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1.
Curr Sports Med Rep ; 23(8): 277-279, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39102581

ABSTRACT

ABSTRACT: As physical therapists and exercise professionals, we have an obligation to promote health and well-being through participation in sport and recreational/physical activity. We play an active role in facilitating and encouraging movement for a large percentage of the population, including our transgender patients/clients. It is integral that we include transgender individuals in supportive and inclusive atmospheres of play, and it is critical for us to lead the conversation around the inclusion of the transgender community in recreational activities and sport. This commentary provides evidence for the physical therapy community to support, advocate for, and include all populations as we promote healthy habits through sport.


Subject(s)
Fear , Sports , Transgender Persons , Humans , Transgender Persons/psychology , Female , Male , Athletes/psychology , Health Promotion
2.
JAMA Health Forum ; 5(8): e241925, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39120893

ABSTRACT

This Viewpoint details the findings of a report from the National Academies of Sciences, Engineering, and Medicine on family caregiving among those in science, technology, engineering, mathematics, and medicine.


Subject(s)
Caregivers , Humans , Caregivers/psychology , United States , Academies and Institutes/organization & administration
3.
Chem Sci ; 15(32): 12827-12844, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39148791

ABSTRACT

Serine hydroxymethyltransferase (SHMT) is a key enzyme in the one-carbon metabolic pathway, utilizing the vitamin B6 derivative pyridoxal 5'-phosphate (PLP) and vitamin B9 derivative tetrahydrofolate (THF) coenzymes to produce essential biomolecules. Many types of cancer utilize SHMT in metabolic reprogramming, exposing the enzyme as a compelling target for antimetabolite chemotherapies. In pursuit of elucidating the catalytic mechanism of SHMT to aid in the design of SHMT-specific inhibitors, we have used room-temperature neutron crystallography to directly determine the protonation states in a model enzyme Thermus thermophilus SHMT (TthSHMT), which exhibits a conserved active site compared to human mitochondrial SHMT2 (hSHMT2). Here we report the analysis of TthSHMT, with PLP in the internal aldimine form and bound THF-analog, folinic acid (FA), by neutron crystallography to reveal H atom positions in the active site, including PLP and FA. We observed protonated catalytic Glu53 revealing its ability to change protonation state upon FA binding. Furthermore, we obtained X-ray structures of TthSHMT-Gly/FA, TthSHMT-l-Ser/FA, and hSHMT2-Gly/FA ternary complexes with the PLP-Gly or PLP-l-Ser external aldimines to analyze the active site configuration upon PLP reaction with an amino acid substrate and FA binding. Accurate mapping of the active site protonation states together with the structural information gained from the ternary complexes allow us to suggest an essential role of the gating loop conformational changes in the SHMT function and to propose Glu53 as the universal acid-base catalyst in both THF-independent and THF-dependent activities of SHMT.

4.
ACS Catal ; 14(15): 11498-11511, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39114092

ABSTRACT

Tryptophan indole lyase (TIL; [E.C. 4.1.99.1]) is a bacterial pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes reversible ß-elimination of indole from L-tryptophan. The mechanism of elimination of indole from L-tryptophan starts with the formation of an external aldimine of the substrate and PLP, followed by deprotonation of the α-CH of the substrate, forming a resonance-stabilized quinonoid intermediate. Proton transfer to C3 of the indole ring and carbon-carbon bond cleavage of the quinonoid intermediate provide indole and aminoacrylate bound to PLP, which then releases indole, followed by iminopyruvate. We have now determined the X-ray crystal structures of TIL complexes with (3S)-dioxindolyl-l-alanine, an inhibitor, and with substrates L-tryptophan, 7-aza-L-tryptophan, and S-ethyl-l-cysteine (SEC) in the presence of benzimidazole (BZI), an isostere of the product indole. These structures show a mixture of gem-diamine, external aldimine, quinonoid, and aminoacrylate intermediates, in both open and closed active site conformations. In the closed conformations of L-tryptophan, (3S)-dioxindolyl-l-alanine, and 7-aza-L-tryptophan complexes, hydrogen bonds form between Asp-133 with N1 of the ligand heterocyclic ring and NE2 of His-458 in the small domain of TIL. This hydrogen bond also forms in the BZI complex with the aminoacrylate intermediates formed from both L-tryptophan and SEC. The closed quinonoid complex of 7-aza-L-tryptophan shows that the azaindole ring in the closed conformation is bent out of plane of the Cß-C3 bond by about 40°, putting it in a geometry that leads toward the transition-state geometry. Thus, both conformational dynamics and substrate activation play critical roles in the reaction mechanism of the TIL.

