Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.451
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38727240

RESUMO

The current study evaluated the reliability and validity of a novel, performance-based banking task in 60 younger (18-34 years) and 60 older (50-85 years) adults. All participants completed the Telephone-based Daily Instrumental Activities of Living (T-DIAL) using interactive voice response technology to complete a series of mock actions with a financial institution via telephone. The T-DIAL showed strong inter-rater reliability and internal consistency. T-DIAL accuracy was significantly and independently related to better self-reported instrumental activities of daily living and executive functions at a large effect size. Findings from this study provided preliminary supportive evidence for the reliability and validity of the T-DIAL, which had robust associations with manifest everyday functioning and higher-order cognitive ability. Future work is needed on the psychometrics (e.g. test-retest reliability, normative standards), and construct validity (e.g. diagnostic accuracy) of the T-DIAL in neurocognitive disorders and under-served communities for whom remote evaluations might be particularly relevant.

2.
J Pediatr Intensive Care ; 13(1): 55-62, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38571989

RESUMO

Children with chronic critical illness (CCI) represent the sickest subgroup of children with medical complexity. In this article, we applied a proposed definition of pediatric CCI to assess point prevalence in medical, cardiovascular, and combined pediatric intensive care units (PICUs), screening all patients admitted to six academic medical centers in the United States on May 17, 2017, for pediatric CCI (PCCI) eligibility. We gathered descriptive data to understand medical complexity and resource needs of children with PCCI in PICUs including data regarding hospitalization characteristics, previous admissions, medical technology, and chronic multiorgan dysfunction. Descriptive statistics were used to characterize the study population and hospital data. The study cohort was divided between PICU-prolonged (stay > 14 days) and PICU-exposed (any time in PICU); comparative analyses were conducted. On the study day, 185 children met inclusion criteria, 66 (36%) PICU-prolonged and 119 (64%) PICU-exposed. Nearly all had home medical technology and most ( n = 152; 82%) required mechanical ventilation in the PICU. The PICU-exposed cohort mirrored the PICU-prolonged with a few exceptions as follows: they were older, had fewer procedures and surgeries, and had more recurrent hospitalizations. Most ( n = 44; 66%) of the PICU-prolonged cohort had never been discharged home. Children with PCCI were a sizable proportion of the unit census on the study day. We found that children with PCCI are a prevalent population in PICUs. Dividing the cohorts between PICU-prolonged and PICU-exposed helps to better understand the care needs of the PCCI population. Identifying and studying PCCI, including variables relevant to PICU-prolonged and PICU-exposed, could inform changes to PICU care models and training programs to better enable PICUs to meet their unique needs.

3.
Anal Methods ; 16(17): 2669-2677, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38623773

RESUMO

Analysis of mercury (Hg) in natural water samples has routinely been impractical in many environments, for example, artisanal and small-scale gold mines (ASGM), where difficult conditions make monitoring of harmful elements and chemicals used in the processes highly challenging. Current sampling methods require the use of hazardous or expensive materials, and so difficulties in sample collection and transport are elevated. To solve this problem, a solid-phase extraction-based method was developed for the sampling and preservation of dissolved Hg in natural water samples, particularly those found around ASGM sites. Recoveries of 85% ± 10% total Hg were obtained during 4 weeks of storage in refrigerated (4 °C, dark) and unrefrigerated (16 °C, dark) conditions, and from a representative river water spiked to 1 µg L-1 Hg2+, 94% ± 1% Hg recovery was obtained. Solid-phase extraction loading flow rates were tested at 2, 5, and 10 mL min-1 with no breakthrough of Hg, and sorbent stability showed no breakthrough of Hg up to 2 weeks after functionalisation. The method was deployed across five artisanal gold mines in Kakamega gold belt, Kenya, to assess Hg concentrations in mine shaft water, ore washing ponds, and river and stream water, including drinking water sources. In all waters, Hg concentrations were below the WHO guideline limit value of 6 µg L-1, but drinking water sources contained trace concentrations of up to 0.35 µg L-1 total Hg, which may result in negative health effects from long-term exposure. The SPE method developed and deployed here is a robust sampling method that can therefore be applied in future Hg monitoring, toxicology, and environmental work to provide improved data that is representative of total dissolved Hg in water samples.

