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1.
JID Innov ; 4(3): 100272, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736521

RESUMEN

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and thiazides (RR = 1.10, 95% CI = 1.04-1.16); for squamous cell carcinoma with calcium channel blockers (RR = 1.08, 95% CI = 1.01-1.14), diuretics (RR = 1.29, 95% CI = 1.17-1.43), and thiazides (RR = 1.36, 95% CI = 1.15-1.61); and for melanoma in angiotensin-converting enzyme inhibitors (RR = 1.09, 95% CI = 1.03-1.14), calcium channel blockers (RR = 1.08, 95% CI = 1.03-1.12), and thiazides (RR = 1.09, 95% CI = 1.02-1.17). The quality of evidence was low or very low. We observed evidence for dose-response for thiazides with basal cell carcinoma; angiotensin-converting enzyme inhibitors, diuretics, and thiazides with squamous cell carcinoma; and angiotensin-converting enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.

2.
JAMA Dermatol ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776099

RESUMEN

Importance: Rates of physician-diagnosed eczema have been increasing among older adults, but little is known regarding the pathophysiologic processes and best treatments in this subgroup. Preliminary data suggest that medications-antihypertensive medications in particular-may contribute to eczematous dermatitis; however, there are limited population-based data on the proportion of eczematous dermatitis diagnoses among older adults that may be attributed to antihypertensive drugs. Objectives: To determine whether antihypertensive drug use is associated with eczematous dermatitis in older adults. Design, Settings, and Participants: This was a longitudinal cohort study of a population-based sample of individuals 60 years and older without a diagnosis of eczematous dermatitis at baseline. It was conducted at primary care practices participating in The Health Improvement Network in the United Kingdom from January 1, 1994, to January 1, 2015. Data analyses were performed from January 6, 2020, to February 6, 2024. Exposure: Exposure date by first prescription for an antihypertensive drug within each drug class. Main outcome measures: Newly active eczematous dermatitis was based on the first date for 1 of the 5 most common eczema codes used in a previously validated algorithm. Results: Among the total study sample of 1 561 358 older adults (mean [SD] age, 67 [9] years; 54% female), the overall prevalence of eczematous dermatitis was 6.7% during a median (IQR) follow-up duration of 6 (3-11) years. Eczematous dermatitis incidence was higher among participants receiving antihypertensive drugs than those who did not (12 vs 9 of 1000 person-years of follow-up). Adjusted Cox proportional hazard models found that participants who received any antihypertensive drugs had a 29% increased hazard rate of any eczematous dermatitis (hazard ratio [HR], 1.29; 95% CI, 1.26-1.31). When assessing each antihypertensive drug class individually, the largest effect size was observed for diuretic drugs (HR, 1.21; 95% CI, 1.19-1.24) and calcium channel blockers (HR, 1.16; 95% CI, 1.14-1.18), and the smallest effect sizes were for angiotensin-converting enzyme inhibitors (HR, 1.02; 95% CI, 1.00-1.04) and ß-blockers (HR, 1.04; 95% CI, 1.02-1.06). Conclusions and Relevance: This cohort study found that antihypertensive drugs were associated with a small increased rate of eczematous dermatitis, with effect sizes largest for calcium channel blockers and diuretic drugs, and smallest for angiotensin-converting enzyme inhibitors and ß-blockers. Although additional research is needed to understand the mechanisms underlying the association, these data could be helpful to clinicians to guide management when a patient presents with eczematous dermatitis in older age.

3.
bioRxiv ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38712183

RESUMEN

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that traveled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced traveling wave. A depression of calcium signals followed the wave, during which we observed atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioral measures. Neural and behavioral changes mostly recovered over hours to days in our mild-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results provide novel spatial and temporal views of neural adaptations that occur at cortical sites remote to a focal brain injury.

4.
J Infect Dis ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716969

RESUMEN

BACKGROUND: Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for SARS-CoV-2 infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. METHODS: Participants were non-hospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. RESULTS: Study participants receiving single- and dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared to single-active mAb, treatment with dual-active mAbs led to faster viral load decline at study day 3 (p < 0.001) and day 7 (p < 0.01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, P < 0.001), and more frequently detected in the setting of single-active compared to dual-active mAb treatment (7.2% vs 1.1%, p < 0.01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. CONCLUSION: Compared to single-active mAb therapy, dual-active mAbs led to similar clinical outcomes, but significantly faster viral load decline and a lower risk of emergent resistance.

