Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 1.787
Filtrer
1.
BMC Med Educ ; 24(1): 980, 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39252083

RÉSUMÉ

PURPOSE: The United States Medical Licensing Examination (USMLE) is an examination series required for allopathic physician licensure in the United States (US). USMLE content is created and maintained by the National Board of Medical Examinations (NBME). The specialty composition of the USMLE and NBME taskforce members involved in the creation of examination content is currently unknown. METHODS: Using the 2021 USMLE and 2021 NBME Committees and Task Forces documents, we determined each member's board-certified primary specialty and involvement in test material development committees who we dubbed "test writers". Total active physicians by primary specialty were recorded from the 2020 Physician Specialty Data Report published by the Association of American Medical Colleges (AAMC). Descriptive statistics and chi-square analysis were used to analyze the cohorts. RESULTS: The USMLE and NBME test writer primary specialty composition was found to be significantly different compared to the US active physician population (USMLE χ2[32] = 172, p < .001 and NBME χ2[32] = 200, p < .001). Only nineteen specialties were represented within USMLE test writers, with three specialties being proportionally represented. Two specialties were represented within NBME test writers. Obstetrics and Gynecology physicians were proportionally represented in USMLE but not within NBME test writers. Internal Medicine (IM) accounts for the largest percentage of all USMLE test writers (60/197, 30%) with an excess representation of 31 individuals. CONCLUSIONS: There is an imbalance in the specialty representation of USMLE and NBME test writers compared to the US active physician population. These findings may have implications for the unbiased and accurate portrayal of topics in such national examinations; thus, future investigation is warranted.


Sujet(s)
Évaluation des acquis scolaires , Autorisation d'exercer la médecine , Autorisation d'exercer la médecine/normes , États-Unis , Humains , Médecine , Médecins , Spécialisation
2.
PLoS Negl Trop Dis ; 18(9): e0012482, 2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39255310

RÉSUMÉ

BACKGROUND: Climate change and urbanization will alter the global distribution of disease vectors, changing the disease burden in yet unpredictable ways. Aedes aegypti is a mosquito responsible for transmitting dengue, Zika, chikungunya, and yellow fever viruses that breeds in containers associated with urban environments. We sought to understand how ambient temperature and larval densities in the immature aquatic phases determine adult life history traits and dengue virus loads post-infection. We predicted that larval crowding and high temperatures would both lead to smaller mosquitoes that might struggle to invest in an immune response and, hence, would exhibit high viral loads. METHODS: We first examined larval densities from urban and rural areas via a meta-analysis. We then used these data to inform a laboratory-based 2x2 design examining the interacting effects of temperature (21 vs. 26°C) and density (0.2 vs. 0.4 larvae/mL) on adult life history and dengue virus loads. RESULTS: We found that urban areas had an ~8-fold increase in larval densities compared to more rural sites. In the lab, we found that crowding had more impact on mosquito traits than temperature. Crowding led to slower development, smaller mosquitoes, less survival, lower fecundity, and higher viral loads, as predicted. The higher temperature led to faster development, reduced fecundity, and lower viral loads. The virus-reducing effect of higher temperature rearing was, however, overwhelmed by the impact of larval crowding when both factors were present. CONCLUSIONS: These data reveal complex interactions between the environmental effects experienced by immature mosquitoes and adult traits. They especially highlight the importance of crowding with respect to adult viral loads. Together, these data suggest that urban environments might enhance dengue virus loads and, therefore, possibly transmission, a concerning result given the increasing rates of urbanization globally.

4.
medRxiv ; 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39108502

RÉSUMÉ

Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 of these individuals. Principal component analysis (PCA) on the clinical markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results: 221 unique CpGs reached genome-wide significance at timepoint 1 (T1) after Bonferroni correction. PC7 accounted for the majority of associations (204), which correlated with loadings of eosinophil counts and immunoglobulin levels. Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint (T2) identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points (271 in total) yielded a correlation of 0.81. Conclusion: We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to using this robust DNA methylation profile as a new, stable biomarker for asthma.

