Eco-friendly Approaches to Chromene Derivatives: A Comprehensive Review of Green Synthesis Strategies.

Synthetic routes of chromene are an area of thrust research due to its wide application as pigments, agrochemicals, cosmetics, and an important nucleus scaffold for various pharmaco-logically active drugs. The chromene nucleus is an important moiety for the discovery of new drug candidates owing to its broad range of pharmacological actions like antitumor, anti-inflammatory, antiviral, and many others. However, traditional synthesis techniques frequently use unsafe reagents and produce hazardous waste, presenting environmental issues. The eco-friendly production of chromene derivatives utilizes sustainable raw materials, non-toxic cata-lysts, and gentle reaction conditions to reduce ecological consequences. Innovative methods like microwave irradiation, ultrasound synthesis, the use of environmentally friendly solvents, a cata-lyst-based approach with minimal environmental impact, and mechanochemistry-mediated syn-thesis are implemented. These approaches provide benefits in scalability, cost-effectiveness, and ease of purification. This review compiles and presents various recently reported green synthetic strategies of chromene and its derivatives and gives the reader a clear idea of the detailed and crit-ical aspects of various synthetic protocols described.

Understanding social risk factors in patients presenting to the emergency Department for Acute Heart Failure: A pilot study.

BACKGROUND: The standard of care for congestive heart failure (CHF) aims to slow disease progression and maximize patient function, however there is an increase in emergency department (ED) revisits and readmissions. Social risk factors play a role in the disease management and prognosis of CHF. There is a gap in the identification of low-risk CHF patient who would be safely discharged using an initial social risk factor stratification. OBJECTIVES: To generate a social risk profile for patients presenting to the ED with acute CHF exacerbation and identify variables that may increase the risk of 7-day and overall mortality, 30-day ED revisit, and readmission. METHODS: We conducted a pilot prospective survey-based study among adult patients presenting to the ED with acute CHF exacerbation. The combination of a self-report questionnaire and retrospective chart review was used to generate a CHF risk profile. RESULTS: A total of 62 patients were recruited in the pilot study with a mean age of 69.5 years. The preliminary data indicated that prior to this ED visit, 21% of patients were not aware of a previous CHF diagnosis; 64.5% of patients rated their sleep quality as poor or very poor; 72.6% reported orthopnea; and 43.5% reported recent weight gain. 37.1% of patients did not adhere to dietary recommendations and some patients did not adhere to their medication regime 100%. CONCLUSION: This study suggests establishing a social risk profile for patients presenting to the ED with CHF can help formulate a CHF-specific care plan and optimize multidisciplinary management to reduce ED revisits and readmissions.

Cadherin Expression Is Regulated by Mechanical Phenotypes of Fibroblasts in the Perivascular Matrix.

INTRODUCTION: The influence of mechanical forces generated by stromal cells in the perivascular matrix is thought to be a key regulator in controlling blood vessel growth. Cadherins are mechanosensors that facilitate and maintain cell-cell interactions and blood vessel integrity, but little is known about how stromal cells regulate cadherin signaling in the vasculature. Our objective was to investigate the relationship between mechanical phenotypes of stromal cells with cadherin expression in 3D tissue engineering models of vascular growth. METHODS: Stromal cell lines were subjected to a bead displacement assay to track matrix distortions and characterize mechanical phenotypes in 3D microtissue models. These cells included human ventricular cardiac (NHCF), dermal (NHDF), lung (NHLF), breast cancer-associated (CAF), and normal breast fibroblasts (NBF). Cells were embedded in a fibrin matrix (10 mg/mL) with fluorescent tracker beads; images were collected every 30 min. We also studied endothelial cells (ECs) in co-culture with mechanically active or inactive stromal cells and quantified N-Cad, OB-Cad, and VE-Cad expression using immunofluorescence. RESULTS: Bead displacement studies identified mechanically active stromal cells (CAFs, NHCFs, NHDFs) that generate matrix distortions and mechanically inactive cells (NHLFs, NBFs). CAFs, NHCFs, and NHDFs displaced the matrix with an average magnitude of 3.17 ± 0.11 µm, 3.13 ± 0.06 µm, and 2.76 ± 0.05 µm, respectively, while NHLFs and NBFs displaced the matrix with an average of 1.82 ± 0.05 µm and 2.66 ± 0.06 µm in fibrin gels. Compared to ECs only, CAFs + ECs as well as NBFs + ECs in 3D co-culture significantly decreased expression of VE-Cad; in addition, Pearson's Correlation Coefficient for N-Cad and VE-Cad showed a strong correlation (>0.7), suggesting cadherin colocalization. Using a microtissue model, we demonstrated that mechanical phenotypes associated with increased matrix deformations correspond to enhanced angiogenic growth. The results could suggest a mechanism to control tight junction regulation in developing vascular beds for tissue engineering scaffolds or understanding vascular growth during developmental processes. CONCLUSION: Our studies provide novel data for how mechanical phenotype of stromal cells in combination with secreted factor profiles is related to cadherin regulation, localization, and vascularization potential in 3D microtissue models.

