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1.
J Am Soc Cytopathol ; 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38589274

RESUMEN

INTRODUCTION: Biliary brushing (BB) cytology has a sensitivity of 15%-65% and specificity approaching 100% for detecting malignancy. Fluorescence in-situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of malignancies with reported sensitivity of 43%-84%. We sought to evaluate the performance of FISH in BB with equivocal cytology at our institution. MATERIALS AND METHODS: Patients with atypical and suspicious BB with concurrent diagnostic FISH performed at our institution from 2014 to 2021 were identified through a query of our pathology database. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed for pathology results and outcomes. Patients were classified malignant if they had positive pathology or documented clinical impression of malignancy and benign if they had negative pathology and/or documented benign clinical course for at least 12 months. RESULTS: We identified 254 equivocal BB (238 atypical/16 suspicious) with concurrent FISH results from 191 patients (105 benign, 86 malignant). 12% (22/191) of patients were FISH positive. Twenty-four percent (21/86) of patients with malignancy had positive FISH but were nonspecific for pancreaticobiliary/ampullary adenocarcinomas. Almost all positive FISH were associated with malignancy (21/22; 95%). There was 1 positive FISH in a patient with primary sclerosing cholangitis who had a benign outcome. CONCLUSIONS: The small number of positive FISH results in BB with equivocal cytology raises the question of the optimal criteria for malignancy. Using only polysomy could result in lower sensitivity.

2.
Front Aging Neurosci ; 16: 1320808, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38425784

RESUMEN

Introduction: Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1. Methods: We used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor (Igf1r) deficiency and evaluated the development of cerebrovascular pathologies and cognitive dysfunction. Results: VSMC-specific Igf1r deficiency led to impaired cerebral myogenic autoregulation, independent of blood pressure changes, which was also associated with impaired spatial learning and memory function as measured by radial arm water maze and impaired motor learning measured by rotarod. In contrast, VSMC-specific IGF-1 receptor knockdown did not lead to cerebral microvascular rarefaction. Discussion: These studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.

3.
One Health Outlook ; 6(1): 3, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38504381

RESUMEN

BACKGROUND: The dynamic nature of zoonotic emergence, spillover and spread necessitates multisectoral coordination beyond national borders to encompass cross-boundary and regional cooperation. Designated points of entry (POEs), specifically ground crossings, serve as critical locales for establishing and maintaining robust prevention, detection, notification, coordination, and response mechanisms to transboundary emerging and re-emerging disease threats. In order to better assess One Health capacities for transboundary zoonotic diseases (TZD) prevention, detection and response we adapted an existing tool, One Health Systems Assessment for Priority Zoonoses (OHSAPZ), for a cross-border, POE setting in North Africa. METHODS: The One Health Transboundary Assessment for Priority Zoonoses (OHTAPZ) tool was used to support prioritization of transboundary zoonoses and analyze operational capacities between national and subnational-level human and animal health stakeholders from Libya and Tunisia. Country partners jointly identified and prioritized five TZDs of concern. Case study scenarios for each priority pathogen were used to elicit current disease operations, as well as multisectoral and bilateral engagement networks. Finally, a gap analysis was performed to determine bilateral strengths and weaknesses to TZDs. RESULTS: The five priority TZDs jointly confirmed to undergo One Health assessment were avian influenza (low and high pathogenic strains); brucellosis; Rift Valley fever; Crimean-Congo hemorrhagic fever; and rabies. Using the qualitative information collected, a transboundary systems map schematic was developed outlining the movement of human patients, animals, diagnostic samples, and routes of communication and coordination both within and between countries for zoonotic diseases. CONCLUSIONS: Analysis of current operations (prevention, detection, surveillance, laboratory capacity, quarantine/isolation, and response) and the resulting transboundary systems map schematic helped identify existing capacity strengths for certain priority pathogens, as well as challenges to timely information-sharing and coordination. We developed targeted recommendations to address these limitations for joint action planning between Libya and Tunisia.