5.
bioRxiv ; 2024 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-39091873

RÉSUMÉ

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

6.
mSystems ; : e0054524, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39191377

RÉSUMÉ

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection. IMPORTANCE: Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.

7.
J Patient Saf ; 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39194332

RÉSUMÉ

BACKGROUND: Emergency and urgent care settings face challenges with routinely obtaining performance feedback related to diagnostic care. Patients and their care partners provide an important perspective on the diagnostic process and outcome of care in these settings. We sought to develop and test psychometric properties of Patient-Report to IMprove Diagnostic Excellence in Emergency Department settings (PRIME-ED), a measure of patient-reported diagnostic excellence in these care settings. METHODS: We developed PRIME-ED based on literature review, expert feedback, and cognitive testing. To assess psychometric properties, we surveyed AmeriSpeak, a probability-based panel that provides sample coverage of approximately 97% of the U.S. household population, in February 2022 to adult patients, or their care partners, who had presented to an emergency department or urgent care facility within the last 30 days. Respondents rated their agreement on a 5-point Likert scale with each of 17 statements across multiple domains of patient-reported diagnostic excellence. Demographics, visit characteristics, and a subset of the Emergency Department Consumer Assessment of Healthcare Providers & Systems were also collected. We conducted psychometric testing for reliability and validity. RESULTS: Over a thousand (n = 1116) national panelists completed the PRIME-ED survey, of which 58.7% were patients and 40.9% were care partners; 49.6% received care at an emergency department and 49.9% at an urgent care facility. Responses had high internal consistency within 3 patient-reported diagnostic excellence domain groupings: diagnostic process (Cronbach's alpha 0.94), accuracy of diagnosis (0.93), and communication of diagnosis (0.94). Domain groupings were significantly correlated with concurrent Emergency Department Consumer Assessment of Healthcare Providers & Systems items. Factor analyses substantiated 3 domain groupings. CONCLUSIONS: PRIME-ED has potential as a tool for capturing patient-reported diagnostic excellence in emergency and urgent care.

8.
J Phys Chem A ; 128(36): 7609-7619, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39213596

RÉSUMÉ

Advancements in photocatalysis have transformed synthetic organic chemistry, using light as a powerful tool to drive selective chemical transformations. Recent approaches have focused on metal-halide ligand-to-metal charge transfer (LMCT) photoactivated bond homolysis reactions leveraged by earth-abundant elements to generate valuable synthons for radical-mediated cross-coupling reactions. Of recent utility, oxovanadium(V) LMCT photocatalysts exhibit selective alkoxy radical generation from aliphatic alcohols upon blue light (UVA) irradiation under mild conditions. The selective photochemical liberation of alkoxy radicals is valuable for applying late-stage fragmentation approaches in organic synthesis and depolymerization strategies for nonbiodegradable polymers. Steady-state and time-resolved spectroscopy were used to assign the electronic structure of three well-defined V(V) photocatalysts in their ground and excited states. We assign the excited state for this transformation at earth-abundant vanadium(V), interrogating the electronic structure using static UV-visible absorption, ultrafast transient absorption, and electron paramagnetic resonance spectroscopy coupled to computational approaches. These findings afford assignments of the short-lived excited state intermediates that dictate selective homolytic bond cleavage in metal alkoxides, illustrating the valuable insight gleaned from fundamental investigations of the molecular photochemistry responsible for light-escalated chemical transformations.