Contemporary experience of mitral transcatheter edge-to-edge repair technology in patients with mitral annular calcification.

BACKGROUND: Mitral annular calcification (MAC) has been an exclusion for many of the earlier pivotal trials that were instrumental in gaining device approval and indications for mitral transcatheter edge-to-edge repair (M-TEER). AIMS: To evaluate the impact of MAC on the procedural durability and success of newer generation MitraClip® systems (G3 and G4 systems). METHODS: Data were collected from Northwell TEER registry. Patients that underwent M-TEER with third or fourth generation MitraClip device were included. Patients were divided into -MAC (none-mild) and +MAC (moderate-severe) groups. Procedural success was defined as ≤ grade 2 + mitral regurgitation (MR) postprocedure, and durability was defined as ≤ grade 2 + MR retention at 1 month and 1 year. Univariate analysis compared outcomes between groups. RESULTS: Of 260 M-TEER patients, 160 were -MAC and 100 were +MAC. Procedural success was comparable; however, there were three patients who required conversion to cardiac surgery during the index hospitalization in the +MAC group versus none in the -MAC group (though this was not statistically significant). At 1-month follow-up, there were no significant differences in MR severity. At 1-year follow-up, +MAC had higher moderate-severe MR (22.1% vs. 7.5%; p = 0.002) and higher mean transmitral gradients (5.3 vs. 4.0 mmHg; p = 0.001) with no differences in mortality, New York Heart Association functional class or ejection fraction. CONCLUSION: In selective patients with high burden of MAC, contemporary M-TEER is safe, and procedural success is similar to patients with none-mild MAC. However, a loss of procedural durability was seen in +MAC group at 1-year follow-up. Further studies with longer follow-ups are required to assess newer mTEER devices and their potential clinical implications in patients with a high burden of MAC.

Ensuring fidelity: key elements to consider in disseminating a diabetes telemanagement program for underserved Hispanic/Latinos living with type 2 diabetes.

Background: The Hispanic/Latino population has greater risk (estimated >50%) of developing type 2 diabetes (T2D) and developing it at a younger age. The American Diabetes Association estimates costs of diagnosed diabetes in 2017 was $327 billion; with medical costs 2.3x higher than patients without diabetes. The purpose of this manuscript is to describe the methodology utilized in a randomized controlled trial aimed at evaluating the efficacy of a diabetes telemanagement (DTM) program for Hispanic/Latino patients with T2D. The intent is to provide information for future investigators to ensure that this study can be accurately replicated. Methods: This study was a randomized controlled trial with 240 participants. Eligible patients (Hispanic/Latino, aged 18+, living with T2D) were randomized to Comprehensive Outpatient Management (COM) or DTM. DTM was comprised of usual care, including routine clinic visits every three months, as well as: Biometrics (a tablet, blood glucose meter, blood pressure monitor, and scale); Weekly Video Visits (facilitated in the patient's preferred language); and Educational Videos (including culturally congruent diabetes self-management education and quizzes). COM consisted of usual care including routine clinic visits every three months. For this study, COM patients received a glucometer, glucose test strips, and lancets. Establishing a therapeutic nurse-patient relationship was a fundamental component of our study for both groups. First contact (post-enrollment) centered on ensuring that patients and caregivers understood the program, building trust and rapport, creating a non-judgmental environment, determining language preference, and establishing scheduling availability (including evenings and weekends). DTM were provided with a tablet which allowed for self-paced education through videos and weekly video visits. The research team and Community Advisory Board identified appropriate educational video content, which was incorporated in diabetes educational topics. Video visits allowed us to assess patient involvement, motivation, and nonverbal communication. Communicating in Spanish, and awareness of diverse Hispanic/Latino backgrounds was critical, as using relevant and commonly-used terms can increase adherence and improve outcomes. Shared decision-making was encouraged to make realistic health care choices. Conclusion: Key elements discussed above provide a framework for future dissemination of an evidence-based DTM intervention to meet the needs of underserved Hispanic/Latino people living with T2D.