4.
Proc Natl Acad Sci U S A ; 121(11): e2211711120, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38408214

RESUMEN

Today, relatively warm Circumpolar Deep Water is melting Thwaites Glacier at the base of its ice shelf and at the grounding zone, contributing to significant ice retreat. Accelerating ice loss has been observed since the 1970s; however, it is unclear when this phase of significant melting initiated. We analyzed the marine sedimentary record to reconstruct Thwaites Glacier's history from the early Holocene to present. Marine geophysical surveys were carried out along the floating ice-shelf margin to identify core locations from various geomorphic settings. We use sedimentological data and physical properties to define sedimentary facies at seven core sites. Glaciomarine sediment deposits reveal that the grounded ice in the Amundsen Sea Embayment had already retreated to within ~45 km of the modern grounding zone prior to ca. 9,400 y ago. Sediments deposited within the past 100+ y record abrupt changes in environmental conditions. On seafloor highs, these shifts document ice-shelf thinning initiating at least as early as the 1940s. Sediments recovered from deep basins reflect a transition from ice proximal to slightly more distal conditions, suggesting ongoing grounding-zone retreat since the 1950s. The timing of ice-shelf unpinning from the seafloor for Thwaites Glacier coincides with similar records from neighboring Pine Island Glacier. Our work provides robust new evidence that glacier retreat in the Amundsen Sea was initiated in the mid-twentieth century, likely associated with climate variability.

5.
Geroscience ; 46(3): 3481-3501, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38388918

RESUMEN

Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Circulating IGF-1 deficiency leads to the development of CMH and other signs of cerebrovascular dysfunction. Here our goal was to understand the contribution of IGF-1 signaling on vascular smooth muscle cells (VSMCs) to the development of CMH and associated gait defects. We used an inducible VSMC-specific promoter and an IGF-1 receptor (Igf1r) floxed mouse line (Myh11-CreERT2 Igf1rf/f) to knockdown Igf1r. Angiotensin II in combination with L-NAME-induced hypertension was used to elicit CMH. We observed that VSMC-specific Igf1r knockdown mice had accelerated development of CMH, and subsequent associated gait irregularities. These phenotypes were accompanied by upregulation of a cluster of pro-inflammatory genes associated with VSMC maladaptation. Collectively our findings support an essential role for VSMCs as a target for the vasoprotective effects of IGF-1, and suggest that VSMC dysfunction in aging may contribute to the development of CMH.


Asunto(s)
Hipertensión , Músculo Liso Vascular , Receptor IGF Tipo 1 , Anciano , Animales , Humanos , Ratones , Marcha , Hipertensión/genética , Hipertensión/complicaciones , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Receptor IGF Tipo 1/genética , Trastornos Neurológicos de la Marcha/genética
6.
J Neurosci ; 44(16)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38423763

RESUMEN

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons. Previous studies provided evidence that RBs fall into multiple subclasses; however, the number and molecular makeup of these potential RB subtypes have not been well defined. Using a single-cell RNA sequencing (scRNA-seq) approach, we demonstrate that larval RBs in zebrafish fall into three, largely nonoverlapping classes of neurons. We also show that RBs are molecularly distinct from trigeminal neurons in zebrafish. Cross-species transcriptional analysis indicates that one RB subclass is similar to a mammalian group of A-fiber sensory neurons. Another RB subclass is predicted to sense multiple modalities, including mechanical stimulation and chemical irritants. We leveraged our scRNA-seq data to determine that the fibroblast growth factor (Fgf) pathway is active in RBs. Pharmacological and genetic inhibition of this pathway led to defects in axon maintenance and RB cell death. Moreover, this can be phenocopied by treatment with dovitinib, an FDA-approved Fgf inhibitor with a common side effect of peripheral neuropathy. Importantly, dovitinib-mediated axon loss can be suppressed by loss of Sarm1, a positive regulator of neuronal cell death and axonal injury. This offers a molecular target for future clinical intervention to fight neurotoxic effects of this drug.


Asunto(s)
Células Receptoras Sensoriales , Pez Cebra , Animales , Pez Cebra/metabolismo , Animales Modificados Genéticamente , Supervivencia Celular , Células Receptoras Sensoriales/fisiología , Axones/fisiología , Análisis de la Célula Individual , Mamíferos
8.
Alzheimers Dement ; 20(2): 1013-1025, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37849026