4.
JAMA Cardiol ; 9(4): 357-366, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38416462

RESUMO

Importance: Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown. Objective: To develop a novel aortic stenosis PRS and compare its aortic stenosis risk estimation to established clinical risk factors. Design, Setting, and Participants: This was a longitudinal cohort study using data from the Million Veteran Program (MVP; 2011-2020), UK Biobank (2006-2010), and 6 Thrombolysis in Myocardial Infarction (TIMI) trials, including DECLARE-TIMI 58 (2013-2018), FOURIER (TIMI 59; 2013-2017), PEGASUS-TIMI 54 (2010-2014), SAVOR-TIMI 53 (2010-2013), SOLID-TIMI 52 (2009-2014), and ENGAGE AF-TIMI 48 (2008-2013), which were a mix of population-based and randomized clinical trials. Individuals from UK Biobank and the MVP meeting a previously validated case/control definition for aortic stenosis were included. All individuals from TIMI trials were included unless they had a documented preexisting aortic valve replacement. Analysis took place from January 2022 to December 2023. Exposures: PRS for aortic stenosis (developed using data from MVP and validated in UK Biobank) and other previously validated cardiovascular PRSs, defined either as a continuous variable or as low (bottom 20%), intermediate, and high (top 20%), and clinical risk factors. Main Outcomes: Aortic stenosis (defined using International Classification of Diseases or Current Procedural Terminology codes in UK Biobank and MVP or safety event data in the TIMI trials). Results: The median (IQR) age in MVP was 67 (57-73) years, and 135 140 of 147 104 participants (92%) were male. The median (IQR) age in the TIMI trials was 66 (54-78) years, and 45 524 of 59 866 participants (71%) were male. The best aortic stenosis PRS incorporated 5 170 041 single-nucleotide variants and was associated with aortic stenosis in both the MVP testing sample (odds ratio, 1.41; 95% CI, 1.37-1.45 per 1 SD PRS; P = 4.6 × 10-116) and TIMI trials (hazard ratio, 1.44; 95% CI, 1.27-1.62 per 1 SD PRS; P = 3.2 × 10-9). Among genetic and clinical risk factors, the aortic stenosis PRS performed comparably to most risk factors besides age, and within a given age range, the combination of clinical and genetic risk factors was additive, providing a 3- to 4-fold increased gradient of risk of aortic stenosis. However, the addition of the aortic stenosis PRS to a model including clinical risk factors only improved risk discrimination of aortic stenosis by 0.01 to 0.02 (C index in MVP: 0.78 with clinical risk factors, 0.79 with risk factors and aortic stenosis PRS; C index in TIMI: 0.71 with clinical risk factors, 0.73 with risk factors and aortic stenosis PRS). Conclusions: This study developed and validated 1 of the first aortic stenosis PRSs. While aortic stenosis genetic risk was independent from clinical risk factors and performed comparably to all other risk factors besides age, genetic risk resulted in only a small improvement in overall aortic stenosis risk discrimination beyond age and clinical risk factors. This work sets the stage for further development of an aortic stenosis PRS.


Assuntos
Estenose da Valva Aórtica , Infarto do Miocárdio , Humanos , Masculino , Idoso , Feminino , Estratificação de Risco Genético , Estudos Longitudinais , Predisposição Genética para Doença , Fatores de Risco , Estenose da Valva Aórtica/genética
5.
Clin Neuropsychol ; : 1-22, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414159

