3-Amino-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carbonitrile: A fluorescent molecule that induces differentiation in PC12 cells.

Neural differentiation is triggered by the activation of multiple signaling pathways initiated by various neurotrophic factors. An elucidation of these mechanisms is anticipated to facilitate the prevention of diseases and the development of novel therapeutic approaches. Alternative small-molecule inducers for neuroscience studies are required instead of protein-based reagents for more efficient and convenient experiments. We demonstrated that small molecules of thieno[2,3-b]pyridine derivatives that induce neural differentiation, compounds 3a and 9a in particular, exhibited significant neuritogenic activity in rat pheochromocytoma (PC12) cells. Moreover, 3a displayed pronounced fluorescence and a discernible Stokes shift. Furthermore, the outcome of the experiment conducted on the NGF-insensitive clones of rat PC12 cells, and the results of the intercellular uptake analyses suggested that the 3a-mediated activation of neural differentiation occurred independently of the TrkA receptor. Therefore, 3a portrays potential applicability both as a small molecule reagent to replace novel neurotrophic factors and as a potent fluorescent reagent for various techniques, including bioimaging.

Chronic Cough: Evaluation and Management.

Chronic cough is a cough lasting longer than 8 weeks in adults and 4 weeks in children. In the United States, more than 12.3 million individuals are estimated to have chronic cough. The most common causes of chronic cough in adults are upper airway cough syndrome, asthma, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and laryngopharyngeal reflux. The initial assessment of chronic cough should include cost-effective diagnostic tests, such as chest radiography and spirometry, and empiric and targeted treatment for the most common etiologies. An assessment of medications (e.g., angiotensin-converting enzyme inhibitors), environment, occupation, and potential chemical triggers should be conducted. For chronic refractory cough, physiotherapy and speech and language therapy combined with a trial of gabapentin or amitriptyline can be considered. When initial test findings are unremarkable, further diagnostic tests, such as bronchoscopy and nasendoscopy, are often warranted through referral to a pulmonologist and otolaryngologist. Common etiologies in children include protracted bacterial bronchitis, asthma, bronchiectasis, upper airway cough syndrome, and gastroesophageal reflux disease. Because of the high likelihood of spontaneous resolution, children with a dry cough without wheezing or exertional dyspnea may be observed for 2 weeks.

Virtual community outreach during the COVID-19 pandemic: addressing health disparities for vulnerable populations.

Context: COVID-19 has worsened health disparities among vulnerable populations, including minority and non-English-speaking populations. Community outreach is an effective method to bridge the gap for those populations. Virtual Community Outreach (VCO) emerged as a novel and sustainable approach during the pandemic but is unstudied. Objective: 1) Evaluate the effectiveness and usefulness of VCO. 2) Assess impact on patient health literacy. Study Design: Prospective cohort study at a single site. Dataset: Anonymous survey data collected after each virtual community outreach meeting, May 2020-May 2021 (No July meeting). Excluded data from September 2020 meetings due to inconsistent survey questions. Population studied: Members of an email list commonly subscribed by Japanese in Pittsburgh. Only one survey accepted if multiple family members attended the meetings via one registration. Intervention: Virtual weekend meetings held monthly for two hours. Lectures provided by healthcare professionals about requested topics from previous participants, including how to schedule a healthcare appointment, COVID-19 vaccines, health maintenance in the pandemic. Outcome Measures: age group, gender, length of stay in community, satisfaction level and usefulness of VCO, self-assessed impact on health literacy, patient at our clinic or not, intention to establish care at our clinic. Results: Average attendance 12.6 families per meeting. Survey response rate: 86.2% (119/139). Respondent demographics: Female 71.1% (81/114), Age group 40-49 years old, 38.1% (43/113), followed by 30-39 years old 35.4% (40/113), Length of stay in Pittsburgh (median) 5 years. Satisfaction level with virtual outreach meeting "very satisfied" or "satisfied" 98.3% (117/119). Usefulness of virtual outreach meeting "very useful" or "useful" 96.6% (115/119). Among participants who received care at our clinic, 70.3% (45/64) reported VCO improved their health literacy, including their decision whether to seek care when symptomatic. Among participants who had never been to our clinic 81.3% (39/48) expressed intention to establish care with us. Conclusions: VCO can be a novel and useful method to improve health literacy for those with vulnerability during the COVID-19 pandemic. VCO also may expand primary care access to that population, as attendees meet clinicians through virtual lectures and learn about the clinic. Also, through VCO, the clinic can reach and recruit diverse patients.

Improving lipophilicity of 5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid increases its efficacy to activate hypoxia-inducible factors.

Hypoxia-inducible factor (HIF) activators aid the treatment of renal anemia and ischemia. Recently, PyrzA (5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid), a HIF activator by PHD inhibition without a 2-oxoglutarate moiety was reported. However, PyrzA has low lipophilicity, and it was necessary to improve its solubility by synthesizing derivatives. In this study, we synthesized and evaluated a higher lipophilic derivative of PyrzA and found that it exhibited higher HIF activity and stabilizing ability at low concentrations compared to Roxadustat, a commercially available HIF activator.

Communication sheet eases barriers for Japanese patients and health professionals.

BACKGROUND: Language and cultural barriers can affect healthcare outcomes of minority populations. However, limited data are available on communication tools developed to address health disparities resulting from language and cultural barriers. Our study aimed to reduce communication barriers between Japanese patients and non-Japanese-speaking clinic staff by developing a Japanese-English Communication Sheet (JECS) to create more equitable clinical environments for Japanese patients in ambulatory care. METHODS: This study was conducted at a family health center in a United States urban setting, in the city of Pittsburgh, between November 2019 and August 2020. This study included Japanese adult patients who had health care office visits with one of two Japanese-speaking physicians and who completed a survey about the JECS. The JECS, written in Japanese and English, targets common sources of confusion by presenting common health questions, written in Japanese, and by explaining differences between common healthcare processes in Japan and the United States. Clinic staff who used the JECS with Japanese-speaking patients also were surveyed about the tool. RESULTS: Sixty Japanese patients met inclusion criteria and completed the survey. More than half of participants found the JECS useful, and those with self-reported limited English proficiency were most likely to report that the JECS was useful (p = 0.02). All nine non-Japanese speaking staff surveyed found the sheet helpful. CONCLUSIONS: The JECS is a useful communication tool for addressing common barriers faced by Japanese patients seeking care at an American health center where Japanese-speaking physicians work but no clinic staff speak Japanese. A focused communication sheet can facilitate communication between patients and clinic staff and also reduce health inequities resulting from linguistic and cultural barriers. Additionally, using a communication sheet can advance quality and safety of patient care at the individual and institutional level.

Impact of flexible hexyl chain ordering in a mononuclear spin crossover iron(III) complex.

A novel FeIII complex [Fe(Hex-tnal)2]BPh4 (1) with a tridentate N2O ligand having an n-hexyl chain, Hex-Htnal (=1-((((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)imino)methyl)naphthalen-2-ol), is reported. Temperature-dependent magnetic susceptibility measurements revealed that 1 exhibits a two-step spin crossover (SCO) transition in the 400-10 K temperature range, including an unusual gradual χMT change above RT (300-345 K) and a hysteretic χMT jump in a narrow temperature range of 345-357 K. These behaviors were also characterized by differential scanning calorimetry. Variable-temperature single-crystal X-ray diffraction studies revealed that the order-disorder transition and conformational change of the hexyl chains and the symmetry change associated with the re-entrant structural phase transition, namely triclinic P1̄ (100-275 K) ↔ monoclinic C2/c (296-340 K) ↔ triclinic P1̄ (360 K), are coupled to variations in intermolecular interactions and the N4O2 coordination environment, resulting in the occurrence of the unusual two-step SCO transition of 1. This study demonstrates that the flexible motion of alkyl substituents in the supramolecular lattice influences the occurrence of anomalous magnetic switching properties.

HIV Pre-Exposure Prophylaxis Education in Family Medicine Clerkships: A CERA Study.