RESUMEN

INTRODUCTION: Signatures of a type-I interferon (IFN-I) response are observed in the post mortem brain in Alzheimer's disease (AD) and other tauopathies. However, the effect of the IFN-I response on pathological tau accumulation remains unclear. METHODS: We examined the effects of IFN-I signaling in primary neural culture models of seeded tau aggregation and P301S-tau transgenic mouse models in the context of genetic deletion of the IFN-I receptor (IFNAR). RESULTS: Polyinosinic:polycytidylic acid (PolyI:C), a synthetic analog of viral nucleic acids, evoked a potent cytokine response that enhanced seeded aggregation of tau in an IFN-I-dependent manner. IFN-I-induced vulnerability could be pharmacologically prevented and was intrinsic to neurons. Aged P301S-tau mice lacking Ifnar1 had significantly reduced tau pathology compared to mice with intact IFN signaling. DISCUSSION: We identify a critical role for IFN-I in potentiating tau aggregation. IFN-I is therefore identified as a potential therapeutic target in AD and other tauopathies. HIGHLIGHTS: Type-I IFN (IFN-I) promotes seeded tau aggregation in neural cultures. IFNAR inhibition prevents IFN-I driven sensitivity to tau aggregation. IFN-I driven vulnerability is intrinsic to neurons. Tau pathology is significantly reduced in aged P301S-tau mice lacking IFNAR.


Asunto(s)
Enfermedad de Alzheimer , Interferón Tipo I , Tauopatías , Ratones , Animales , Proteínas tau/genética , Interferón Tipo I/uso terapéutico , Tauopatías/patología , Ratones Transgénicos , Enfermedad de Alzheimer/patología , Modelos Animales de Enfermedad
10.
Arch Pathol Lab Med ; 148(4): 409-418, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37622452

RESUMEN

CONTEXT.­: Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids. OBJECTIVE.­: To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions, as well as relevant clinicoradiologic contexts and ancillary tests. DATA SOURCES.­: Existing scientific and clinical literature as of January 2023. CONCLUSIONS.­: We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.


Asunto(s)
Adenocarcinoma , Mesotelioma Maligno , Mesotelioma , Derrame Pleural Maligno , Derrame Pleural , Humanos , Adenocarcinoma/diagnóstico , Biomarcadores de Tumor , Diagnóstico Diferencial , Inmunohistoquímica , Mesotelioma/diagnóstico , Mesotelioma/patología , Mesotelioma Maligno/diagnóstico , Derrame Pleural/diagnóstico , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patología
11.
Diabetes Res Clin Pract ; 207: 111060, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38110121

RESUMEN

AIMS: In the United States, evidence suggests that during the COVID-19 pandemic, admissions of patients with diabetes mellitus (DM) have increased. This study assessed hospital admission rates for pediatric type 1 (T1DM) and type 2 (T2DM) diabetes mellitus during 2019-2021, and the potential influence of the timing of various pandemic response measures. METHODS: Retrospective chart reviews were conducted of 854 T1DM and 135 T2DM hospital admissions between January 2019 and December 2021 in patients < 20 years old to collect demographic data, admission type, body mass index (BMI), and area deprivation index (ADI, a measure of socioeconomic vulnerability). Patients were divided into three cohorts based on their admission year: 2019 (Pre-pandemic), 2020 (Pandemic, Pre-vaccine), and 2021 (Pandemic, Post-vaccine). Admissions were categorized within each cohort by diagnosis (T1DM or T2DM) and clinical presentation (new onset, diabetic ketoacidosis: DKA). Cohorts were compared using an independent samples t-test for continuous variables or a chi-square test for categorical variables. RESULTS: The incidence of T2DM hospitalizations tripled during the pandemic, increasing from 18 in 2019 (Pre-pandemic), to 55 in 2020 (Pandemic, Pre-vaccine), and 62 in 2021 (Pandemic, Post-vaccine). The rate of patients presenting with DKA was 15.4 % (95 % CI: 4 %-26.9 %) higher in 2020 (Pandemic, Pre-vaccine) among patients with new-onset T1DM (72/139 vs. 52/143), and 22.5 % (95 % CI: 9.6 %-35.4 %) higher in 2020 (Pandemic, Pre-vaccine) among T2DM patients (9/40 vs. 0/14). This increased rate of new onset T2DM significantly correlated with younger age (P = 0.046) and higher ADI score (P = 0.017), but not with BMI. CONCLUSION: The incidence of T1DM hospitalizations did not increase during the pandemic; however, they tripled for T2DM patients. All new onset DM pediatric patients during the pandemic were more likely to present in DKA. Patients admitted with new onset T2DM were socioeconomically more vulnerable. For T1DM, the peak of local pediatric diabetes admissions in 2020 occurred slightly later coinciding with the reopening of primary care physicians (PCP) offices and schools.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Vacunas , Niño , Humanos , Adulto Joven , Adulto , Diabetes Mellitus Tipo 1/complicaciones , Pandemias , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/complicaciones , Hospitalización , Cetoacidosis Diabética/etiología , Diabetes Mellitus Tipo 2/complicaciones
12.
Am J Otolaryngol ; 45(1): 104074, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37865986