RESUMO

Introduction: Gay and bisexual men (GBM) account for the highest rates of incident infection with HIV in the U.S., and experience social, systemic barriers to accessing and engaging in healthcare services. Interacting with healthcare providers can be a complex process for some GBM with HIV disease. The current study examined the contributions of cognition and health literacy to perceived interactions with healthcare providers among GBM with HIV disease. Methods: The sample included 100 adults with HIV disease (ages 24-75) who identified as GBM. All participants completed the Dealing with Health Professionals subscale of the Beliefs Related to Medication Adherence survey, as well as the Cogstate neuropsychological battery, self-report measures of cognitive symptoms, and well-validated measures of health literacy. Results: Worse performance-based cognition and subjective cognitive symptoms were both associated with perceived difficulties dealing with healthcare providers, but these associations were fully mediated by lower health literacy. Conclusion: Health literacy may play a role in the association between poorer cognitive functioning and difficulties navigating healthcare interactions among GBM with HIV disease. Further studies are needed to determine whether cognitive approaches to enhancing the access, understanding, and use of health information in GBM with HIV disease improves healthcare interactions and outcomes.

6.
Circulation ; 149(12): 932-943, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38264923

RESUMO

BACKGROUND: The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. METHODS: We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. RESULTS: Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. CONCLUSIONS: The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Varfarina/efeitos adversos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Índice de Massa Corporal , Administração Oral , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Peso Corporal , Resultado do Tratamento
7.
Thyroid ; 34(3): 371-377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38010917

RESUMO

Background: ChatGPT, an artificial intelligence (AI) chatbot, is the fastest growing consumer application in history. Given recent trends identifying increasing patient use of Internet sources for self-education, we seek to evaluate the quality of ChatGPT-generated responses for patient education on thyroid nodules. Methods: ChatGPT was queried 4 times with 30 identical questions. Queries differed by initial chatbot prompting: no prompting, patient-friendly prompting, 8th-grade level prompting, and prompting for references. Answers were scored on a hierarchical score: incorrect, partially correct, correct, or correct with references. Proportions of responses at incremental score thresholds were compared by prompt type using chi-squared analysis. Flesch-Kincaid grade level was calculated for each answer. The relationship between prompt type and grade level was assessed using analysis of variance. References provided within ChatGPT answers were totaled and analyzed for veracity. Results: Across all prompts (n = 120 questions), 83 answers (69.2%) were at least correct. Proportions of responses that were at least partially correct (p = 0.795) and correct (p = 0.402) did not differ by prompt; responses that were correct with references did (p < 0.0001). Responses from 8th-grade level prompting were the lowest mean grade level (13.43 ± 2.86) and were significantly lower than no prompting (14.97 ± 2.01, p = 0.01) and prompting for references (16.43 ± 2.05, p < 0.0001). Prompting for references generated 80/80 (100%) of referenced medical publications within answers. Seventy references (87.5%) were legitimate citations, and 58/80 (72.5%) provided accurately reported information from the referenced publication. Conclusion: ChatGPT overall provides appropriate answers to most questions on thyroid nodules regardless of prompting. Despite targeted prompting strategies, ChatGPT reliably generates responses corresponding to grade levels well-above accepted recommendations for presenting medical information to patients. Significant rates of AI hallucination may preclude clinicians from recommending the current version of ChatGPT as an educational tool for patients at this time.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Inteligência Artificial , Educação de Pacientes como Assunto , Escolaridade , Internet
8.
J Perinatol ; 44(1): 1-11, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38097685

RESUMO

Artificial intelligence (AI) offers tremendous potential to transform neonatology through improved diagnostics, personalized treatments, and earlier prevention of complications. However, there are many challenges to address before AI is ready for clinical practice. This review defines key AI concepts and discusses ethical considerations and implicit biases associated with AI. Next we will review literature examples of AI already being explored in neonatology research and we will suggest future potentials for AI work. Examples discussed in this article include predicting outcomes such as sepsis, optimizing oxygen therapy, and image analysis to detect brain injury and retinopathy of prematurity. Realizing AI's potential necessitates collaboration between diverse stakeholders across the entire process of incorporating AI tools in the NICU to address testability, usability, bias, and transparency. With multi-center and multi-disciplinary collaboration, AI holds tremendous potential to transform the future of neonatology.