BACKGROUND AND OBJECTIVES: Little is known about human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) education in family medicine clerkships during medical school. Our study aimed to describe coverage of PrEP education in family medicine clerkships and explore barriers if this education was absent. METHODS: Data were collected through the 2023 Council of Academic Family Medicine (CAFM) Education Research Alliance (CERA) Family Medicine Clerkship Director Survey. We inquired about provision of PrEP to patients, faculty expertise with PrEP, PrEP curriculum in the clerkship, barriers to including PrEP in the clerkship curriculum, and willingness of directors to add PrEP online modules to the clerkship if available. RESULTS: The response rate was 56.8% (96/169). Nine participants did not complete the PrEP questions and were excluded from analyses. Nearly two-thirds of clerkship directors perceived PrEP as an important topic in the family medicine clerkship; however, only one-third of clerkships included PrEP curriculum through clinical experiences (58.5%), didactics (17.1%), or both (14.6%). Barriers to including PrEP were lack of time in the curriculum (63.5%) and having other more important topics to cover (25.7%), but 38.9% said they would include PrEP in the clerkship if free online modules were available. CONCLUSIONS: Clerkships were more likely to include PrEP curriculum in the family medicine clerkship if they had faculty with sufficient expertise or if clerkship directors believed it was important to teach PrEP in the curriculum. Offering accessible educational content can enhance educational opportunities on PrEP for medical students.

Strategies and Barriers for Diversity, Equity, Inclusion, and Antiracism Work in Family Medicine Departments: A CERA Study.

BACKGROUND AND OBJECTIVES: Medical schools and family medicine organizations have been working on advancing diversity, equity, inclusion, and antiracism (DEIA). Black, Indigenous, and People of Color (BIPOC) faculty members are disproportionately expected to lead DEIA initiatives, negatively affecting academic promotion and well-being. Our study aimed to describe the existing DEIA initiatives, strategies, and barriers to implementing support for DEIA work, as well as the implications of addressing the minority tax in US and Canadian family medicine departments. METHODS: We used data collected as a part of the 2023 Council of Academic Family Medicine Educational Research Alliance (CERA) study. The survey was delivered to 227 department chairs across the United States and Canada. RESULTS: The survey response rate was 50.2% (114/227). Sixty-two percent of the respondents strongly agreed that advancing DEIA was important, and 55.4% reported having a DEIA leader, with 75.4% of those positions reportedly held by BIPOC faculty. Lack of funding was identified as the most significant barrier (26.2%), followed by lack of faculty expertise (18.7%). Department chairs who strongly agreed that DEIA work was important were significantly more likely to report having a DEIA committee, mentorship for BIPOC faculty, and a holistic review for faculty recruitment than those who did not strongly agree. CONCLUSIONS: Though most department chairs perceived advancing DEIA work as important, appropriate compensation and institutional support are often lacking. Further study is needed to explore ways in which departments can enhance their institutional support for DEIA initiatives.

Colorectal Cancer Screening Among Individuals With a Substance Use Disorder: A Retrospective Cohort Study.

Introduction: There is limited evidence on colorectal cancer screening among individuals with a substance use disorder. This study aims to investigate the association between personal history of a substance use disorder and colorectal cancer colonoscopy screening completion rates. Methods: This retrospective cohort study analyzed 176,300 patients, of whom 171,973 had no substance use disorder and 4,327 had a substance use disorder diagnosis from electronic health record data (January 1, 2008-December 31, 2022) in a Midwestern healthcare system. Baseline was January 1, 2013, and a 10-year follow-up period ran through December 31, 2022. The outcome was receipt of colonoscopy in the 10-year follow-up period. Patients were aged 50-65 years at baseline, meaning that they were eligible for a colonoscopy through the entirety of the 10-year follow-up period. Covariates included demographics (age, race, and neighborhood SES), health services utilization, psychiatric and physical comorbidities, and prior colonoscopy or fecal occult blood testing. Entropy balancing was used to control for confounding in weighted log-binomial models calculating RR and 95% CIs. Results: Patients were on average aged 57.1 (±4.5) years, 58.2% were female, 81.0% were White, and 16.9% were of Black race. The most prevalent comorbidities were obesity (29.6%) and hypertension (29.4%), followed by smoking/nicotine dependence (21.0%). The most prevalent psychiatric comorbidity was depression (6.4%), followed by anxiety disorder (4.5%). During the 10-year follow-up period, 40.3% of eligible patients completed a colorectal cancer colonoscopy screening test, and individuals with a substance use disorder diagnosis were significantly less likely to receive a colorectal cancer colonoscopy screening test both prior to and after controlling for confounding (RR=0.73; 95% CI=0.70, 0.77 and RR=0.81; 95% CI=0.74, 0.89, respectively). Results were not modified by sex, race, psychiatric comorbidity, or neighborhood SES. Conclusions: Personal history of substance use disorder was independently associated with lower screening completion rates. Healthcare professionals should recognize unique barriers among individuals with substance use disorder and then address them individually as a multidisciplinary team in the outpatient setting to reduce this health disparity.