RESUMEN

IMPORTANCE: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population. OBJECTIVE: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified. Data analysis was performed in January 2022. MAIN OUTCOMES AND MEASURES: Dermatology Life Quality Index was modified (mDLQI) to assess patients' perceptions of their scars. The primary outcome was the mean mDLQI survey score with higher scores corresponding to worse perceptions. Three questions adapted from the Self-Consciousness Scale (SCS) were also included to assess awareness of appearance. All questions were scaled on a 0-3 Likert Scale. Tweedie generalized linear model was used to understand the relationship between mDLQI score and patient- and procedure-specific factors (including the three SCS survey questions). An additional exploratory logistic regression was performed to understand the risk factors for clinically significant mDLQI score change. RESULTS: A total of 67 patients (response rate 57 %) completed the survey with a mean mDLQI survey score of 0.84 (max 30). Although there was a statistically significant negative association between private insurance and mDLQI survey score (95 % Confidence Interval [CI]: -2.72 - -0.38), and a positive association between the SCS score and mDLQI survey score (95 % CI: 0.23-0.81) (p < 0.05), these variables were not found to be risk factors for a clinically significant difference in mDLQI on multivariable analysis. CONCLUSION: The majority of patients felt their neck scars did not interfere with their daily lives. Patient perceptions of neck scars were consistent despite differing patient characteristics and treatment regimens.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Disección del Cuello/efectos adversos , Calidad de Vida , Cicatriz/etiología , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Estudios de Casos y Controles , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/cirugía , Neoplasias Orofaríngeas/patología , Neoplasias de Cabeza y Cuello/cirugía , Percepción , Procedimientos Quirúrgicos Robotizados/efectos adversos
13.
JAMA Otolaryngol Head Neck Surg ; 150(2): 127-132, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38127340

RESUMEN

Importance: Despite the widespread use of fibula free flap (FFF) surgery for head and neck reconstruction, there are no studies assessing if early weight-bearing (EWB) affects postoperative recovery, and the timing of weight-bearing initiation following FFF surgery varies considerably across institutions. Therefore, it is important to understand the effect of EWB in these patients and whether it could improve postoperative recovery. Objective: To assess the association of EWB after FFF surgery with donor-site complications, length of stay, and discharge to home status. Design, Setting, and Participants: This retrospective cohort study took place at Massachusetts Eye and Ear, a single tertiary care institution in Boston, Massachusetts. A total of 152 patients who received head and neck reconstruction with a fibula osteocutaneous free flap between January 11, 2010, and August 11, 2022, were included. Exposure: EWB on postoperative day 1 vs non-EWB on postoperative day 2 or later. Main Outcomes and Measures: Patient characteristics, including demographic characteristics and comorbidities, surgical characteristics, donor-site complications, length of stay, and discharge disposition, were recorded. Descriptive statistics and multivariate logistic regressions were used to compute effect sizes and 95% CIs to compare postoperative outcomes in EWB and non-EWB groups. Results: A total of 152 patients (median [IQR] age, 63 [55-70] years; 89 [58.6%] male) were included. The median (IQR) time to postoperative weight-bearing was 3 (1-5) days. Among all patients, 14 (9.2%) had donor-site complications. EWB on postoperative day 1 was associated with shorter length of stay (adjusted odds ratio [AOR], 0.10; 95% CI, 0.02-0.60), increased rate of discharge to home (AOR, 7.43; 95% CI, 2.23-24.80), and decreased donor-site complications (AOR, 0.11; 95% CI, 0.01-0.94). Conversely, weight-bearing 3 or more days postoperatively was associated with an increased risk of pneumonia (AOR, 6.82; 95% CI, 1.33-34.99). Conclusions and Relevance: In this cohort study, EWB after FFF surgery was associated with shorter length of stay, increased rate of discharge to home, and decreased donor-site complications. These findings support the role of early mobilization to optimize postoperative recovery after FFF surgery.