5.
Addict Neurosci ; 112024 Jun.
Article in English | MEDLINE | ID: mdl-38957401

ABSTRACT

Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (µORs). The µOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Oprm1 expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies have revealed that multiple subpopulations of NAc neurons express Oprm1 mRNA, making it unclear which populations mediate diverse behaviors resulting from µOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels of Oprm1 of any NAc cell type. Here, we show that this population is selectively marked by expression of Chst9, a gene encoding a carbohydrate sulfotransferase. Notably, Chst9+ neurons exhibited more abundant expression of Oprm1 as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover, CHST9 mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of Chst9. The abundant expression of Oprm1 in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.

7.
Ann Fam Med ; 22(4): 294-300, 2024.
Article in English | MEDLINE | ID: mdl-39038984

ABSTRACT

PURPOSE: The COVID-19 pandemic not only exacerbated existing disparities in health care in general but likely worsened disparities in access to primary care. Our objective was to quantify the nationwide decrease in primary care visits and increase in telehealth utilization during the pandemic and explore whether certain groups of patients were disproportionately affected. METHODS: We used a geographically diverse primary care electronic health record data set to examine the following 3 outcomes: (1) change in total visit volume, (2) change in in-person visit volume, and (3) the telehealth conversion ratio defined as the number of pandemic telehealth visits divided by the total number of prepandemic visits. We assessed whether these outcomes were associated with patient characteristics including age, gender, race, ethnicity, comorbidities, rurality, and area-level social deprivation. RESULTS: Our primary sample included 1,652,871 patients from 408 practices. During the pandemic we observed decreases of 7% and 17% in total and in-person visit volume and a 10% telehealth conversion ratio. The greatest decreases in visit volume were observed among pediatric patients (-24%), Asian patients (-11%), and those with more comorbidities (-9%). Telehealth usage was greatest among Hispanic or Latino patients (17%) and those living in urban areas (12%). CONCLUSIONS: Decreases in primary care visit volume were partially offset by increasing telehealth use for all patients during the COVID-19 pandemic, but the magnitude of these changes varied significantly across all patient characteristics. These variations have implications not only for the long-term consequences of the COVID-19 pandemic, but also for planners seeking to ready the primary care delivery system for any future systematic disruptions.


Subject(s)
COVID-19 , Primary Health Care , SARS-CoV-2 , Telemedicine , Humans , COVID-19/epidemiology , Telemedicine/statistics & numerical data , Primary Health Care/statistics & numerical data , Female , Male , Adult , Middle Aged , Adolescent , Aged , Child , Child, Preschool , Young Adult , Infant , United States , Pandemics , Healthcare Disparities/statistics & numerical data , Healthcare Disparities/ethnology , Health Services Accessibility/statistics & numerical data , Electronic Health Records/statistics & numerical data , Infant, Newborn
8.
Ann Fam Med ; 22(4): 279-287, 2024.
Article in English | MEDLINE | ID: mdl-39038980

ABSTRACT

PURPOSE: COVID-19 is a condition that can lead to other chronic conditions. These conditions are frequently diagnosed in the primary care setting. We used a novel primary care registry to quantify the burden of post-COVID conditions among adult patients with a COVID-19 diagnosis across the United States. METHODS: We used the American Family Cohort, a national primary care registry, to identify study patients. After propensity score matching, we assessed the prevalence of 17 condition categories individually and cumulatively, comparing patients having COVID-19 in 2020-2021 with (1) historical control patients having influenza-like illness in 2018 and (2) contemporaneous control patients seen for wellness or preventive visits in 2020-2021. RESULTS: We identified 28,215 patients with a COVID-19 diagnosis and 235,953 historical control patients with influenza-like illness. The COVID-19 group had higher prevalences of breathing difficulties (4.2% vs 1.9%), type 2 diabetes (12.0% vs 10.2%), fatigue (3.9% vs 2.2%), and sleep disturbances (3.5% vs 2.4%). There were no differences, however, in the postdiagnosis monthly trend in cumulative morbidity between the COVID-19 patients (trend = 0.026; 95% CI, 0.025-0.027) and the patients with influenza-like illness (trend = 0.026; 95% CI, 0.023-0.027). Relative to contemporaneous wellness control patients, COVID-19 patients had higher prevalences of breathing difficulties and type 2 diabetes. CONCLUSIONS: Our findings show a moderate burden of post-COVID conditions in primary care, including breathing difficulties, fatigue, and sleep disturbances. Based on clinical registry data, the prevalence of post-COVID conditions in primary care practices is lower than that reported in subspecialty and hospital settings.