5.
Open Forum Infect Dis ; 11(5): ofae212, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38756763

RESUMEN

Background: Persistence of HIV-1 in reservoirs necessitates life-long antiretroviral therapy (ART). There are conflicting data using genetic analysis on whether persistence includes an actively replicating reservoir with strong evidence arguing against replication. Methods: We investigated the possibility of ongoing viral evolution during suppressive therapy by comparing near full-length viral genomic sequences using phylogenetic analysis of viral RNA in plasma before therapy initiation early after infection and from virus induced to grow from the latent reservoir after a period of suppressive ART. We also focused our analysis on evidence of selective pressure by drugs in the treatment regimen and at sites of selective pressure by the adaptive immune response. Results: Viral genomes induced to grow from the latent reservoir from 10 participants with up to 9 years on suppressive ART were highly similar to the nearly homogeneous sequences in plasma taken early after infection at ART initiation. This finding was consistent across the entire genome and when the analysis focused on sites targeted by the drug regimen and by host selective pressure of antibody and cytotoxic T cells. The lack of viral evolution away from pretherapy sequences in spite of demonstrated selective pressure is most consistent with a lack of viral replication during reservoir persistence. Conclusions: These results do not support ongoing viral replication as a mechanism of HIV-1 persistence during suppressive ART.

6.
J Neural Eng ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621379

RESUMEN

Objective. This paper presents data-driven solutions to address two challenges in the problem of linking neural data and behavior: 1) unsupervised analysis of behavioral data and automatic label generation from behavioral observations, and 2) extraction of subject-invariant features for the development of generalized neural decoding models. Approach. For behavioral analysis and label generation, an unsupervised method, which employs an autoencoder to transform behavior data into a cluster-friendly feature space is presented. The model iteratively refines the assigned clusters with soft clustering assignment loss, and gradually improves the learned feature representations. To address subject variability in decoding neural activity, adversarial learning in combination with a long short-term memory-based adversarial variational autoencoder (LSTM-AVAE) model is employed. By using an adversary network to constrain the latent representations, the model captures shared information among subjects' neural activity, making it proper for cross-subject transfer learning. Main results. The proposed approach is evaluated using cortical recordings of Thy1-GCaMP6s transgenic mice obtained via widefield calcium imaging during a motivational licking behavioral experiment. The results show that the proposed model achieves an accuracy of 89.7% in cross-subject neural decoding, outperforming other well-known autoencoder-based feature learning models. These findings suggest that incorporating an adversary network eliminates subject dependency in representations, leading to improved cross-subject transfer learning performance, while also demonstrating the effectiveness of LSTM-based models in capturing the temporal dependencies within neural data. Significance. Results demonstrate the feasibility of the proposed framework in unsupervised clustering and label generation of behavioral data, as well as achieving high accuracy in cross-subject neural decoding, indicating its potentials for relating neural activity to behavior.

7.
bioRxiv ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38585753

RESUMEN

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry and is likely involved in behavioral modulation and sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of sensorimotor processing, yet the role of POm-striatal projections has remained undetermined. Using optogenetics with slice electrophysiology, we found that POm provides robust synaptic input to direct and indirect pathway striatal spiny projection neurons (D1- and D2-SPNs, respectively) and parvalbumin-expressing fast spiking interneurons (PVs). During the performance of a whisker-based tactile discrimination task, POm-striatal projections displayed learning-related activation correlating with anticipatory, but not reward-related, pupil dilation. Inhibition of POm-striatal axons across learning caused slower reaction times and an increase in the number of training sessions for expert performance. Our data indicate that POm-striatal inputs provide a behaviorally relevant arousal-related signal, which may prime striatal circuitry for efficient integration of subsequent choice-related inputs.