A Review on the Development of Novel Heterocycles as α-Glucosidase Inhibitors for the Treatment of Type-2 Diabetes Mellitus.

One of the most effective therapeutic decencies in the treatment of Type 2 Diabetes Mellitus is the inhibition of α-glucosidase enzyme, which is present at the brush border of the intestine and plays an important role in carbohydrate digestion to form mono-, di-, and polysaccharides. Acarbose, Voglibose, Miglitol, and Erniglitate have been well-known α-glucosidase inhibitors in science since 1990. However, the long synthetic route and side effects of these inhibitors forced the researchers to move their focus to innovate simple and small heterocyclic scaffolds that work as excellent α-glucosidase inhibitors. Moreover, they are also effective against the postprandial hyperglycemic condition in Type 2 Diabetes Mellitus. In this aspect, this review summarizes recent progress in the discovery and development of heterocyclic molecules that have been appraised to show outstanding inhibition of α-glucosidase to yield positive effects against diabetes.

Importance of basic life support training in rural India.

Basic life support (BLS) provided right away can lower fatality rates. Cardiac arrest typically results in death within minutes if it is untreated. Therefore, it is of interest to assess how BLS training affected villagers. The pre-experimental one-group pre-test post-test design was chosen for the investigation. A non-probability volunteer sampling technique was adopted to collect a sample of 220 village residents who met the inclusion requirements. The participants received training in basic life support that is achieved by using a real-life role model, hands-on CPR instruction. Checklist served as a standardized method for assessing the BLS training program. The pre-test and post-test's means were 23.05 and 56.51, respectively, and their respective standard deviations were 11.89 and 8.27. The 'z test' calculation result is 12.36) The results showed that BLS training was more successful for villagers and that they required regular BLS training programs to maintain their BLS skill level.

Neurally Adjusted Ventilatory Assist Versus Pressure Support Ventilation: A Comprehensive Review.

Mechanical ventilation serves as crucial life support for critically ill patients. Although it is life-saving prolonged ventilation carries risks and complications like barotrauma, Ventilator-associated pneumonia, sepsis, and many others. Optimizing patient-ventilator interactions and facilitating early weaning is necessary for improved intensive care unit (ICU) outcomes. Traditionally Pressure support ventilation (PSV) mode is widely used for weaning patients who are intubated and mechanically ventilated. Neurally adjusted ventilatory assist (NAVA) mode of the ventilator is an emerging ventilator mode that delivers pressure depending on the patient's respiratory drive, which in turn prevents over-inflation and improves the patient's ventilator interactions. Our article revises and compares the effectiveness of NAVA compared to PSV ventilation under different contexts. Overall we conclude that NAVA level of ventilation can be safely administered in a patient with acute respiratory failure, provided diaphragmatic paralysis is not considered. NAVA improves asynchrony index, wean-off time, and sleep quality and is associated with increased ventilator-free days. These results are based on small-scale studies with low power, and further studies are warranted in large-scale cohorts with more diverse populations to confirm these results.

Experiences and recommendations from people with spinal cord injury following participation in a disability education session at an allopathic medical school: a qualitative study.