9.
J Electr Bioimpedance ; 15(1): 89-98, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-39105154

RÉSUMÉ

Advances in wearable technologies now allow modern smartwatches to collect body composition estimates through bioelectrical impedance techniques embedded within their design. However, this technique is susceptible to increased measurement error when postural changes alter body fluid distribution. The purpose of this study was to evaluate the effects of postural orientation on body composition and total body water (TBW) estimates produced by smartwatch bioelectrical impedance analysis (SWBIA) and determine its agreement with criterion measures. For this cross-sectional evaluation, 117 (age: 21.4±3.0 y; BMI: 25.3±5.7 kg/m2) participants (F:69, M:48) completed SWBIA measurements while in the seated, standing, and supine positions, then underwent criterion dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance spectroscopy (BIS) assessments. In the combined sample and females, body fat percent, fat mass, and fat-free mass using SWBIA were significantly different between the supine and standing positions (all p<0.001), though group level agreement with DXA was similar across positions. Supine SWBIA TBW estimates were significantly different between seated and standing estimates (all p≤0.026), but further analyses revealed that this was driven by the supine and seated differences observed in females (p=0.003). SWBIA TBW demonstrated similar group and individual level agreement with BIS across body positions with slight improvements observed during seated and supine assessments for females and males, respectively. SWBIA may demonstrate slight intra- and inter-device differences in body composition and TBW when measured across postural orientations, though further evaluations in external/clinical samples are necessary. While sex/position-specific guidelines may improve precision, these findings highlight the importance of standardized body positioning when using SWBIA.

10.
J Hosp Med ; 2024 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-39164921

RÉSUMÉ

BACKGROUND: Diagnostic errors are a leading cause of patient harm. In 2022, the Leapfrog Group published a report containing 29 evidence-based practices that hospitals can adopt to reduce diagnostic errors. OBJECTIVES: To understand the extent to which US hospitals have already implemented these practices, we conducted a national pilot survey of Leapfrog-participating hospitals. METHODS: To reduce respondent burden, we divided the 29 practices across two surveys: one focused on organizational culture and structure (Domain 1), and the second focused on the diagnostic process itself (Domain 2). RESULTS: A total of 95 hospitals from 23 states responded to one or both surveys. On average, hospitals reported implementing 9 of the 16 practices (56%) in Domain 1 and 8 of the 13 practices (62%) in Domain 2. The rate of practice implementation varied greatly, with some hospitals implementing as few as three practices in their domain. The most commonly implemented practices were ensuring access to medical interpreters, continuous access to radiologists, ensuring staff and patients can report diagnostic errors and concerns, and having a formal process to identify and notify patients when diagnostic errors occur. The least implemented practices included convening a multidisciplinary team focused on diagnostic safety and quality, a CEO commitment to diagnostic excellence, conducting diagnosis-focused risk assessments, and training clinicians to optimize clinical reasoning in the diagnostic process. CONCLUSIONS: The findings suggest large and important implementation gaps for practices related to diagnostic excellence and can inform new initiatives to promote diagnostic excellence in US hospitals.

12.
JCI Insight ; 9(17)2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39088276

RÉSUMÉ

Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder leading to a block in long-chain fatty acid ß-oxidation. Mutations in HADHA and HADHB, which encode the TFP α and ß subunits, respectively, usually result in combined TFP deficiency. A single common mutation, HADHA c.1528G>C (p.E510Q), leads to isolated 3-hydroxyacyl-CoA dehydrogenase deficiency. TFP also catalyzes a step in the remodeling of cardiolipin (CL), a phospholipid critical to mitochondrial membrane stability and function. We explored the effect of mutations in TFP subunits on CL and other phospholipid content and composition and the consequences of these changes on mitochondrial bioenergetics in patient-derived fibroblasts. Abnormalities in these parameters varied extensively among different fibroblasts, and some cells were able to maintain basal oxygen consumption rates similar to controls. Although CL reduction was universally identified, a simultaneous increase in monolysocardiolipins was discrepant among cells. A similar profile was seen in liver mitochondria isolates from a TFP-deficient mouse model. Response to new potential drugs targeting CL metabolism might be dependent on patient genotype.