8.
J Virol ; 98(3): e0179823, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38376258

RESUMEN

Although antiretroviral therapy (ART) is effective at suppressing HIV replication, a viral reservoir persists that can reseed infection if ART is interrupted. Curing HIV will require elimination or containment of this reservoir, but the size of the HIV reservoir is highly variable between individuals. To evaluate the size of the HIV reservoir, several assays have been developed, including PCR-based assays for viral DNA, the intact proviral DNA assay, and the quantitative viral outgrowth assay (QVOA). QVOA is the gold standard assay for measuring inducible replication-competent proviruses, but this assay is technically challenging and time-consuming. To begin progress toward a more rapid and less laborious tool for quantifying cells infected with replication-competent HIV, we developed the Microwell Outgrowth Assay, in which infected CD4 T cells are co-cultured with an HIV-detecting reporter cell line in a polydimethylsiloxane (PDMS)/polystyrene array of nanoliter-sized wells. Transmission of HIV from infected cells to the reporter cell line induces fluorescent reporter protein expression that is detected by automated scanning across the array. Using this approach, we were able to detect HIV-infected cells from ART-naïve people with HIV (PWH) and from PWH on ART with large reservoirs. Furthermore, we demonstrate that infected cells can be recovered from individual rafts and used to analyze the diversity of viral sequences. Although additional development and optimization will be required for quantifying the reservoir in PWH with small latent reservoirs, this assay may be a useful prototype for microwell assays of infected cells.IMPORTANCEMeasuring the size of the HIV reservoir in people with HIV (PWH) will be important for determining the impact of HIV cure strategies. However, measuring this reservoir is challenging. We report a new method for quantifying HIV-infected cells that involves culturing cells from PWH in an array of microwells with a cell line that detects HIV infection. We show that this approach can detect rare HIV-infected cells and derive detailed virus sequence information for each infected cell.


Asunto(s)
Infecciones por VIH , Virología , Humanos , Linfocitos T CD4-Positivos , Línea Celular , ADN Viral , Infecciones por VIH/virología , Provirus/genética , Carga Viral , Latencia del Virus , Virología/métodos
9.
J Infect Dis ; 229(3): 743-752, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38349333

RESUMEN

BACKGROUND: The histone deacetylase inhibitor vorinostat (VOR) can reverse human immunodeficiency virus type 1 (HIV-1) latency in vivo and allow T cells to clear infected cells in vitro. HIV-specific T cells (HXTCs) can be expanded ex vivo and have been safely administered to people with HIV (PWH) on antiretroviral therapy. METHODS: Six PWH received infusions of 2 × 107 HXTCs/m² with VOR 400 mg, and 3 PWH received infusions of 10 × 107 HXTCs/m² with VOR. The frequency of persistent HIV by multiple assays including quantitative viral outgrowth assay (QVOA) of resting CD4+ T cells was measured before and after study therapy. RESULTS: VOR and HXTCs were safe, and biomarkers of serial VOR effect were detected, but enhanced antiviral activity in circulating cells was not evident. After 2 × 107 HXTCs/m² with VOR, 1 of 6 PWH exhibited a decrease in QVOA, and all 3 PWH exhibited such declines after 10 × 107 HXTCs/m² and VOR. However, most declines did not exceed the 6-fold threshold needed to definitively attribute decline to the study intervention. CONCLUSIONS: These modest effects provide support for the strategy of HIV latency reversal and reservoir clearance, but more effective interventions are needed to yield the profound depletion of persistent HIV likely to yield clinical benefit. Clinical Trials Registration. NCT03212989.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Vorinostat/uso terapéutico , Vorinostat/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Linfocitos T CD4-Positivos , Tratamiento Basado en Trasplante de Células y Tejidos , Latencia del Virus
10.
PLoS Pathog ; 20(2): e1011974, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38422171