BACKGROUND: Students in half of US medical schools do not receive formal instruction in providing medical care for people with disabilities. To address this gap in training, our medical school developed several strategies, including a session for second year medical students to address communication skills, knowledge, and attitudes relevant to delivering healthcare for people with disabilities. Here, our objective was to explore perceptions of people with spinal cord injury (SCI) who participated in the session on its content and structure. METHODS: Qualitative research using a focus group of people with SCI who participated in an educational session for medical students in an LCME accredited allopathic US medical school. A purposive sample of adults with SCI (N = 8) participated in a focus group. Data were analyzed using a six-phase thematic analysis. RESULTS: Participants favorably viewed the educational session, felt their participation was valuable, and had suggestions for its improvement. Four major themes were identified: (1) session format, content; (2) addressing student discomfort and avoidance behaviors; (3) increasing student knowledge and preparation; and (4): important lessons from discussions of past and role-played doctor-patient interactions. CONCLUSIONS: First-person input from people with SCI is critical to improve medical education and healthcare provision to the SCI community. To our knowledge, this is the first study to report feedback from stakeholders providing specific recommendations for teaching disabilities awareness to undergraduate medical students. We expect these recommendations to be relevant to the SCI and medical education communities in improving healthcare for people with SCI and other disabilities.

Neoplastic Progression of Barrett's Esophagus Among Organ Transplant Recipients: a Retrospective Cohort Study.

BACKGROUND: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression. METHODS: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted. RESULTS: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients. CONCLUSION: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.

Randomized intervention to assess the effectiveness of an educational video on organ donation intent among Hispanics in the New York metropolitan area.

BACKGROUND: The Hispanic community has a high demand for organ donation but a shortage of donors. Studies investigating factors that could promote or hinder organ donation have examined emotional video interventions. Factors acting as barriers to organ donation registration have been classified as: (1) Bodily integrity; (2) medical mistrust; (3) "ick"-feelings of disgust towards organ donation; and (4) "jinx"-fear that registration may result in one dying due to premeditated plans. We predict that by providing necessary information and education about the donation process via a short video, individuals will be more willing to register as organ donors. AIM: To determine perceptions and attitudes regarding barriers and facilitators to organ donation intention among Hispanic residents in the New York metro politan area. METHODS: This study was approved by the Institutional Review Board at Northwell Health. The approval reference number is No. 19-0009 (as presented in Supplementary material). Eligible participants included Hispanic New York City (NYC) residents, 18 years of age and above, who were recruited voluntarily through Cloud Research and participated in a larger randomized survey study of NYC residents. The survey an 85-item Redcap survey measured participant demographics, attitudes, and knowledge of organ donation as well as the intention to register as an organ donor. Attention checks were implemented throughout the survey, and responses were excluded for those who did fail. Participants were randomly assigned two-between subject conditions: To view a short video on organ donation and then proceed to complete the survey (i.e., video first) and view the same video at the end of the survey (video last). No intra-group activities were conducted. This study utilized an evidenced-based emotive educational intervention (video) which was previously utilized and was shown to increase organ donation registration rates at the Ohio Department of Motor Vehicles. Results were analyzed using Jamovi statistical software. Three hundred sixty-five Hispanic individuals were included in the analysis. Once consent was obtained and participants entered the survey (the survey sample is presented in Supplementary material), participants were asked to report on demographic variables and their general impression of organ donation after death. The video depicted stories regarding organ donation after death from various viewpoints, including from the loved ones of a deceased person who died waiting for a transplant; from the loved ones of a deceased person whose organs were donated upon death; and, from those who were currently waiting for a transplant. RESULTS: Using a binomial logistic regression, the analysis provides information about the relationship between the effects of an emotive video and the intention to donate among Hispanic participants who were not already registered as donors. The willingness to go back and register was found to be significantly more probable for those who watched the emotive video before being asked about their organ donation opinions (odds ratio: 2.05, 95% confidence interval: 1.06-3.97). Motivations for participation in organ donation were also captured with many stating the importance of messages coming from "people like me" and a message that highlights "the welfare of those in need". Overall, the findings suggest that using an emotive video that addresses organ donation barriers to prompt organ donation intentions can be effective among the Hispanic populous. Future studies should explore using targeted messaging that resonates with specific cultural groups, highlighting the welfare of others. CONCLUSION: This study suggests that an emotive educational intervention is likely to be effective in improving organ donation registration intent among the Hispanic population residing in NYC.