Assuntos
Lesões Encefálicas , Neonatologia , Sepse , Recém-Nascido , Humanos , Inteligência Artificial , Oxigenoterapia
9.
Head Neck ; 46(1): 212-217, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37933698

RESUMO

We depict an innovative surgical approach for sentinel lymph node biopsy (SLNB) in head and neck malignancies that utilizes both near-infrared (NIR) imaging with indocyanine green (ICG) dye and hand-held gamma probe intraoperatively to isolate and excise SLNs. Twenty-one patients presented to our institution with cutaneous melanoma, cutaneous squamous cell carcinoma (SCC), and oral cavity SCC tumors that met criteria for SLNB based on tumor depth and histology. The video offers a step-by-step approach for this technique along with descriptions of recommended equipment. Among 21 patients, two patients had positive SLNs on final pathology. One patient developed a local recurrence over an average of 16.2 months of follow-up (SD = 15.6). SLNB with ICG and radionucleotide co-localization may enhance the identification of sentinel nodes without compromising outcomes in the hands of surgeons well-versed in the technique.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Melanoma , Neoplasias Cutâneas , Humanos , Biópsia de Linfonodo Sentinela/métodos , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Melanoma/patologia , Verde de Indocianina , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Fluorescência , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Radioisótopos , Corantes , Linfonodos/patologia
10.
J Neonatal Perinatal Med ; 16(4): 717-723, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143379

RESUMO

BACKGROUND: We aimed to describe our experience with gabapentin use in infants admitted to our neonatal intensive care unit (NICU), including neurodevelopmental follow-up after discharge. METHODS: We performed a retrospective medical record review of infants prescribed gabapentin during admission to the University of Virginia NICU from 01/01/2015 to 04/30/2021. We report clinical characteristics including gabapentin indication, dosing and side-effects while in the NICU, discharge data, and assessments in outpatient developmental follow-up clinic. RESULTS: Gabapentin was prescribed to 104 infants (median gestational age 29 weeks, median postmenstrual age at initiation 41 weeks). Sixty-one percent of infants were male. The primary indication was irritability in 86%, and 67% were receiving at least one other neurosedative medication. Median maximum dose was 25 mg/kg/day (IQR 15-35 mg/kg/day) and 84% were discharged home on gabapentin. The majority required equipment at discharge (64% gastrostomy or nasogastric tube feeds, 54% supplemental oxygen or mechanical ventilation, and 40% both). At the first neurodevelopmental follow-up appointment, at least one area of delay was identified in 93% of infants and by 2 years corrected age 66% had a diagnosis of global developmental delay. CONCLUSIONS: NICU patients treated with gabapentin often require complex post-discharge care and require close neurodevelopmental follow up.


Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Lactente , Humanos , Masculino , Feminino , Gabapentina/uso terapêutico , Estudos Retrospectivos , Assistência ao Convalescente , Alta do Paciente
12.
BMJ Open ; 13(11): e075840, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949625

RESUMO

OBJECTIVE: Poor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been evaluated objectively. We sought to determine the extent to which oral medication properties thought to be influential translate into lower objectively-measured adherence. DESIGN: Retrospective cohort study. SETTING: US nationwide commercial claims database, 2016-2019. PARTICIPANTS: Among patients initiating first-line hypertension, diabetes or hyperlipidaemia treatment based on clinical guidelines, we measured pill size, shape, colour and flavouring, number of pills/day and fixed-dose combination status as properties. OUTCOME MEASURES: Outcomes included discontinuation after the first fill (ie, never filling again over a minimum of 1-year follow-up) and long-term non-adherence (1-year proportion of days covered <0.80). We estimated associations between each property and outcomes, by therapeutic class (eg, statins), with multivariable logistic regression. RESULTS: Across 604 323 patients, 14.6% discontinued after filling once (ie, were non-persistent), and 54.0% were non-adherent over 1-year follow-up. Large pill size was associated with non-adherence, except for thiazides (eg, metformin adjusted OR (aOR): 1.12, 95% CI: 1.06 to 1.18). Greater pill burden was associated with a higher risk of non-adherence across all classes (eg, metformin aOR: 1.58, 95% CI: 1.53 to 1.64 for two pills/day). Taking less than one pill/day was also associated with higher risk of non-adherence and non-persistence (eg, non-persistence statin aOR: 1.29, 95% CI: 1.20 to 1.38). Pill shape, colour, flavouring and combination status were associated with mixed effects across classes. CONCLUSIONS: Pill burden and pill size are key properties affecting adherence for almost all classes; others, like size and combination, could modestly affect medication adherence. Clinical interventions could screen patients for potential intolerance to medication and potentially implement more convenient dosing schedules.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Metformina , Humanos , Estados Unidos , Estudos Retrospectivos , Hipertensão/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adesão à Medicação , Metformina/uso terapêutico
13.
MethodsX ; 11: 102466, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37954969