RESUMEN

People with HIV-1 (PWH) on antiretroviral therapy (ART) can maintain undetectable virus levels, but a small pool of infected cells persists. This pool is largely comprised of defective proviruses that may produce HIV-1 proteins but are incapable of making infectious virus, with only a fraction (~10%) of these cells harboring intact viral genomes, some of which produce infectious virus following ex vivo stimulation (i.e. inducible intact proviruses). A majority of the inducible proviruses that persist on ART are formed near the time of therapy initiation. Here we compared proviral DNA (assessed here as 3' half genomes amplified from total cellular DNA) and inducible replication competent viruses in the pool of infected cells that persists during ART to determine if the original infection of these cells occurred at comparable times prior to therapy initiation. Overall, the average percent of proviruses that formed late (i.e. around the time of ART initiation, 60%) did not differ from the average percent of replication competent inducible viruses that formed late (69%), and this was also true for proviral DNA that was hypermutated (57%). Further, there was no evidence that entry into the long-lived infected cell pool was impeded by the ability to use the CXCR4 coreceptor, nor was the formation of long-lived infected cells enhanced during primary infection, when viral loads are exceptionally high. We observed that infection of cells that transitioned to be long-lived was enhanced among people with a lower nadir CD4+ T cell count. Together these data suggest that the timing of infection of cells that become long-lived is impacted more by biological processes associated with immunodeficiency before ART than the replication competency and/or cellular tropism of the infecting virus or the intactness of the provirus. Further research is needed to determine the mechanistic link between immunodeficiency and the timing of infected cells transitioning to the long-lived pool, particularly whether this is due to differences in infected cell clearance, turnover rates and/or homeostatic proliferation before and after ART.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Provirus/genética , VIH-1/genética , Antirretrovirales/farmacología , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Linfocitos T CD4-Positivos , ADN Viral/genética , ADN Viral/metabolismo , Carga Viral , Tropismo
12.
JAMA Dermatol ; 160(4): 441-446, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38381409

RESUMEN

Importance: The use of patient-reported outcome measures (PROMs) potentially holds promise as an opportunity to improve outcomes and quality of care for patients with skin disease, but the routine use of PROMs remains limited. While the Patient-Reported Outcomes Measurement Information System (PROMIS) has several strengths and domains relevant to those with chronic skin disease, it is not clear which are most useful. Objective: To determine which PROMIS domains are most meaningful to those with chronic skin disease to develop a PROMIS profile that effectively captures the experience of living with these skin diseases. Design, Setting, and Participants: This cross-sectional study was based on data gathered from an internet survey that was administered to a sample of adult respondents in the US on the Prolific Platform and ResearchMatch and through the National Psoriasis Foundation. A list of PROMIS domains relevant to chronic skin disease was developed through literature review. These domains were included in a best-worst scaling exercise, in which participants were shown 12 sets of 4 domains and asked to choose which domain in each set was the most important and least important to their experience. Participants completed the survey between December 2022 and June 2023. Data were analyzed in June 2023. Main Outcomes and Measures: Ratio-scaled preference score for each of the domains. Results: Of 939 total participants, 559 (59.5%) were female, 20 (2.1%) gender nonconforming, 7 (0.7%) transgender men, and 1 (0.1%) transgender women; there were 4 American Indian/Alaska Native (0.4%), 50 Asian (5.3%), 63 Black (6.7%), 66 Hispanic or Latino/a/x (7.0%), 2 Native Hawaiian/Pacific Islander (0.2%), 749 White (79.8%), and 42 multiracial individuals (4.5%). The survey was completed by 200 participants with acne, 316 with psoriasis, 199 with atopic dermatitis, and 224 with various chronic skin diseases. For those with acne, the highest-scored domains were body image (15.66), appearance (14.96), life satisfaction (11.29), depression (9.25), and anxiety (9.18). For those with psoriasis, the highest-scored domains were life satisfaction (11.31), appearance (11.05), itch (10.98), pain (9.97), and body image (8.75). For those with atopic dermatitis, the highest-scored domains were itch (12.60), life satisfaction (11.65), appearance (11.40), body image (11.25), and pain (10.03). Conclusion and Relevance: The results of this study suggest that body image, appearance, life satisfaction, itch, pain, anxiety, and depression were highly rated across the surveys. By identifying the PROMIS domains most important to individuals with chronic skin disease, clinicians can choose the domains that are most relevant to patients. In addition, this may guide the construction of a PROMIS profile that effectively captures the experience of living with these skin diseases and can serve as a patient-reported measure of disease severity and treatment effectiveness.


Asunto(s)
Acné Vulgar , Dermatitis Atópica , Psoriasis , Adulto , Masculino , Humanos , Femenino , Estudios Transversales , Medición de Resultados Informados por el Paciente , Dolor , Enfermedad Crónica
13.
J Am Acad Dermatol ; 90(5): 945-952, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38340127

RESUMEN

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. OBJECTIVE: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). METHODS: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. RESULTS: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. LIMITATIONS: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. CONCLUSION: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.