COVID-19 stressors for Hispanic/Latino patients living with type 2 diabetes: a qualitative study.

Background and aim: During the early stages of the COVID-19 pandemic, nationwide lockdowns caused disruption in the diets, physical activities, and lifestyles of patients with type 2 diabetes. Previous reports on the possible association between race/ethnicity, COVID-19, and mortality have shown that Hispanic/Latino patients with type 2 diabetes who are socioeconomically disadvantaged are disproportionately affected by this novel virus. The aim of this study was to explore stressors associated with changes in diabetes self-management behaviors. Our goal was to highlight the health disparities in these vulnerable racial/ethnic minority communities and underscore the need for effective interventions. Methods and participants: Participants were enrolled in part of a larger randomized controlled trial to compare diabetes telehealth management (DTM) with comprehensive outpatient management (COM) in terms of critical patient-centered outcomes among Hispanic/Latino patients with type 2 diabetes. We conducted a thematic analysis using patient notes collected from two research nurses between March 2020 and March 2021. Two authors read through the transcripts independently to identify overarching themes. Once the themes had been identified, both authors convened to compare themes and ensure that similar themes were identified within the transcripts. Any discrepancies were discussed by the larger study team until a consensus was reached. Results: Six themes emerged, each of which can be categorized as either a source or an outcome of stress. Sources of stress associated with the COVID-19 pandemic were (1) fear of contracting COVID-19, (2) disruptions from lockdowns, and (3) financial stressors (e.g., loss of income). Outcomes of COVID-19 stressors were (1) reduced diabetes management (e.g., reduced diabetes monitoring and physical activity), (2) suboptimal mental health outcomes (e.g., anxiety and depression), and (3) outcomes of financial stressors. Conclusion: The findings indicated that underserved Hispanic/Latino patients with type 2 diabetes encountered a number of stressors that led to the deterioration of diabetes self-management behaviors during the pandemic.

Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study.

BACKGROUND: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma. METHODS: In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria). FINDINGS: We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM). INTERPRETATION: Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies. FUNDING: SU2C Dream Team and Cancer Research UK.

Black Physicians' Experiences with Anti-Black Racism in Healthcare Systems Explored Through An Attraction-Selection-Attrition Lens.

Anti-Black racism is a specific form of racism directed at Black people. In healthcare, there are poignant examples of anti-Black racism in the recruitment, selection, and retention stages of the job cycle. Research shows that anti-Black racism is associated with inequitable work outcomes and the under-representation of Black physicians. However, empirical findings are scattered with no organizing framework to consolidate these findings. To add to the literature, in this paper we present the attraction-selection-attrition (ASA) model (Schneider, 1987) as an organizing framework to discuss Black physicians' experiences with anti-Black racism and discrimination throughout their careers. We draw from previous literature to highlight specific experiences of Black physicians at each stage of the job cycle (i.e., attraction, selection, retention), and we offer considerations on how practitioners can mitigate anti-Black racism throughout the job cycle. In the wake of COVID-19 and highly publicized social justice movements, healthcare systems are seeking ways to increase the recruitment, selection, and retention of Black physicians to ensure health equity. We believe this guide will be valuable to practitioners, leaders, researchers, and program directions seeking to advance diversity, equity, and inclusion of Black physicians in their healthcare systems. We conclude by providing practical implications and directions for future research.

Cannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum Stress.