Sujet(s)
Cardiolipides , Métabolisme énergétique , Fibroblastes , Erreurs innées du métabolisme lipidique , Sous-unité alpha de la protéine trifonctionnelle mitochondriale , Cardiolipides/métabolisme , Animaux , Humains , Souris , Sous-unité alpha de la protéine trifonctionnelle mitochondriale/métabolisme , Sous-unité alpha de la protéine trifonctionnelle mitochondriale/génétique , Métabolisme énergétique/génétique , Fibroblastes/métabolisme , Erreurs innées du métabolisme lipidique/métabolisme , Erreurs innées du métabolisme lipidique/génétique , Erreurs innées du métabolisme lipidique/anatomopathologie , Sous-unité bêta de la protéine trifonctionnelle mitochondriale/métabolisme , Sous-unité bêta de la protéine trifonctionnelle mitochondriale/génétique , Mitochondries/métabolisme , Mutation , Protéine trifonctionnelle mitochondriale/déficit , Protéine trifonctionnelle mitochondriale/métabolisme , Protéine trifonctionnelle mitochondriale/génétique , Rhabdomyolyse/métabolisme , Rhabdomyolyse/génétique , Rhabdomyolyse/anatomopathologie , Myopathies mitochondriales/métabolisme , Myopathies mitochondriales/génétique , Myopathies mitochondriales/anatomopathologie , Consommation d'oxygène , Mâle , Modèles animaux de maladie humaine , Lysophospholipides , Cardiomyopathies , Maladies du système nerveux
13.
Environ Sci Technol ; 58(29): 13087-13098, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-38995999

RÉSUMÉ

Per- and polyfluoroalkyl substances (PFAS) enter the marine food web, accumulate in organisms, and potentially have adverse effects on predators and consumers of seafood. However, evaluations of PFAS in meso-to-apex predators, like sharks, are scarce. This study investigated PFAS occurrence in five shark species from two marine ecosystems with contrasting relative human population densities, the New York Bight (NYB) and the coastal waters of The Bahamas archipelago. The total detected PFAS (∑PFAS) concentrations in muscle tissue ranged from 1.10 to 58.5 ng g-1 wet weight, and perfluorocarboxylic acids (PFCAs) were dominant. Fewer PFAS were detected in Caribbean reef sharks (Carcharhinus perezi) from The Bahamas, and concentrations of those detected were, on average, ∼79% lower than in the NYB sharks. In the NYB, ∑PFAS concentrations followed: common thresher (Alopias vulpinus) > shortfin mako (Isurus oxyrinchus) > sandbar (Carcharhinus plumbeus) > smooth dogfish (Mustelus canis). PFAS precursors/intermediates, such as 2H,2H,3H,3H-perfluorodecanoic acid and perfluorooctanesulfonamide, were only detected in the NYB sharks, suggesting higher ambient concentrations and diversity of PFAS sources in this region. Ultralong-chain PFAS (C ≥ 10) were positively correlated with nitrogen isotope values (δ15N) and total mercury in some species. Our results provide some of the first baseline information on PFAS concentrations in shark species from the northwest Atlantic Ocean, and correlations between PFAS, stable isotopes, and mercury further contextualize the drivers of PFAS occurrence.


Sujet(s)
Requins , Polluants chimiques de l'eau , Animaux , Requins/métabolisme , Surveillance de l'environnement , Bahamas , Fluorocarbones/analyse , État de New York , Chaine alimentaire
15.
Sci Rep ; 14(1): 16799, 2024 07 22.
Article de Anglais | MEDLINE | ID: mdl-39039107

RÉSUMÉ

The auditory steady state response (ASSR) arises when periodic sounds evoke stable responses in auditory networks that reflect the acoustic characteristics of the stimuli, such as the amplitude of the sound envelope. Larger for some stimulus rates than others, the ASSR in the human electroencephalogram (EEG) is notably maximal for sounds modulated in amplitude at 40 Hz. To investigate the local circuit underpinnings of the large ASSR to 40 Hz amplitude-modulated (AM) sounds, we acquired skull EEG and local field potential (LFP) recordings from primary auditory cortex (A1) in the rat during the presentation of 20, 30, 40, 50, and 80 Hz AM tones. 40 Hz AM tones elicited the largest ASSR from the EEG acquired above auditory cortex and the LFP acquired from each cortical layer in A1. The large ASSR in the EEG to 40 Hz AM tones was not due to larger instantaneous amplitude of the signals or to greater phase alignment of the LFP across the cortical layers. Instead, it resulted from decreased latency variability (or enhanced temporal consistency) of the 40 Hz response. Statistical models indicate the EEG signal was best predicted by LFPs in either the most superficial or deep cortical layers, suggesting deep layer coordinators of the ASSR. Overall, our results indicate that the recruitment of non-uniform but more temporally consistent responses across A1 layers underlie the larger ASSR to amplitude-modulated tones at 40 Hz.


