH-White patients. However, among NH-Black patients, we only observed an association with lower education (aOR 0.74; 95% CI 0.57, 0.97). Across all cancer facility types, lower education and income were associated with lower immunotherapy receipt among NH-White patients. However, among NH-Black patients, this association only persisted with education for patients treated at non-academic facilities (aOR 0.70; 95% CI 0.49, 0.99). In conclusion, aNSCLC patients residing in areas of lower educational and economic wealth were less likely to receive immunotherapy.

The role of RORγ as a transcription factor for Th17 cell differentiation and thereby regulation of IL-17 levels is well known. Increased RORγ expression along with IL-17A levels was observed in animal models, immune cells and BAL fluid of COPD patients. Increased IL-17A levels in severe COPD patients are positively correlated with decreased lung functions and increased severity symptoms and emphysema, supporting an urgency to develop novel therapies modulating IL-17 or RORγ for COPD treatment. We identified a potent RORγ inhibitor, PCCR-1 using hit to lead identification followed by extensive lead optimization by structure–activity relationship. PCCR-1 resulted in RORγ inhibition with a high degree of specificity in a biochemical assay, with > 300-fold selectivity over other isoforms of ROR. Our data suggest promising potency for IL-17A inhibition in human and canine PBMCs and mouse splenocytes with no significant impact on Th1 and Th2 cytokines. In vivo, PCCR-1 exhibited significant efficacy in the acute CS model with dose-dependent inhibition of the PD biomarkers that correlated well with the drug concentration in lung and BAL fluid, demonstrating an acceptable safety profile. This inhibitor effectively inhibited IL-17A release in whole blood and BALf samples from COPD patients. Overall, we identified a selective inhibitor of RORγ to pursue further development of novel scaffolds for COPD treatment.

The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2 3 factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320–498 nm, and the EE was between 32.89 and 56.56 %. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery.

Early childhood caries (ECC) is an aggressive form of dental caries occurring in the first five years of life. Despite its prevalence and consequences, little progress has been made in its prevention and even less is known about individuals’ susceptibility or genomic risk factors. The genome-wide association study (GWAS) of ECC (“ZOE 2.0”) is a community-based, multi-ethnic, cross-sectional, genetic epidemiologic study seeking to address this knowledge gap. This paper describes the study’s design, the cohort’s demographic profile, data domains, and key oral health outcomes. Between 2016 and 2019, the study enrolled 8059 3–5-year-old children attending public preschools in North Carolina, United States. Participants resided in 86 of the state’s 100 counties and racial/ethnic minorities predominated—for example, 48% (n = 3872) were African American, 22% white, and 20% (n = 1611) were Hispanic/Latino. Seventy-nine percent (n = 6404) of participants underwent clinical dental examinations yielding ECC outcome measures—ECC (defined at the established caries lesion threshold) prevalence was 54% and the mean number of decayed, missing, filled surfaces due to caries was eight. Nearly all (98%) examined children provided sufficient DNA from saliva for genotyping. The cohort’s community-based nature and rich data offer excellent opportunities for addressing important clinical, epidemiologic, and biological questions in early childhood.

Purpose The disruption of undergraduate medical education (UME) by the COVID-19 pandemic has sparked rapid, real-time adjustments by medical educators and students. While much is known about online teaching in general, little guidance is available to medical educators on how to adapt courses not originally designed for the online environment. To guide our faculty in this transition we conducted a needs assessment of students enrolled in virtual courses across all 4 years of UME training. Methods Using a mixed-methods approach, we conducted a single-institution virtual learning needs assessment in May and June of 2020. We developed and disseminated a survey to assess student experiences with virtual learning. We conducted quantitative and qualitative analysis of responses ( n  = 255 or 39%) to identify emergent themes. Results We identified six interdependent themes that need to be met for medical students to fully reach their learning potential: access to stable internet and quiet study spaces, flexible course design with asynchronous, self-paced components, clear expectations for engagement with content and each other, a sense of connectedness with faculty and peers, synchronous classes that maximize interactivity, and assessments that foster a sense of learning over performance. Interpersonal relationships with faculty and peers affected students’ sense of learning more than any other factor. Conclusions Based on our findings we propose a hierarchy of needs for virtual learning that provides guidance on adapting existing medical school courses to the remote setting and overcoming common challenges. We highlight opportunities for how virtual elements may enrich in-person courses going forward, including in the clinical setting. Although the solutions required to meet the threshold of need at each level may differ based on the context, attending to these same fundamental needs can be extrapolated and applied to learners across a range of environments beyond the virtual.

Background and Aim Some studies have found a positive association between irritable bowel syndrome (IBS) and metabolic syndrome; however, none are from India. Methods We conducted a cross‐sectional study of 1040 adults aged between 18 and 50 years. Individuals from the annual health check‐up setting were screened using anthropometry and biochemistry. Based on the results, they were identified as with and without metabolic syndrome. We excluded individuals who were already diagnosed with metabolic syndrome or those who were already on medication for diabetes mellitus or hypertension or dyslipidemia. All the participants were administered the Rome III questionnaire for the diagnosis of IBS. Results Metabolic syndrome was found in 307 of 1040 (29.5%) while 33 of 1040 (3.2%) had IBS. The proportion of IBS was not significantly different between participants with and without metabolic syndrome (1.6% vs 3.8% respectively; P = 0.06). Those with IBS had significantly greater mean weight (72.4 vs 67.2 kg; P = 0.009), mean waist circumference (88.8 vs 85.2 cm; P = 0.011), mean body mass index (BMI) (26.2 vs 24.2 kg/m2; P = 0.002), and higher mean fasting glucose (96 vs 89 mg/dL; P < 0.000) respectively. Conclusion The prevalence of metabolic syndrome and IBS are comparable to previous literature from India. There was no association between metabolic syndrome and IBS. The proportion of irritable bowel syndrome (IBS) was not significantly different between participants with and without metabolic syndrome. We found higher mean waist circumference and fasting glucose values and lower mean HDLC values in participants with IBS. The mean weight and mean BMI values were also found to be significantly higher in the IBS group.

IntroductionLess than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions—Availability, Affordability, Accessibility, Accommodation and Acceptability—among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to OC disparities.Methods and analysisWe will use the Surveillance Epidemiology and Ends Results dataset linked with Medicare claims data from 9744 patients with OC ages 65 years and older. We will recruit 1641 patients with OC (413 black, 299 Hispanic and 929 white) from cancer registries in nine US states. We will examine HCA dimensions in relation to three main outcomes: (1) receipt of quality, guideline adherent initial treatment and supportive care, (2) quality of life based on patient-reported outcomes and (3) survival. We will obtain saliva and vaginal microbiome samples to examine prognostic biomarkers. We will use hierarchical regression models to estimate the impact of HCA dimensions across patient, neighbourhood, provider and hospital levels, with random effects to account for clustering. Multilevel structural equation models will estimate the total, direct and indirect effects of race on treatment mediated through HCA dimensions.Ethics and disseminationResult dissemination will occur through presentations at national meetings and in collaboration with collaborators, community partners and colleagues across othercancer centres. We will disclose findings to key stakeholders, including scientists, providers and community members. This study has been approved by the Duke Institutional Review Board (Pro00101872). Safety considerations include protection of patient privacy. All disseminated data will be deidentified and summarised.