Introduction: The aggregation of misfolded proteins in the endoplasmic reticulum (ER) is a pathological trait shared by many neurodegenerative disorders. This aggregation leads to the persistent activation of the unfolded protein response (UPR) and ultimately apoptosis as a result of ER stress. Cannabidiol (CBD) has been demonstrated to be neuroprotective in various cellular and animal models of neurodegeneration, which has been attributed to its antioxidant and anti-inflammatory properties. However, little is known about the role of CBD in the context of protein folding and ER stress. The purpose of this study was to investigate whether CBD is neuroprotective against an in vitro model of ER stress. Materials and Methods: Using different exposure models, mouse striatal STHdhQ7/Q7 cells were exposed to either the ER stress inducer thapsigargin (TG) and/or CBD. Cell viabilities assays were used to investigate the effect of CBD pre-treatment, co-treatment, and post-treatment on TG-induced cell death. Real-time quantitative polymerase chain reaction was used to measure changes in ER stress regulators and UPR genes such as glucose-regulated protein-78 (GRP78), mesencephalic astrocyte-derived neurotrophic factor (MANF), B cell lymphoma 2 (BCL-2), BCL-2 interacting mediator of cell death (BIM), and caspase-12. Results: Cell viability increased significantly when cells were pre-treated with CBD before TG exposure. An increase in the gene expression of pro-survival ER chaperone GRP78 and ER-resident neurotrophic factor MANF coincided with this effect and decreased ER-mediated pro-apoptotic markers such as BIM, and caspase-12 was observed. Conclusions: These data suggest that CBD pre-treatment is neuroprotective against TG-induced cell death. Understanding the role of ER stress in CBD-driven neuroprotection provides insight into the therapeutic potential of CBD and the role of ER dysfunction in neurodegenerative disorders.

Social Determinants of Health in Women With Heart Failure: Prospective Observational Cohort Study.

Objective: The social determinants of health (SDoH) account for 80%-90% of modifiable contributors to health outcomes for chronic diseases such as heart failure. Knowledge gaps exist on how SDoH influences hospitalization rates in women with heart failure. Our aim was to evaluate the relationship between the baseline SDoH status of women with heart failure with subsequent all-cause and cardiovascular hospitalization. Methods: This is a prospective observational longitudinal cohort study of women diagnosed with heart failure with 6-month follow-up. The subjects completed SDoH assessment by the Institute of Medicine. Monthly follow-ups were performed to assess for hospitalization events. Results: A total of 92 patients with at least 1 follow-up clinic visit were included. The mean age was 66 ± 15 years and 80% had nonischemic cardiomyopathy as the etiology of heart failure. New York Heart Association (NYHA) Classifications I-II were the most common (n = 66, 71.8%). In total, 51 patients (55.4%) had overall high-risk SDoH (4 or more SDoH domains at risk). By the 6-month follow-up, 22 (23.9%) patients were hospitalized for any cause; 8 patients (8.7%) were hospitalized for cardiovascular causes. There were no deaths. In multivariate logistic regression analysis, the high-risk SDoH group had a higher odds ratio for all-cause hospitalization (OR 5.31, 95% CI 1.59-17.73). In addition, Kansas City Cardiomyopathy Questionnaire 12-item (KCCQ-12) scores, surrogate for quality of life, were worse in the high-risk SDoH group. Conclusion: SDoH adversely impacts hospitalizations and quality of life in women with heart failure. Future efforts for screening and interventions should evaluate the SDoH at all levels, including the individual health care provider, institutional, and national levels.

Temporal trends and disparities in gastroenterology care use before, during, and after COVID-19 lockdown.

Socioeconomic disparities adversely affected healthcare use during COVID-19 lockdown. However, trends in these disparities post lockdown are unknown. Therefore, our aim was to study temporal trends and factors associated with gastroenterology healthcare access and disparities during and after COVID-19 lockdown. This cohort study consisted of patients receiving outpatient care in the Cleveland Clinic gastroenterology department between March 2020 and June 2020 and corresponding time periods in 2019 and 2021. Patient demographics and socioeconomic factors were extracted and analyzed. There were 47,031 patients (mean age 56.3±17.6 years, 61.9% female and 76.4% white) included. Patients ≥65 years sought healthcare less frequently during and after the lockdown (40.1% vs 34.8% vs 35.2% in 2019, 2020, and 2021 respectively). Missed visits (4.2% vs 10% vs 10.4%), tobacco (11.4% vs 15.9% vs 16.1%), alcohol (38.6% vs 45.5% vs 50.9%), and illicit drug use (3.5% vs 5.8% vs 10.7%) have steadily increased during and after the lockdown compared with prepandemic levels. Factors associated with reduced telehealth use were black race (OR 0.89, 95% CI 0.81 to 0.99), Hispanic race (OR 0.63, 95% CI 0.51 to 0.77)), Medicaid/other public insurance (OR 0.87, 95% CI 0.79 to 0.95)), unemployed status (OR 0.85, 95% CI 0.79 to 0.92)), and non-English/Spanish speakers (OR 0.66, 95% CI 0.46 to 0.94)). In conclusion, socioeconomic and ethnic disparities persist in healthcare use even a year after the onset of the COVID-19 pandemic. There is an alarming increase in missed visits and substance abuse. Therefore, efforts should be targeted on improving healthcare access for these aforementioned vulnerable groups.