RESUMO

Two of the groups most impacted by microplastics (MPs) are zooplankton and fish larvae, either through MPs ingestion or absorption. Although there has been an increase of studies focusing on MPs ingestion by these organisms, there is still no standardized methodology for the quantification of MPs present in plankton. For example, some reagents normally used to digest plankton and recover MPs appear adversely to affect some plastic characteristics. This can potentially lead to underestimating the amount and types of MPs present in the organisms analyzed. Hence, this work aimed to optimize a methodology to quantify MPs present in plankton, namely zooplankton and fish larvae, and ensuring MPs integrity. Hence, the planktonic organism tissues were digested using 30% (v/v) H2O2 solution at different temperatures and incubation periods while preserving the integrity and polymer characteristics of 13 types of MPs. MPs' characteristics were register before and after the tests, by visual inspection and Fourier Transform Infrared Spectroscopy (FTIR) analysis, to evaluate the integrity and features of MPs. With this methodology, MPs recovery was above 85% for all types of plastic tested. The proposed methodology is a rapid protocol, with a maximum of 7 h of incubation, that ensures simultaneously the full digestion of the organism tissues and the complete preservation of all the plastic characteristics, namely color, size and polymer type.•A methodology was optimized to quantify microplastics present in zooplankton (copepods, chaetognaths and fish larvae).•Thirteen types of microplastics (fibers and fragments of different polymers) were used to test the efficiency of the methodology ensuring the maintenance of the integrity of plastics.•With this methodology, microplastic recovery was above 85% for all the types of microplastic tested and no changes in their characteristics were observed.

14.
Proc Natl Acad Sci U S A ; 120(48): e2315503120, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37988464

RESUMO

Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin 1ß (IL1ß) and interleukin 18 (IL18). Thereby, Gasdermins have been implicated in various immune responses against cancer and infectious diseases such as acute Salmonella Typhimurium (S.Tm) gut infection. However, to date, we lack a comprehensive functional assessment of the different Gasdermins (GSDMA-E) during S.Tm infection in vivo. Here, we used epithelium-specific ablation, bone marrow chimeras, and mouse lines lacking individual Gasdermins, combinations of Gasdermins or even all Gasdermins (GSDMA1-3C1-4DE) at once and performed littermate-controlled oral S.Tm infections in streptomycin-pretreated mice to investigate the impact of all murine Gasdermins. While GSDMA, C, and E appear dispensable, we show that GSDMD i) restricts S.Tm loads in the gut tissue and systemic organs, ii) controls gut inflammation kinetics, and iii) prevents epithelium disruption by 72 h of the infection. Full protection requires GSDMD expression by both bone-marrow-derived lamina propria cells and intestinal epithelial cells (IECs). In vivo experiments as well as 3D-, 2D-, and chimeric enteroid infections further show that infected IEC extrusion proceeds also without GSDMD, but that GSDMD controls the permeabilization and morphology of the extruding IECs, affects extrusion kinetics, and promotes overall mucosal barrier capacity. As such, this work identifies a unique multipronged role of GSDMD among the Gasdermins for mucosal tissue defense against a common enteric pathogen.