Asunto(s)
Dermatitis Atópica , Eccema , Dermatosis de la Pierna , Humanos , Compuestos de Boro/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Dermatitis Atópica/diagnóstico , Método Doble Ciego , Eccema/tratamiento farmacológico , Pomadas/uso terapéutico , Piel , Resultado del Tratamiento , Prueba de Estudio Conceptual
15.
JMIR Form Res ; 8: e52200, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38277207

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is a chronic skin condition that millions of people around the world live with each day. Performing research into identifying the causes and treatment for this disease has great potential to provide benefits for these individuals. However, AD clinical trial recruitment is not a trivial task due to the variance in diagnostic precision and phenotypic definitions leveraged by different clinicians, as well as the time spent finding, recruiting, and enrolling patients by clinicians to become study participants. Thus, there is a need for automatic and effective patient phenotyping for cohort recruitment. OBJECTIVE: This study aims to present an approach for identifying patients whose electronic health records suggest that they may have AD. METHODS: We created a vectorized representation of each patient and trained various supervised machine learning methods to classify when a patient has AD. Each patient is represented by a vector of either probabilities or binary values, where each value indicates whether they meet a different criteria for AD diagnosis. RESULTS: The most accurate AD classifier performed with a class-balanced accuracy of 0.8036, a precision of 0.8400, and a recall of 0.7500 when using XGBoost (Extreme Gradient Boosting). CONCLUSIONS: Creating an automated approach for identifying patient cohorts has the potential to accelerate, standardize, and automate the process of patient recruitment for AD studies; therefore, reducing clinician burden and informing the discovery of better treatment options for AD.

16.
eNeuro ; 11(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38164611

RESUMEN

The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS and, as a result, exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution of striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex vivo patch clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs; however, there is a consistent bias towards the M1 input in SPNs that is not found in FSIs. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPN and FSI dendrites. Notably, closely localized M1 and S1 clusters of inputs were more prevalent in SPNs than FSIs, suggesting that cortical inputs are integrated through cell-type specific mechanisms. Our results suggest that the stronger functional connectivity from M1 to SPNs compared to S1, as previously observed, is due to a higher quantity of synaptic inputs. Our results have implications for how sensorimotor integration is performed in the striatum through cell-specific differences in corticostriatal connections.


Asunto(s)
Neuronas , Vibrisas , Ratones , Masculino , Femenino , Animales , Neuronas/fisiología , Interneuronas/fisiología , Cuerpo Estriado/metabolismo , Neostriado
17.
Artículo en Inglés | MEDLINE | ID: mdl-38258807

RESUMEN

Objective: The goal of this investigation was to use comprehensive prediction modeling tools and available genetic information to try to improve upon the performance of simple clinical models in predicting whether a diabetic foot ulcer (DFU) will heal. Approach: We utilized a cohort study (n = 206) that included clinical factors, measurements of circulating endothelial precursor cells (CEPCs), and fine sequencing of the NOS1AP gene. We derived and selected relevant predictive features from this patient-level information using statistical and machine learning techniques. We then developed prognostic models using machine learning approaches and assessed predictive performance. The presentation is consistent with TRIPOD requirements. Results: Models using baseline clinical and CEPC data had an area under the receiver operating characteristic curve (AUC) of 0.73 (0.66-0.80). Models using only single nucleotide polymorphisms (SNPs) of the NOS1AP gene had an AUC of 0.67 (95% confidence interval, CI: [0.59-0.75]). However, models incorporating baseline and SNP information resulted in improved AUC (0.80, 95% CI [0.73-0.87]). Innovation: We provide a rigorous analysis demonstrating the predictive potential of genetic information in DFU healing. In this process, we present a framework for using advanced statistical and bioinformatics techniques for creating superior prognostic models and identify potentially predictive SNPs for future research. Conclusion: We have developed a new benchmark for which future predictive models can be compared against. Such models will enable wound care experts to more accurately predict whether a patient will heal and aid clinical trialists in designing studies to evaluate therapies for subjects likely or unlikely to heal.

20.
JAMA Dermatol ; 160(1): 109-111, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019561

RESUMEN

This cohort study examines raw and age-adjusted differences in the incidence of keratinocyte carcinoma among Medicare beneficiaries by race and ethnicity.


Asunto(s)
Carcinoma , Etnicidad , Humanos , Anciano , Estados Unidos/epidemiología , Incidencia , Medicare , Queratinocitos
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