Asunto(s)
Colgajos Tisulares Libres , Procedimientos de Cirugía Plástica , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Peroné , Soporte de Peso , Complicaciones Posoperatorias/epidemiología
14.
Risk Manag Healthc Policy ; 16: 2497-2504, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38024504

RESUMEN

One Health is increasingly recognized as an important approach for health systems, particularly with respect to strengthening prevention, detection and response to zoonotic and other emerging disease threats. While many global health security frameworks reference the importance of One Health, there are fewer existing methodologies, tools, and resources for supporting countries and other regional or sub-national authorities in systematically assessing their One Health capabilities. We describe here two methodologies, One Health Systems Assessment for Priority Zoonoses (OHSAPZ) and One Health Transboundary Assessment for Priority Zoonoses (OHTAPZ), which have been developed to assist with creating consensus lists of priority zoonotic diseases for cross-sectoral consideration; identification of current strengths and gaps in One Health communication and coordination between sectors (and, in the case of OHTAPZ, between countries); and the development and dissemination of prioritized recommendations for future capacity strengthening. Implemented to date in seven diverse countries in Africa and the Eastern Mediterranean regions, these tools provide a modular, flexible and easily adaptable approach to One Health systems assessment that can support national capacity strengthening, regional epidemic preparedness, and compliance with international frameworks.

15.
Laryngoscope ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37888781

RESUMEN

We describe a remote access thyroidectomy technique: robotic thyroidectomy via posterior neck approach using the Da Vinci single port (Sp) robotic system. This approach is feasible and safe in the Western population. Laryngoscope, 2023.

16.
J Pathol Inform ; 14: 100338, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860713

RESUMEN

In this paper, we consider the current and potential role of the latest generation of Large Language Models (LLMs) in medical informatics, particularly within the realms of clinical and anatomic pathology. We aim to provide a thorough understanding of the considerations that arise when employing LLMs in healthcare settings, such as determining appropriate use cases and evaluating the advantages and limitations of these models. Furthermore, this paper will consider the infrastructural and organizational requirements necessary for the successful implementation and utilization of LLMs in healthcare environments. We will discuss the importance of addressing education, security, bias, and privacy concerns associated with LLMs in clinical informatics, as well as the need for a robust framework to overcome regulatory, compliance, and legal challenges.

17.
bioRxiv ; 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37693470

RESUMEN

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons. Previous studies provided evidence that RBs fall into multiple subclasses; however, the number and molecular make up of these potential RB subtypes have not been well defined. Using a single-cell RNA sequencing (scRNA-seq) approach, we demonstrate that larval RBs in zebrafish fall into three, largely non-overlapping classes of neurons. We also show that RBs are molecularly distinct from trigeminal neurons in zebrafish. Cross-species transcriptional analysis indicates that one RB subclass is similar to a mammalian group of A-fiber sensory neurons. Another RB subclass is predicted to sense multiple modalities, including mechanical stimulation and chemical irritants. We leveraged our scRNA-seq data to determine that the fibroblast growth factor (Fgf) pathway is active in RBs. Pharmacological and genetic inhibition of this pathway led to defects in axon maintenance and RB cell death. Moreover, this can be phenocopied by treatment with dovitinib, an FDA-approved Fgf inhibitor with a common side effect of peripheral neuropathy. Importantly, dovitinib-mediated axon loss can be suppressed by loss of Sarm1, a positive regulator of neuronal cell death and axonal injury. This offers a molecular target for future clinical intervention to fight neurotoxic effects of this drug.