Decreased Expression of Cerebral Dopamine Neurotrophic Factor in Platelets of Probable Alzheimer Patients.

BACKGROUND: Alzheimer disease (AD) patients experience progressive neurological and cognitive decline attributed to neurodegeneration. Cerebral dopamine neurotrophic factor (CDNF) has been identified to protect and rescue neurons in various preclinical neurodegeneration models. The expression of this protein occurs in both the central nervous system and peripheral blood. Blood platelets exhibit several biochemical impairments similar to the brain tissues of patients with neurological disorders. This study examines CDNF mRNA expression in human blood platelets in healthy subjects and Alzheimer-probable patients. METHODS: Platelets were extracted from whole blood from patients. mRNA was extracted to synthesize cDNA and quantify CDNF gene expression from 21 Alzheimer-probable patients and 73 healthy age-matched control subjects using real-time qPCR. Grouping analysis of the data with regard to sex was conducted. RESULTS: CDNF mRNA expression was significantly decreased in Alzheimer-probable patients relative to the control subjects (P<0.05). Further analysis demonstrated reduced CDNF expression in male Alzheimer-probable patients compared with their age and sex-matched controls (P<0.05). However, no change in female subjects was observed. Interestingly, there is a lower level of CDNF expression in the female control group relative to the control male group (P<0.05). CONCLUSION: Alzheimer-probable male patients demonstrated significant reductions in CDNF expression, suggesting that CDNF plays a significant role in the pathogenesis of AD. In addition, it may assist in diagnosing male Alzheimer patients.

Ketamine-induced neurotoxicity is mediated through endoplasmic reticulum stress in vitro in STHdhQ7/Q7 cells.

Ketamine has traditionally been used as a dissociative anesthetic agent and more recently as a treatment for treatment-resistant depression. However, there is growing concern over the increased use of ketamine in recreational and therapeutic settings due to the potential neurotoxic effects. Recent studies have demonstrated that ketamine is cytotoxic in several cell types, such as fibroblasts, hepatocytes, uroepithelial cells, and adult induced pluripotent stem cells (iPSCs). Ketamine has been shown to dysregulate calcium signalling, increase reactive oxygen species (ROS) production, and impair mitochondrial function, ultimately leading to apoptosis. However, it is unclear whether endoplasmic reticulum (ER) stress plays a role in ketamine associated neurotoxicity in striatal neurons. Disruption to ER homeostasis can initiate ER-mediated cell death, which has been implicated in several neurodegenerative diseases. Thus, the purpose of this study was to determine whether ketamine's neurotoxic effects involve an ER stress-dependent pathway and to elucidate the underlying mechanisms involved in its neurotoxic effects. Mouse striatal cells were treated with various concentrations of ketamine (10 µM, 100 µM, 1 mM) or DMEM for 9-72 hrs. Cell viability was assessed using the MTT assay, and changes in gene expression of ER stress markers were evaluated using RT-qPCR. MTT results revealed that 1 mM ketamine decreased cell viability in striatal cells after 24 h of treatment. Gene expression studies complemented these findings such that ketamine upregulated pro-apoptotic ER stress markers, including X-box binding protein 1 (XBP1), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) and downregulated pro-survival ER stress proteins such as GRP78, MANF and CDNF. Ketamine activated all three stress sensing pathways including PERK, IRE1, and ATF6. Taken together, our results show that ketamine-induced neurotoxicity is mediated through an ER stress-dependent apoptotic pathway.

Pharmacist-Physician Collaborative Practice to Improve Diabetes Care at Tampa General Medical Group.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a pharmacist-physician collaborative effort to reduce A1C and blood pressure and thereby lower risks for complications for people with diabetes being treated at a network of family care clinics in the Tampa, FL, area.