Barriers and facilitators to self-care practices for sexual and reproductive health among women of reproductive age.

INTRODUCTION: Sexual and Reproductive Health and Rights (SRHR) have been promoted globally, yet sexual and reproductive health (SRH) interventions are seldom evaluated from the perspective of service users and service providers. Very little is known about whether and why various target groups including general women are (or are not) practicing SRH -related self-care practices. This study explored SRH self-care practices and facilitators and barriers to the adoption of SRH self-care among reproductive-age women of Nepal. METHODS: In this descriptive qualitative study, we conducted in-depth interviews in June 2022 with ten married women of reproductive age (service users) and four SRHR service providers (program managers and health service providers) in Nepal. Thematic analysis was conducted for data analysis. RESULTS: We found that commonly practiced self-care practices were self-administration of contraceptives, self-management of pain, self-monitoring of pregnancy, self-awareness and seeking medical abortions (tele-abortion), self-medication for pre-exposure prophylaxis for HIV, and self-testing for HIV and pregnancy. The multi-level barriers to SRH self-care were poor knowledge and perceived lack of need for SRH self-care, limited access, and negative behaviors from the service providers. The program-related barriers included lack of evidence, limited financial resources, lack of accountability, and limited knowledge and skills among service providers on SRH self-care measures. Peer support, an increasing number of service sites, and access to and use of digital (health) tools emerged as the facilitators of SRH self-care. CONCLUSIONS: The findings of this study suggest that addressing barriers such as poor knowledge, limited access, and negative attitudes while leveraging facilitators such as peer support and digital tools is essential for promoting and enabling effective SRH self-care among women. Population-wide awareness programs supplemented by increasing service sites are essential for increasing SRH self-care practices.

Experience of a single academic institution with the National Accreditation Program for Rectal Cancer and the resulting improvement in care.

AIM: The American College of Surgeons Committee on Cancer developed the National Accreditation Program for Rectal Cancer (NAPRC) to reduce variations in rectal cancer care, standardize clinical practice and encourage multidisciplinary approaches. The aim of this study was to analyse if accreditation achieved a higher quality of care at one hospital. METHOD: The University of California Davis Medical Center was accredited in 2019. A retrospective review of rectal adenocarcinoma patients was performed between the years 2013 and 2018. Patients presenting from 2013 to 2015 were discussed at a gastrointestinal tumour board while patients in 2018 had an accredited rectal cancer tumour board. Patients from 2016 to 2017 were excluded as the programme was still developing. Compliance to the NAPRC standards was compared between the cohorts. RESULTS: One hundred and thirty patients were evaluated, 88 (68%) in the prerectal tumour board cohort and 42 (32%) in the rectal tumour board cohort. The prerectal tumour board cohort often failed to meet attendance standards. All patients in the rectal tumour board cohort met all criteria. Similarly, clinical service compliance improved in the rectal tumour board cohort for 13 metrics, 10 of which were statistically significant. Although a high proportion of patients in both groups experienced quality surgery, i.e. complete total mesorectal excision and negative margins, the lack of complete pathological reporting in the prerectal tumour board cohort limited analysis. CONCLUSION: Multidisciplinary rectal cancer tumour boards are associated with improved compliance with recommended care by the NAPRC. Patients discussed at a rectal cancer tumour board were more likely to receive appropriate staging, coordinated care and have better clinical documentation.

The long weight: association between distressed communities index and long-term weight outcomes following bariatric surgery.

BACKGROUND: Socioeconomic status (SES) is multifactorial, and its effect on post-bariatric weight recurrence is unclear. Distressed Community Index (DCI) is a composite SES score measuring community economic well-being. This study aims to evaluate the effect of DCI on long-term post-bariatric weight outcomes. METHODS: Retrospective analysis of patients undergoing primary laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy between 2015 and 2020 was performed. All weights in the electronic medical record (EMR), including non-bariatric visits, were captured. Patients were stratified into low tier (LT) and high tier (HT) DCI groups. RESULTS: Of 583 patients, 431 (73.9%) were HT and 152 (26.1%) were LT. Average bariatric follow up was 1.78 ± 1.6 years and average postoperative weight in the EMR was 3.96 ± 2.26 years. Rates of bariatric follow up within the last year were similar (13.8% LT vs 16.2% HT, p = 0.47). LT had higher percent total body weight loss (%TWL; 26% LT vs 23% HT, p < 0.01) and percent excess weight loss (%EWL; 62% vs 57%, p = 0.04) at 1 year on univariate analysis. On multivariate linear regression adjusting for baseline characteristics and surgery type, there were no differences in %EWL between groups at 1 year (p = 0.22), ≥ 3 years (p = 0.53) or ≥ 5 years (p = 0.34) postop. While on univariate analysis LT only trended towards greater percentage of patients with > 15% increase from their 1-year weight (33.3% LT vs 21.0% HT, p = 0.06), on multivariate analysis this difference was significant (OR 2.0, LT 95%CI 1.41-2.84). There were no differences in the percentage of patients with > 15% decrease in %EWL from 1 to 3 + years postop between groups (OR 0.98, LT 95% CI 0.72-1.35). CONCLUSIONS: While low tier patients had similar weight loss at 1 year, they were twice as likely to have weight recurrence at ≥ 3 years. Further studies are needed to identify factors contributing to greater weight recurrence among this population.