18.
Health Lit Res Pract ; 7(3): e154-e164, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37698848

RESUMEN

BACKGROUND: The definition of health literacy has recently expanded beyond the idea of individual skills to include the system and environment the individual interacts with to receive care, known as organizational health literacy (OHL). However, neither the prevalence of OHL nor the impact of OHL on individuals' perceptions of their health and healthcare have been examined in New York's Medicaid managed care population. OBJECTIVE: This study aimed to estimate the prevalence of organizational health literacy in the New York State (NYS) Medicaid Managed Care (MMC) program. METHODS: A brief measure to assess organizational health literacy was developed from responses to two questions in the 2018 NYS Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Generalized Estimating Equation models were developed to analyze the association between organizational health literacy and three aspects of perceptions of health and health care, controlling for demographic differences and clustering effects from health insurance plans. Missing data were handled using multiple imputation. KEY RESULTS: Among 3,598 members included in the study, 20% of the MMC members reported inadequate organizational health literacy. These members were more likely to be older, less educated, from racial and ethnic minority groups, and less fluent with English. They are more likely to have poorer self-reported health (odds ratio [OR] 1.49), lower perceived access to health care (OR 6.97), and lower satisfaction with their health care (OR 6.49) than members who did not report inadequate organizational health literacy. CONCLUSIONS: Our results suggest that a proportion of the NYS MMC population faces inadequate organizational health literacy, which can present a barrier to health care access and result in patients having a significantly poorer health care experience. Using an existing data source that is part of existing data collection allows for routine assessment of organizational health literacy, which can help inform health plans about areas for potential improvement. [HLRP: Health Literacy Research and Practice. 2023;7(3):e154-e164.].


PLAIN LANGUAGE SUMMARY: Our study looked at the impact of organizational health literacy on the perceptions of health and health care of NYS Medicaid Managed Care population. We used existing CAHPS questions to assess organizational health literacy and found that lower organizational health literacy led to worse perceptions of health and health care. This article illustrates an opportunity to demonstrate how organizational health literacy can be measured with annual CAHPS collections.


Asunto(s)
Etnicidad , Alfabetización en Salud , Estados Unidos , Humanos , Medicaid , Grupos Minoritarios , New York
19.
JBJS Rev ; 11(8)2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37549236

RESUMEN

The cost of surgical care accounts for almost one-third of all health care spending in the United States. Within health care spending, the operating room (OR) is one of the largest health care costs during a perioperative episode of care. Efficiency in the OR has been associated with increased productivity, safety, and quality of care. However, multiple sources of delays can contribute to inefficiency, and improving efficiency in the OR requires a systematic approach to identify and address each issue. We report on the case of a process improvement initiative implemented in a large academic institution to improve OR efficiency in outpatient orthopaedic cases, and we discuss the lessons learned through this program. Optimizing workflow in the OR requires a multidisciplinary team approach consisting of clinician leaders with common goals and open discussion regarding the needs of each team member, including circulating nurses, surgical nurses/technologists, and anesthesiologists. Our experience highlights the importance of practical, clinician-driven changes that are supported by administrative engagement, resources for staffing and equipment, and institutional flexibility, which are required to implement systemic changes to address and improve efficiency in the OR.


Asunto(s)
Quirófanos , Ortopedia , Humanos , Estados Unidos , Anestesiólogos
20.
PLOS Glob Public Health ; 3(7): e0002005, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37494334

RESUMEN

Continued emergence, re-emergence and spread of zoonotic diseases demonstrates the imperative need for multisectoral communication and joint coordination of disease detection and response. While there are existing international frameworks underpinning One Health capacity building for pandemic prevention and response, often guidance does not account for challenges faced by countries undergoing long-term conflict and sociopolitical instability. The purpose of this research was to identify Libya's laboratory and surveillance networks and routes of inter- and multisectoral communication and coordination for priority zoonotic diseases. The One Health Systems Assessment for Priority Zoonoses (OH-SAPZ) tool is an established methodology that was adapted and applied to the Libyan context to support prioritization of zoonotic diseases, development of systems map schematics outlining networks of communication and coordination, and analysis of operations for targeted capacity building efforts. Five zoonotic diseases were selected to undergo assessment: highly pathogenic avian influenza, brucellosis, Rift Valley fever, leishmaniasis and rabies. Through decisive acknowledgement of Libya's unique health setting, we mapped how patient and sample information is both communicated within and between the human, animal and environmental health sectors, spanning from local index case identification to international notification. Through our assessment we found strong communication within the public and animal health sectors, as well as existing multisectoral coordination on zoonotic disease response. However, local-level communication between the sectors is currently lacking. Due to the ongoing conflict, resources (financial and human) and access have been severely impacted, resulting in limited laboratory diagnostic capacity and discontinued disease prevention and control measures. We sought to identify opportunities to leverage existing operations for endemic diseases like brucellosis for emerging zoonotic threats, such as Rift Valley fever. Analysis of these operations and capabilities supports the development of targeted recommendations that address gaps and may be used as an implementation guide for future One Health capacity building efforts.

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