Subject(s)
COVID-19 , Influenza, Human , Primary Health Care , Registries , SARS-CoV-2 , Humans , COVID-19/epidemiology , Male , Female , United States/epidemiology , Primary Health Care/statistics & numerical data , Middle Aged , Influenza, Human/epidemiology , Adult , Aged , Prevalence , Chronic Disease/epidemiology
9.
bioRxiv ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38948801

ABSTRACT

Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early gene Fos in Reln+ neurons after cocaine experience, and also revealed enrichment of Reln mRNA in Drd1 + medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selective Reln knockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss of Reln prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.

10.
J Am Med Inform Assoc ; 31(8): 1754-1762, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38894620

ABSTRACT

OBJECTIVE: To identify impacts of different survey methodologies assessing primary care physicians' (PCPs') experiences with electronic health records (EHRs), we compared three surveys: the 2022 Continuous Certification Questionnaire (CCQ) from the American Board of Family Medicine, the 2022 University of California San Francisco (UCSF) Physician Health IT Survey, and the 2021 National Electronic Health Records Survey (NEHRS). MATERIALS AND METHODS: We evaluated differences between survey pairs using Rao-Scott corrected chi-square tests, which account for weighting. RESULTS: CCQ received 3991 responses from PCPs (100% response rate), UCSF received 1375 (3.6% response rate), and NEHRS received 858 (18.2% response rate). Substantial, statistically significant differences in demographics were detected across the surveys. CCQ respondents were younger and more likely to work in a health system; NEHRS respondents were more likely to work in private practice; and UCSF respondents disproportionately practiced in larger academic settings. Many EHR experience indicators were similar between CCQ and NEHRS, but CCQ respondents reported higher documentation burden. DISCUSSION: The UCSF approach is unlikely to supply reliable data. Significant demographic differences between CCQ and NEHRS raise response bias concerns, and while there were similarities in some reported EHR experiences, there were important, significant differences. CONCLUSION: Federal EHR policy monitoring and maintenance require reliable data. This test of existing and alternative sources suggest that diversified data sources are necessary to understand physicians' experiences with EHRs and interoperability. Comprehensive surveys administered by specialty boards have the potential to contribute to these efforts, since they are likely to be free of response bias.


Subject(s)
Electronic Health Records , Physicians, Primary Care , Humans , Male , Female , Surveys and Questionnaires , Middle Aged , Adult , United States , Attitude of Health Personnel , Bias , Health Care Surveys
11.
bioRxiv ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38712125

ABSTRACT

The lateral septum (LS) is a midline, subcortical structure, which regulates social behaviors that are frequently impaired in neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Mouse studies have identified neuronal populations within the LS that express a variety of molecular markers, including vasopressin receptor, oxytocin receptor, and corticotropin releasing hormone receptor, that control specific facets of social behavior. Despite its critical role in the regulation of social behavior and notable gene expression patterns, comprehensive molecular profiling of the human LS has not been performed. Here, we conducted single nucleus RNA-sequencing (snRNA-seq) to generate the first transcriptomic profiles of the human LS using postmortem human brain tissue samples from 3 neurotypical donors. Our analysis identified 4 transcriptionally distinct neuronal cell types within the human LS that are enriched for TRPC4, the gene encoding Trp-related protein 4. Differential expression analysis revealed a distinct LS neuronal cell type that is enriched for OPRM1, the gene encoding the µ-opioid receptor. Leveraging recently collected mouse LS snRNA-seq datasets, we also conducted a cross-species analysis. Our results demonstrate that TRPC4 enrichment in the LS is highly conserved between human and mouse, while FREM2, which encodes FRAS1 related extracellular matrix protein 2, is enriched only in the human LS. Together, these results highlight transcriptional heterogeneity of the human LS, and identify robust marker genes for the human LS.

13.
JAMA Health Forum ; 5(5): e240913, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38758567

ABSTRACT

This case series identifies states' estimates of primary care spending and recommends steps policymakers can take toward standardizing these estimates.


Subject(s)
Health Expenditures , Primary Health Care , Primary Health Care/economics , United States , Humans
14.
Sex Transm Dis ; 51(7): 456-459, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38602774

ABSTRACT

BACKGROUND: In the United States, most chlamydia cases are reported from non-sexually transmitted disease clinics, and there is limited information focusing on the reasons for chlamydia testing in private settings. These analyses describe clinical visits to primary care providers where chlamydia testing was performed to help discern between screening and diagnostic testing for chlamydia. METHODS: Using the largest primary care clinical registry in the United States, the PRIME registry, chlamydia tests were identified using Current Procedural Terminology procedure codes and categorized as diagnostic testing for sexually transmitted infection (STI)-related symptoms, screening for chlamydia, or "other," based on Classification of Diseases, Tenth Revision Evaluation and Management codes selected for visits. RESULTS: Of 120,013 clinical visits with chlamydia testing between January 1, 2019, and December 31, 2022, 70.4% were women; 20.6% were with STI-related symptoms, 59.9% were for screening, and 19.5% for "other" reasons. Of those 120,013 clinical visits with chlamydia testing, the logit model showed that patients were significantly more likely to have STI-related symptoms if they were female than male, non-Hispanic Black than non-Hispanic White, aged 15 to 24 years than aged ≥45 years, and resided in the South than in the Northeast. CONCLUSION: It is important to know what proportion of chlamydial infections is identified through screening programs and to have this information stratified by demographics. The inclusion of laboratory results could further facilitate a better understanding of the impact of chlamydia screening programs on the identification and treatment of chlamydia in private office settings in the United States.


Subject(s)
Chlamydia Infections , Mass Screening , Primary Health Care , Humans , Female , United States , Male , Chlamydia Infections/diagnosis , Adult , Adolescent , Young Adult , Middle Aged , Registries
15.
EClinicalMedicine ; 72: 102604, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38680517

ABSTRACT

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.

18.
JAMA Netw Open ; 7(3): e243793, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38530309

ABSTRACT

Importance: Enabling widespread interoperability-the ability of health information technology systems to exchange information and to use that information without special effort-is a primary focus of public policy on health information technology. More information on clinicians' experience using that technology can serve as one measure of the impact of that policy. Objective: To assess primary care physician perspectives on the state of interoperability. Design, Setting, and Participants: A cross-sectional survey of family medicine physicians in the US was conducted from December 12, 2021, to October 12, 2022. A sample of family medicine physicians who completed the Continuous Certification Questionnaire (CCQ), a required part of the American Board of Family Medicine certification process, which has a 100% response rate, were invited to participate. Main Outcomes and Measures: Eighteen items on the CCQ assessed experience accessing and using various information from outside organizations, including medications, immunizations, and allergies. Results: A total of 2088 physicians (1053 women [50%]; age reported categorically as either ≥50 years or <50 years) completed the CCQ interoperability questions in 2022. Of these respondents, 35% practiced in hospital or health system-owned practices, while 27% practiced in independently owned practices. Eleven percent were very satisfied with their ability to electronically access all 10 types of information from outside organizations included on the questionnaire, and a mean of 70% were at least somewhat satisfied. A total of 23% of family medicine physicians reported information from outside organizations was very easy to use, and an additional 65% reported that information was somewhat easy to use. Only 8% reported that information from different electronic health record (EHR) developers' products was very easy to use compared with 38% who reported information from the same EHR developer's product was very easy to use. Conclusions and Relevance: This survey study of family medicine physicians found modest and uneven improvement in physicians' experience with interoperability. These findings suggest that substantial heterogeneity in satisfaction by information type, source of information, EHR, practice type, ownership, and patient population necessitates diverse policy and strategies to improve interoperability.


Subject(s)
Physicians, Primary Care , Humans , Female , Middle Aged , Cross-Sectional Studies , Certification , Electronic Health Records , Personal Satisfaction
20.
Nat Rev Rheumatol ; 20(3): 138, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38332243
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