Sujet(s)
Stimulation acoustique , Cortex auditif , Électroencéphalographie , Potentiels évoqués auditifs , Cortex auditif/physiologie , Électroencéphalographie/méthodes , Potentiels évoqués auditifs/physiologie , Rats , Animaux , Mâle , Perception auditive/physiologie , Humains
16.
Am J Vet Res ; : 1-7, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39013399

RÉSUMÉ

OBJECTIVE: To develop an accessible ruminant immune challenge model for rapid in vivo assessments of feed additives. ANIMALS: 60 hair-breed ram lambs. METHODS: Sheep were randomly assigned to 1 of 4 treatments: treatment 1, not immunosuppressed, control fed (n = 12); treatment 2, immunosuppressed, supplemented with a yeast and botanical extract (n = 18); treatment 3, immunosuppressed, supplemented with a blend of natural aluminosilicates and yeast components (n = 18); and treatment 4, immunosuppressed, control fed (n = 12). Twice-daily injections of dexamethasone (Dex; 0.1 mg/kg bodyweight, SC) were used to induce immunosuppression throughout the study (from September 25, 2020, to November 2, 2020). All sheep were immunized with keyhole limpet hemocyanin (KLH) on days 0 and 14 and injected with heat-aggregated KLH, ID, to induce a skin induration on day 15. Measurements included body weight (BW), average daily gain (ADG), CBC, and skin induration diameter. RESULTS: Dex treatment resulted in reduced BW and ADG that was not mitigated by either feed additive. Dex reduced lymphocyte percentage, RBC count, hemoglobin, hematocrit, and skin induration diameter and increased concentrations of granulocytes and granulocyte percentage. Effects on hematocrit, hemoglobin, RBC, and skin induration diameter were mitigated with the addition of feed additives. CLINICAL RELEVANCE: The described model is a tool to evaluate the ability of feed additives to mitigate the immunosuppressive effects of Dex.

17.
J Hum Hypertens ; 38(9): 655-662, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39020025

RÉSUMÉ

Previous research shows that exercise pressor and metaboreflex responses are significantly exaggerated in individuals with metabolic syndrome, but it is unclear if these exaggerated responses extend to the cold pressor test (CPT). This study tested the hypothesis that, contrary to previously reported exaggerated responses during exercise, CPT responses would not be significantly exaggerated in individuals with MetS compared to matched controls. Eleven individuals with MetS and eleven control participants matched by age, race, sex, and ethnicity completed a cardiometabolic prescreening and a CPT. Each CPT required participants to immerse their hand in ice water for two minutes while beat-by-beat blood pressure, heart rate (HR), and leg blood flow (LBF) were continuously measured. Leg vascular conductance (LVC) was calculated as LBF divided by mean arterial pressure (MAP). The precent changes in MAP, systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, LBF, and LVC were compared across time (BL vs. Minutes 1 and 2 of CPT) and between groups (MetS vs. Control) using repeated measures analyses of variance. As expected, MAP (f = 32.11, p < 0.001), SBP (f = 23.18, p < 0.001), DBP (f = 40.39, p < 0.001), and HR (f = 31.81, p < 0.001) increased during the CPT, and LBF (f = 4.75, p = 0.014) and LVC (f = 13.88, p < 0.001) decreased. However, no significant main effects of group or group by time interactions were observed (f ≤ 0.391, p ≥ 0.539). These findings indicate that the hemodynamic responses to the CPT are not significantly exaggerated in MetS, and therefore, previous reports of exaggerated exercise pressor and metaboreflex responses in MetS cannot be attributed to generalized sympathetic overexcitability.