Assuntos
Gasderminas , Infecções por Salmonella , Animais , Camundongos , Infecções por Salmonella/prevenção & controle , Salmonella typhimurium , Inflamação , Células Epiteliais , Inflamassomos
15.
Clin Case Rep ; 11(10): e7987, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37830070

RESUMO

Aberrant migration of parathyroid glands from their embryologic origin may result in undescended parathyroid glands. We present a case of an ectopic parathyroid adenoma at the level of the pyriform sinus. A 41-year-old female was evaluated for primary hyperparathyroidism. Following non-localizing ultrasound and planar sestamibi imaging, the patient underwent SPECT/CT and 4-D computed tomography demonstrating evidence of an ectopic parathyroid adenoma. The surgical approach was modified based on the location. Following extirpation, PTH fell from 80 to 16 pg/mL, and the 15-min post-excision level remained stable at 14pg/mL, indicating a biochemical cure. While rare, undescended parathyroid adenoma should be considered when preoperative imaging fails to identify a target adenoma or after unsuccessful surgery. The combined use of 99m Tc-MBI or 4D CT and other anatomical scans may improve diagnostic accuracy. Due to the potential need to perform a second incision to conduct a four-gland exploration, preoperative patient discussion regarding surgical risks may differ from that of a standard parathyroidectomy.

16.
J Cell Biol ; 222(12)2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37737955

RESUMO

Peroxisomes are organelles involved in many metabolic processes including lipid metabolism, reactive oxygen species (ROS) turnover, and antimicrobial immune responses. However, the cellular mechanisms by which peroxisomes contribute to bacterial elimination in macrophages remain elusive. Here, we investigated peroxisome function in iPSC-derived human macrophages (iPSDM) during infection with Mycobacterium tuberculosis (Mtb). We discovered that Mtb-triggered peroxisome biogenesis requires the ESX-1 type 7 secretion system, critical for cytosolic access. iPSDM lacking peroxisomes were permissive to Mtb wild-type (WT) replication but were able to restrict an Mtb mutant missing functional ESX-1, suggesting a role for peroxisomes in the control of cytosolic but not phagosomal Mtb. Using genetically encoded localization-dependent ROS probes, we found peroxisomes increased ROS levels during Mtb WT infection. Thus, human macrophages respond to the infection by increasing peroxisomes that generate ROS primarily to restrict cytosolic Mtb. Our data uncover a peroxisome-controlled, ROS-mediated mechanism that contributes to the restriction of cytosolic bacteria.


Assuntos
Macrófagos , Mycobacterium tuberculosis , Peroxissomos , Espécies Reativas de Oxigênio , Humanos , Citosol , Macrófagos/microbiologia , Mycobacterium tuberculosis/genética , Espécies Reativas de Oxigênio/metabolismo , Sistemas de Secreção Tipo VII
17.
Am J Perinatol ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37774747

RESUMO

OBJECTIVE: This study aimed to better understand the interpersonal influences on a pregnant individual's decision of how to treat nausea and vomiting during pregnancy using a qualitative approach. STUDY DESIGN: A semistructured interview guide was developed to assess pregnancy symptoms, decision-making regarding treating nausea, and interpersonal influences on treatment decisions. Interviews were conducted with 17 individuals enrolled in a neuroimaging and behavioral study of prenatal exposure to cannabis who used medication and/or cannabis to treat symptoms associated with pregnancy. RESULTS: Interviews revealed four groups of stakeholders who influenced participant decision-making: medical providers, partners, family, and friends. Influence was categorized as either positive, negative, neutral, or absent (if not discussed or participant chose not to disclose). Those in the medication group reported only positive or neutral feedback from friends, family, partners, and providers. In contrast, the cannabis group participants reported positive feedback from friends, mixed feedback from family and partners, and negative feedback from providers, which was often felt to be stigmatizing. Many in the cannabis group also reported varying feedback from different medical providers. While the cannabis group frequently reported eliciting feedback from friends, family, and partners, the medication group often did not. CONCLUSION: Medication group participants reported entirely positive feedback from providers and often did not mention any feedback at all from partners, family, and friends. Cannabis group participants reported much more varied feedback, both positive and negative, from a variety of interpersonal contacts and sometimes decided to conceal their treatment choice after receiving or fearing negative feedback. We recommend further research into the health outcomes of pregnant patients who chose not to discuss their treatment decisions with providers, family, partners, or friends. We also suggest further study of possible reasons behind a lack of disclosure, including fear of stigma and/or legal consequences. KEY POINTS: · Providers, partners, family, friends gave feedback.. · Medication group got positive feedback.. · Cannabis group stigmatized by providers.. · Cannabis group got mixed feedback..

18.
Cancer Med ; 12(18): 18882-18888, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37706634

RESUMO

BACKGROUND: Opioids are a mainstay in pain control for oncologic surgery. The objective of this systematic review is to evaluate the associations of perioperative opioid use with overall survival (OS) and disease-free survival (DFS) in patients with resectable head and neck cancer (HNC). METHODS: A systematic review of PubMed, SCOPUS, and CINAHL between 2000 and 2022 was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies investigating perioperative opioid use for patients with HNC undergoing surgical resection and its association with OS and DFS were included. RESULTS: Three thousand three hundred seventy-eight studies met initial inclusion criteria, and three studies representing 562 patients (intraoperative opioids, n = 463; postoperative opioids, n = 99) met final exclusion criteria. One study identified that high intraoperative opioid requirement in oral cancer surgery was associated with decreased OS (HR = 1.77, 95% CI 0.995-3.149) but was not an independent predictor of decreased DFS. Another study found that increased intraoperative opioid requirements in treating laryngeal cancer was demonstrated to have a weak but statistically significant inverse relationship with DFS (HR = 1.001, p = 0.02) and OS (HR = 1.001, p = 0.02). The last study identified that patients with chronic opioid after resection of oral cavity cancer had decreased DFS (HR = 2.7, 95% CI 1.1-6.6) compared to those who were not chronically using opioids postoperatively. CONCLUSION: An association may exist between perioperative opioid use and OS and DFS in patients with resectable HNC. Additional investigation is required to further delineate this relationship and promote appropriate stewardship of opioid use with adjunctive nonopioid analgesic regimens.

19.
Mol Cell ; 83(15): 2621-2623, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37541218

RESUMO

Red blood cell rupture (hemolysis) activates innate immunity and inflammation by releasing heme. Sundaram et al.1 implicate the immune sensor NLRP12 in hemolytic disease, showing that it controls necrotic cell death induction in response to heme combined with pathogen-associated molecules.


Assuntos
Heme , Moléculas com Motivos Associados a Patógenos , Humanos , Heme/metabolismo , Inflamação/metabolismo , Imunidade Inata , Hemólise , Necrose , Morte Celular , Peptídeos e Proteínas de Sinalização Intracelular
20.
Hist Psychol ; 26(4): 283-313, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37561482

RESUMO

From 1929 until 1972, the Alberta Eugenics Board (the Board) recommended that 4,739 individuals be sterilized. The original 1928 act that legalized eugenic sterilization stipulated that the surgery itself required the consent of the individual or their caregiver; however, in 1937, the Alberta government removed the consent requirement for such cases where the Board determined individual patients to be "mental defectives." By analyzing published reports, case histories, medical journals, and primary sources from the Board, we situate the concept of "mental defective" in a historical context to clarify the Board's diagnostic process. By analyzing how the Board found individuals to be "mental defectives," we challenge a previous historiographic assumption that intelligence tests played a critical or defining role in this diagnostic process. We argue that the notion of the "mental defective" used by the Board had a long history before the advent of intelligence testing and eugenic thought. This history helps to explain how and why the Board relied extensively on the broader examination of behavior, social status, and physical appearance as core evidence in the diagnosis of "mental defect." Intelligence tests were certainly important as they shed light on an individual's academic ability. However, this alone was only one part of "mentality." Defects of mentality were understood to be broad and multifactorial, and included difficult, if not impossible, to measure attributes such as personality, emotionality, and morality. Further research should incorporate the concept of mentality in the history of psychology, testing, and eugenics. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...