Hepatic Macrophage Types Cluster with Disease Etiology in Chronic Liver Disease and Differ Compared to Normal Liver: Implications for Their Biologic and Diagnostic Role.

Introduction. Macrophages are phenotypically heterogeneous cells that play a vital role in hepatic fibrogenesis. We aimed to compare the macrophage profiles between normal livers and those with various chronic liver diseases in the precirrhotic fibrosis stage. Methods. Immunohistochemistry was performed for three macrophage markers (CD163, CD68, and IBA1) on 48 liver biopsies. Digital image analysis and automated cell count were used to calculate the densities of immunostained cells in two selected regions of interest: the periportal region and the perivenous region. Results. The absolute and relative densities of the macrophage phenotypes in relationship with zones and etiologies showed four distinct patterns by hierarchical cluster analysis: (1) no significant increase in the macrophage densities in either periportal or perivenous regions - nonalcoholic steatohepatitis; (2) significant increase in the selected macrophage densities in both periportal and perivenous regions - Hepatitis C; (3) significant increase in the macrophage densities only in periportal region - alcoholic liver disease, primary sclerosing cholangitis, and primary biliary cholangitis; and (4) significant increase in the densities of all types of macrophages in both periportal and perivenous regions - autoimmune hepatitis. Conclusions. There are distinct macrophage phenotypic and zonal geographic signatures correlating to etiologies of chronic liver disease in the precirrhotic stage.

Exploring Motor Neuron Diseases Using iPSC Platforms.

The degeneration of motor neurons is a pathological hallmark of motor neuron diseases (MNDs), but emerging evidence suggests that neuronal vulnerability extends well beyond this cell subtype. The ability to assess motor function in the clinic is limited to physical examination, electrophysiological measures, and tissue-based or neuroimaging techniques which lack the resolution to accurately assess neuronal dysfunction as the disease progresses. Spinal muscular atrophy (SMA), spinal and bulbar muscular atrophy (SBMA), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS) are all MNDs with devastating clinical outcomes that contribute significantly to disease burden as patients are no longer able to carry out normal activities of daily living. The critical need to accurately assess the cause and progression of motor neuron dysfunction, especially in the early stages of those diseases, has motivated the use of human iPSC-derived motor neurons (hiPSC-MN) to study the neurobiological mechanisms underlying disease pathogenesis and to generate platforms for therapeutic discovery and testing. As our understanding of MNDs has grown, so too has our need to develop more complex in vitro models which include hiPSC-MN co-cultured with relevant non-neuronal cells in 2D as well as in 3D organoid and spheroid systems. These more complex hiPSC-derived culture systems have led to the implementation of new technologies, including microfluidics, multielectrode array, and machine learning which offer novel insights into the functional correlates of these emerging model systems.

Establishment of an Electrophysiological Platform for Modeling ALS with Regionally-Specific Human Pluripotent Stem Cell-Derived Astrocytes and Neurons.

Human pluripotent stem cell-derived astrocytes (hiPSC-A) and neurons (hiPSC-N) provide a powerful tool for modeling Amyotrophic Lateral Sclerosis (ALS) pathophysiology in vitro. Multi-electrode array (MEA) recordings are a means to record electrical field potentials from large populations of neurons and analyze network activity over time. It was previously demonstrated that the presence of hiPSC-A that are differentiated using techniques to promote a spinal cord astrocyte phenotype improved maturation and electrophysiological activity of regionally specific spinal cord hiPSC-motor neurons (MN) when compared to those cultured without hiPSC-A or in the presence of rodent astrocytes. Described here is a method to co-culture spinal cord hiPSC-A with hiPSC-MN and record electrophysiological activity using MEA recordings. While the differentiation protocols described here are particular to astrocytes and neurons that are regionally specific to the spinal cord, the co-culturing platform can be applied to astrocytes and neurons differentiated with techniques specific to other fates, including cortical hiPSC-A and hiPSC-N. These protocols aim to provide an electrophysiological assay to inform about glia-neuron interactions and provide a platform for testing drugs with therapeutic potential in ALS.

Elderly Age Is Associated With More Conservative Treatment of Invasive Melanoma.

BACKGROUND/AIM: Competing mortality risks complicate treatment of elderly melanoma patients potentially leading to conservative management, including no sentinel lymph node biopsy. As systemic immunotherapy offers justification for nodal evaluation, we examined treatment trends among elderly melanoma patients. PATIENTS AND METHODS: We performed a National Cancer Database analysis of melanoma patients from 2004-2015. Patients were categorized by age (elderly ≥80-years-old). Multivariable logistic regression analyses were performed comparing characteristics and treatment by age. RESULTS: Of 187,814 patients, 2.7% were 1-25, 11.6% were 26-40, 46.6% were 41-64, 28.8% were 65-79, and 10.3% were ≥80-years-old with clinicopathologic and treatment differences between age cohorts. Nodal surgery was least common among elderly patients (43.1% vs. 60.7-69.8%, p<0.0001). For stage III, immunotherapy was least common among the elderly (p<0.0001), but associated with greater survival (HR=0.52, 95%CI=0.32-0.84, p=0.008). CONCLUSION: Elderly melanoma patients were often treated conservatively, including no nodal evaluation, concerning for the potential undertreatment of this population.

Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia.

The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.