Sujet(s)
Basse température , Hémodynamique , Syndrome métabolique X , Humains , Syndrome métabolique X/physiopathologie , Syndrome métabolique X/diagnostic , Syndrome métabolique X/ethnologie , Mâle , Femelle , Études cas-témoins , Adulte , Adulte d'âge moyen , Hémodynamique/physiologie , Rythme cardiaque , Pression sanguine/physiologie , Débit sanguin régional
18.
J Immunother Cancer ; 12(7)2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39053946

RÉSUMÉ

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were ≥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.


Sujet(s)
Carcinome à cellules de Merkel , Ipilimumab , Thérapie de rattrapage , Humains , Ipilimumab/usage thérapeutique , Carcinome à cellules de Merkel/traitement médicamenteux , Thérapie de rattrapage/méthodes , Mâle , Femelle , Tumeurs cutanées/traitement médicamenteux , Sujet âgé , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Inhibiteurs de points de contrôle immunitaires/effets indésirables , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Sujet âgé de 80 ans ou plus , Études rétrospectives
19.
Am J Hum Biol ; : e24141, 2024 Jul 22.
Article de Anglais | MEDLINE | ID: mdl-39034709

RÉSUMÉ

OBJECTIVES: Visceral adipose tissue (VAT) is highly associated with metabolic syndrome (MetS), which is rapidly increasing in young adults. However, accessible VAT measurement methods are limited, restricting the use of VAT in early detection. This cross-sectional study sought to determine if near-infrared reactance spectroscopy (NIRS)-derived VAT (VATNIRS) was associated with MetS in a multi-ethnic sample of young adults. METHODS: A total of 107 male and female (F:62, M:45) participants (age: 23.0 ± 4.3y; BMI: 27.1 ± 6.6 kg/m2) completed measurements of fasting blood pressure, blood glucose (FBG), blood lipids, and anthropometric assessments including waist circumference and VATNIRS. MetS severity (MetSindex) was calculated from the aforementioned risk factors using sex and race-specific equations. RESULTS: VATNIRS was higher in participants with, and at risk for, MetS compared to those with lower risks (all p < .001). VATNIRS was positively associated with MetSindex for all groups (all p < .001). VATNIRS showed positive associations with systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), LDL-C and LDL-C-related biomarkers, and FBG; and negative associations with HDL-C and HDL-C-to-total cholesterol ratio (all p < .050). Associations between VATNIRS and blood pressure for females, and LDL-C and LDL-C-related biomarkers for males, were nonsignificant (all p > .050). VATNIRS was positively associated with DBP in African-American participants, and SBP in White participants, resulting in positive associations with MAP for both groups (all p < .050). CONCLUSIONS: VATNIRS is associated with MetS and individual MetS risks factors in a multi-ethnic sample of young adults; providing a noninvasive, cost-effective, portable, and accessible method that may assist in the early detection of MetS and other cardiometabolic abnormalities.

20.
Commun Biol ; 7(1): 822, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38971889

RÉSUMÉ

Translational studies benefit from experimental designs where laboratory organisms use human-relevant behaviors. One such behavior is decision-making, however studying complex decision-making in rodents is labor-intensive and typically restricted to two levels of cost/reward. We design a fully automated, inexpensive, high-throughput framework to study decision-making across multiple levels of rewards and costs: the REward-COst in Rodent Decision-making (RECORD) system. RECORD integrates three components: 1) 3D-printed arenas, 2) custom electronic hardware, and 3) software. We validated four behavioral protocols without employing any food or water restriction, highlighting the versatility of our system. RECORD data exposes heterogeneity in decision-making both within and across individuals that is quantifiably constrained. Using oxycodone self-administration and alcohol-consumption as test cases, we reveal how analytic approaches that incorporate behavioral heterogeneity are sensitive to detecting perturbations in decision-making. RECORD is a powerful approach to studying decision-making in rodents, with features that facilitate translational studies of decision-making in psychiatric disorders.


Sujet(s)
Comportement animal , Prise de décision , Animaux , Mâle , Rats , Souris , Oxycodone/administration et posologie , Récompense , Consommation d'alcool/psychologie , Comportement alimentaire , Autoadministration , Logiciel
SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE