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1.
Laryngoscope ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895915

RESUMO

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

2.
JAMA Otolaryngol Head Neck Surg ; 149(12): 1066-1073, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796485

RESUMO

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors. Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy. Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023. Exposure: Tracheotomy. Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique. Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82). Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.


Assuntos
Obesidade Mórbida , Otolaringologia , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Traqueotomia , Otorrinolaringologistas , Estudos Retrospectivos , Anticoagulantes
3.
Mar Environ Res ; 186: 105925, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36857940

RESUMO

Molluscs are among the organisms affected by ocean acidification (OA), relying on carbon for shell biomineralization. Metabolic and environmental sourcing are two pathways potentially affected by OA, but the circumstances and patterns by which they are altered are poorly understood. From previous studies, mollusc shells grown under OA appear smaller in size, brittle and thinner, suggesting an important alteration in carbon sequestration. However, supplementary feeding experiments have shown promising results in offsetting the negative consequences of OA on shell growth. Our study compared carbon uptake by δ13C tracing and deposition into mantle tissue and shell layers in Magallana gigas and Mytilus species, two economically valuable and common species. After subjecting the species to 7.7 pH, +2 °C seawater, and enhanced feeding, both species maintain shell growth and metabolic pathways under OA without benefitting from extra feeding, thus, showing effective acclimation to rapid and short-term environmental change. Mytilus spp. increases metabolic carbon into the calcite and environmental sourcing of carbon into the shell aragonite in low pH and high temperature conditions. Low pH affects M. gigas mantle nitrogen isotopes maintaining growth. Calcite biomineralization pathway differs between the two species and suggests species-specific response to OA.


Assuntos
Mytilus , Ostreidae , Animais , Biomineralização , Água do Mar/química , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Carbonato de Cálcio/metabolismo , Carbono/metabolismo , Dióxido de Carbono/análise , Exoesqueleto/química
4.
Ann Surg ; 277(5): e1138-e1142, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35001037

RESUMO

OBJECTIVE: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge. SUMMARY OF BACKGROUND DATA: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation. METHODS: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge. RESULTS: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation. CONCLUSIONS: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube.


Assuntos
Traqueostomia , Traqueotomia , Humanos , Estudos Retrospectivos , Remoção de Dispositivo , Obesidade
5.
Arch Dermatol Res ; 315(4): 807-813, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36319702

RESUMO

INTRODUCTION: Alopecia areata (AA) is the most common form of immune-mediated hair loss. Studies have begun to establish the most frequent comorbid diseases of AA; however, results have been inconsistent with few prospective studies. METHODS: A total of 63,692 women in the Nurses' Health Study, 53-80 years, were prospectively followed from 2002 to 2014 to determine whether history of immune-mediated disease was associated with AA risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) for AA in relation to immune-mediated conditions were computed using Cox proportional hazard models, adjusted for AA risk factors. RESULTS: 133 AA cases were identified during follow-up. Personal history of any immune-mediated disease was associated with increased AA risk (HR 1.72, 95% CI 1.24-2.37). History of systemic lupus erythematosus (HR 5.43, 95% CI 2.11-13.97), multiple sclerosis (HR 4.10, 95% CI 1.40-11.96), vitiligo (HR 3.13, 95% CI 1.08-9.10), psoriasis (HR 2.01, 95% CI 1.00-4.03), hypothyroidism (HR 1.88, 95% CI 1.30-2.71), and rheumatoid arthritis (HR 1.66, 95% CI 1.09-2.52) were associated with increased AA risk. History of inflammatory bowel disease or Graves' disease/hyperthyroidism was not significantly associated with AA risk. CONCLUSIONS: In this prospective study, personal history of immune-mediated diseases either individually or overall was associated with increased AA risk.


Assuntos
Alopecia em Áreas , Doença de Graves , Humanos , Feminino , Estudos Prospectivos , Alopecia em Áreas/epidemiologia , Fatores de Risco
6.
Society ; 59(6): 660-671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370325

RESUMO

QAnon, a group of conspiracy theorists dedicated to the overthrow of the deep state and the facilitation of the rapture, has been growing in strength and prominence since its inception in 2017. Originally started as an anonymous post on a message board, the collective has increased in membership, geographic footprint, and ideological reach. QAnon initiates have also expanded their repertoire of tactics, evolving from online chatter to rallies and, finally, to violent attacks, leading law enforcement to opine that the group may incite incidents of domestic terrorism. Although this outcome is possible, predictions of this kind have less merit unless supported by systematic analysis of the evidence. This essay attempts to address this need by providing an empirically grounded prediction of the future of QAnon. Specifically, it summarizes the results of comparative case analyses, which consists of examining groups and collectives that are comparable to QAnon on key factors and applying their trajectories to QAnon. Case comparisons indicate that QAnon may continue to grow in membership size and regional presence. In addition, QAnon members may persist in their use of violence, leading to an increase in the number and severity of their attacks.

7.
Cell Cycle ; 21(10): 1103-1119, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35240916

RESUMO

Clear cell renal cell carcinoma (CC-RCC) remains one of the most deadly forms of kidney cancer despite recent advancements in targeted therapeutics, including tyrosine kinase and immune checkpoint inhibitors. Unfortunately, these therapies have not been able to show better than a 16% complete response rate. In this study we evaluated a cyclin-dependent kinase inhibitor, Dinaciclib, as a potential new targeted therapeutic for CC-RCC. In vitro, Dinaciclib showed anti-proliferative and pro-apoptotic effects on CC-RCC cell lines in Cell Titer Glo, Crystal Violet, FACS-based cell cycle analysis, and TUNEL assays. Additionally, these responses were accompanied by a reduction in phospho-Rb and pro-survival MCL-1 cell signaling responses, as well as the induction of caspase 3 and PARP cleavage. In vivo, Dinaciclib efficiently inhibited primary tumor growth in an orthotopic, patient-derived xenograft-based CC-RCC mouse model. Importantly, Dinaciclib targeted both CD105+ cancer stem cells (CSCs) and CD105- non-CSCs in vivo. Moreover, normal cell lines, as well as a CC-RCC cell line with re-expressed von-Hippel Lindau (VHL) tumor suppressor gene, were protected from Dinaciclib-induced cytotoxicity when not actively dividing, indicating an effective therapeutic window due to synthetic lethality of Dinaciclib treatment with VHL loss. Thus, Dinaciclib represents a novel potential therapeutic for CC-RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Óxidos N-Cíclicos , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Quinases Ciclina-Dependentes/genética , Feminino , Humanos , Indolizinas , Neoplasias Renais/patologia , Masculino , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Piridínio , Mutações Sintéticas Letais , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
8.
Front Cell Dev Biol ; 10: 837406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178392

RESUMO

The nucleus harbours numerous protein subdomains and condensates that regulate chromatin organization, gene expression and genomic stress. A novel nuclear subdomain that is formed following exposure of cells to excess fatty acids is the nuclear lipid droplet (nLD), which is composed of a neutral lipid core surrounded by a phospholipid monolayer and associated regulatory and lipid biosynthetic enzymes. While structurally resembling cytoplasmic LDs, nLDs are formed by distinct but poorly understood mechanisms that involve the emergence of lipid droplets from the lumen of the nucleoplasmic reticulum and de novo lipid synthesis. Luminal lipid droplets that emerge into the nucleoplasm do so at regions of the inner nuclear membrane that become enriched in promyelocytic leukemia (PML) protein. The resulting nLDs that retain PML on their surface are termed lipid-associated PML structures (LAPS), and are distinct from canonical PML nuclear bodies (NB) as they lack key proteins and modifications associated with these NBs. PML is a key regulator of nuclear signaling events and PML NBs are sites of gene regulation and post-translational modification of transcription factors. Therefore, the subfraction of nLDs that form LAPS could regulate lipid stress responses through their recruitment and retention of the PML protein. Both nLDs and LAPS have lipid biosynthetic enzymes on their surface suggesting they are active sites for nuclear phospholipid and triacylglycerol synthesis as well as global lipid regulation. In this review we have summarized the current understanding of nLD and LAPS biogenesis in different cell types, their structure and composition relative to other PML-associated cellular structures, and their role in coordinating a nuclear response to cellular overload of fatty acids.

9.
Laryngoscope ; 131(11): 2441-2447, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33493366

RESUMO

OBJECTIVE/HYPOTHESIS: Elderly individuals account for one-third of all hospitalizations. The goal of this study was to evaluate the prevalence of dysphagia in elderly patients admitted to a tertiary care center. It also sought to investigate how dysphagia is identified, how it covaries with malnutrition and other conditions, and how it impacts hospital stay. STUDY DESIGN: Case Series. METHODS: A retrospective chart review was performed. All patients >65 years admitted to a tertiary care center in January and February 2016 were included. Patients with primary psychiatric diagnoses and patients with upper aerodigestive tract malignancy or surgery were excluded. RESULTS: A total of 655 patients were identified. Mean age was 76.6 years. Twenty-four percent (155 patients) had dysphagia while 43% (282 patients) had malnutrition. Thirteen percent (84 patients) had both dysphagia and malnutrition. Fifty percent of patients who had malnutrition were seen by speech language pathology (SLP). One hundred percent of malnourished patients that saw SLP were identified as having dysphagia. Three hundred and eighty-two patients (58%) were seen by the dietician but not by SLP. Multiple logistic regression indicated that the presence of dysphagia was positively associated with age, presence of malnutrition, admission to either cardiology or neurology service as compared to medicine service, and history of stroke. CONCLUSIONS: One-quarter of elderly patients admitted to our tertiary care center had dysphagia. Dysphagia, especially when linked with malnutrition, has poorer outcomes and increased healthcare costs. Our data suggests a possible disconnect between malnutrition diagnosis and dysphagia identification. This is an important area of intervention that has the potential to improve the treatment and outcomes of these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2441-2447, 2021.


Assuntos
Transtornos de Deglutição/epidemiologia , Desnutrição/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Transtornos de Deglutição/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Desnutrição/economia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/economia , Centros de Atenção Terciária/estatística & dados numéricos
10.
J Biotechnol ; 326: 52-60, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33373626

RESUMO

Protein normalization of western blots has relied upon housekeeping proteins which exhibit signal saturation and varied cellular expression level variations. These issues can produce spurious results leading to erroneous conclusions. A superior method to protein normalization using housekeeping proteins is Total Protein Normalization, a method now recognized as the gold standard for quantitative westerns. Total Protein Normalization requires that all proteins on a membrane be stained or labeled uniformly, imaged, and then analyzed for total protein. It is important that such a normalization process not interfere with typical immunodetection methods, fits within existing western workflows, and exhibits a linear relationship of signal intensity to protein load under all experimental conditions. Here we report that we developed a new reagent enabling Total Protein Normalization, and we demonstrate its superior protein normalization capabilities through analysis of target proteins in different cell backgrounds. These data illustrate how housekeeping proteins exhibit signal saturation, yield erroneous normalization data, and display sample-to-sample variations averaging 48.2 % overall. Signal intensities obtained using our new method show a linear relationship to protein sample load, thus providing accurate protein normalization with an overall average variation of 7.7 %.


Assuntos
Proteínas , Western Blotting
11.
South Med J ; 113(11): 549-552, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33140107

RESUMO

The purpose of this literature review was to further explore gynecological care and contraceptive use in women with cerebral palsy. We address barriers to pelvic examinations for cervical cancer screenings and current contraceptive methods in severely debilitated patients with cerebral palsy.


Assuntos
Paralisia Cerebral/complicações , Comportamento Contraceptivo , Doenças dos Genitais Femininos/prevenção & controle , Comportamento Contraceptivo/psicologia , Comportamento Contraceptivo/estatística & dados numéricos , Feminino , Neoplasias dos Genitais Femininos/prevenção & controle , Humanos
12.
Bioorg Med Chem ; 28(18): 115659, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32828426

RESUMO

The botulinum neurotoxin (BoNT) is the most lethal protein known to man causing the deadly disease botulinum. The neurotoxin, composed of a heavy (HC) and light (LC) chain, work in concert to cause muscle paralysis. A therapeutic strategy to treat individuals infected with the neurotoxin is inhibiting the catalytic activity of the BoNT LC. We report the synthesis, inhibition study and computational docking analysis of novel small molecule BoNT/A LC inhibitors. A structure activity relationship study resulted in the discovery of d-isoleucine functionalized with a hydroxamic acid on the C-terminal and a biphenyl with chlorine at C- 2 connected by a sulfonamide linker at the N-terminus. This compound has a measured IC50 of 0.587 µM for the BoNT/A LC. Computational docking analysis indicates the sulfonamide linker adopts a geometry that is advantageous for binding to the BoNT LC active site. In addition, Arg363 is predicted to be involved in key binding interactions with the scaffold in this study.


Assuntos
Toxinas Botulínicas Tipo A/antagonistas & inibidores , Isoleucina/química , Sulfonamidas/síntese química , Sítios de Ligação , Clostridium botulinum/metabolismo , Humanos , Ácidos Hidroxâmicos/química , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade , Sulfonamidas/farmacologia
13.
Surg Neurol Int ; 11: 97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494376

RESUMO

BACKGROUND: The aim of the study was to present a case of mixed olfactory neuroblastoma (ONB) and carcinoma, an extremely rare tumor with only a few cases in the published literature. CASE DESCRIPTION: An otherwise healthy 27-year-old male presented with sinus complaints, headache, and unilateral eye discharge. Imaging and endoscopy revealed a mass presumed to represent a juvenile nasopharyngeal angiofibroma. Unexpectedly, the final pathology report revealed high grade mixed ONB and carcinoma. This tumor is the sixth and youngest documented patient with mixed ONB and carcinoma. CONCLUSION: Physicians should remain vigilant for the possibility of malignancy in their approach to nasal cavity masses, even in young otherwise healthy patients. Careful review of the immunohistopathology should also be taken, as mixed olfactory tumors such as these are aggressive, rare entities that require multidisciplinary oncologic care.

14.
Mol Biol Cell ; 31(10): 1047-1059, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186954

RESUMO

CTP:phosphocholine cytidylyltransferase-alpha (CCTα) and CCTß catalyze the rate-limiting step in phosphatidylcholine (PC) biosynthesis. CCTα is activated by association of its α-helical M-domain with nuclear membranes, which is negatively regulated by phosphorylation of the adjacent P-domain. To understand how phosphorylation regulates CCT activity, we developed phosphosite-specific antibodies for pS319 and pY359+pS362 at the N- and C-termini of the P-domain, respectively. Oleate treatment of cultured cells triggered CCTα translocation to the nuclear envelope (NE) and nuclear lipid droplets (nLDs) and rapid dephosphorylation of pS319. Removal of oleate led to dissociation of CCTα from the NE and increased phosphorylation of S319. Choline depletion of cells also caused CCTα translocation to the NE and S319 dephosphorylation. In contrast, Y359 and S362 were constitutively phosphorylated during oleate addition and removal, and CCTα-pY359+pS362 translocated to the NE and nLDs of oleate-treated cells. Mutagenesis revealed that phosphorylation of S319 is regulated independently of Y359+S362, and that CCTα-S315D+S319D was defective in localization to the NE. We conclude that the P-domain undergoes negative charge polarization due to dephosphorylation of S319 and possibly other proline-directed sites and retention of Y359 and S362 phosphorylation, and that dephosphorylation of S319 and S315 is involved in CCTα recruitment to nuclear membranes.


Assuntos
Colina-Fosfato Citidililtransferase/metabolismo , Gotículas Lipídicas/metabolismo , Membrana Nuclear/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/metabolismo , Colina/metabolismo , Colina-Fosfato Citidililtransferase/química , Células HeLa , Humanos , Modelos Biológicos , Ácido Oleico/metabolismo , Fosforilação , Transporte Proteico , Ratos
15.
J Am Acad Dermatol ; 83(4): 1064-1070, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279016

RESUMO

BACKGROUND: Epidemiologic studies on the association between race and alopecia areata (AA) are limited. OBJECTIVE: To characterize racial differences of AA in the United States. METHODS: Cross-sectional study of self-registered AA patients and noncases in the National Alopecia Areata Registry (NAAR). We evaluated odds of AA and its subtypes for 5 ethnic/racial groups using logistic regression. A sex-stratified analysis and a sensitivity analysis among dermatologist-confirmed cases were also performed. RESULTS: We identified 9340 AA patients and 2064 noncases. Compared with whites, African Americans had greater odds of AA (odds ratio, 1.77; 95% confidence interval, 1.37-2.28) and Asians had lower odds (odds ratio, 0.40; 95% confidence interval, 0.32-0.50) of AA. The results were consistent in AA subtypes, dermatologist-confirmed cases, and by sex. LIMITATIONS: Residual confounding due to limited number of covariates. Recall or recruitment bias not representative of the entire disease spectrum. Also, outcome misclassification was possible because not all AA cases in the registry were confirmed by dermatologists. CONCLUSION: Our findings suggest higher odds of AA in African Americans and lower odds in Asians compared with whites. Future studies examining racial disparity in AA from clinical and genetic perspectives are warranted for a better understanding of the disease pathogenesis.


Assuntos
Alopecia em Áreas/etnologia , Asiático/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto , Idoso , Asma/etnologia , Comorbidade , Estudos Transversais , Dermatite Atópica/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Rinite Alérgica/etnologia , Doenças da Glândula Tireoide/etnologia , Estados Unidos/epidemiologia , Adulto Jovem
16.
J Am Acad Dermatol ; 82(3): 661-665, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31404570

RESUMO

BACKGROUND: Associations between gluten intake and psoriasis, psoriatic arthritis, and atopic dermatitis are poorly understood. OBJECTIVE: To determine whether increased gluten intake is associated with incident psoriasis, psoriatic arthritis, and atopic dermatitis. METHODS: Cohort studies among women in Nurses' Health Study II. Food frequency questionnaires were used to calculate gluten content of participants' diet every 4 years (1991-2015 for psoriatic disease, 1995-2013 for atopic dermatitis). Disease outcomes were assessed by self-report and subsequently validated. Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between gluten intake (quintiles) and psoriasis, psoriatic arthritis, and atopic dermatitis. RESULTS: We included 85,185 participants in the psoriasis analysis, 85,324 in the psoriatic arthritis analysis, and 63,443 in the atopic dermatitis analysis. Increased gluten intake was not associated with any of the outcomes (all P for trend >.05). Comparing highest and lowest gluten intake quintiles, the multivariable hazard ratios (95% confidence intervals) were 1.15 (0.98-1.36) for psoriasis, 1.12 (0.78-1.62) for psoriatic arthritis, and 0.91 (0.66-1.25) for atopic dermatitis. LIMITATIONS: No assessment of a strictly gluten-free diet. CONCLUSIONS: Our findings do not support the amount of dietary gluten intake as a risk factor for psoriasis, psoriatic arthritis, or atopic dermatitis in adult women.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite Psoriásica/etiologia , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Dieta/efeitos adversos , Glutens/efeitos adversos , Psoríase/epidemiologia , Psoríase/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Medição de Risco , Fatores de Risco , Estados Unidos
17.
Small GTPases ; 11(1): 32-38, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-28632992

RESUMO

The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. We recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation. Increased expression and activity of both HIFs and ROCK1 occurs in many types of cancer supporting the potential therapeutic role of ROCK inhibitors beyond CC-RCC. We also discuss future research required to establish prognostic markers to predict tumor response to ROCK inhibitors.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia
18.
Angew Chem Int Ed Engl ; 59(4): 1532-1536, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31693792

RESUMO

The ophiobolin sesterterpenes are notable plant pathogens which have recently elicited significant chemical and biological attention because of their intriguing carbogenic frameworks, reactive functionalities, and emerging anticancer profiles. Reported herein is a total synthesis of (+)-6-epi-ophiobolin A in 14 steps, a task which addresses construction of the synthetically challenging spirocyclic tetrahydrofuran motif as well as several other key stereochemical problems. This work demonstrates a streamlined synthetic platform to complex ophiobolins leveraging disparate termination modes of a radical polycyclization cascade for divergent elaboration and functionalization.


Assuntos
Produtos Biológicos/síntese química , Sesterterpenos/síntese química , Produtos Biológicos/química , Sesterterpenos/química
19.
PLoS One ; 14(9): e0222956, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560711

RESUMO

OBJECTIVE: The passive leg raising (PLR) maneuver has become standard practice in fluid resuscitation. We aim to investigate the precision and consistency of the PLR for determining fluid responsiveness in critically ill patients and healthy volunteers using bioreactance non-invasive cardiac output monitoring (NiCOM™, Cheetah Medical, Inc., Newton Center, Massachusetts, USA). METHODS: This study is prospective, single-center, observational cohort with repeated measures in critically ill patients admitted to the medical intensive care unit and healthy volunteers at a tertiary academic medical center. Three cycles of PLR were performed, each at 20-30 minutes apart. Fluid responsiveness was defined as a change in stroke volume index (ΔSVI) > 10% with each PLR as determined by NiCOM™. Precision was the variability in ΔSVI after the 3 PLR's, and determined by range, average deviation and standard deviation. Consistency was the same fluid responsiveness determination of "Yes" (ΔSVI > 10%) or "No" (ΔSVI ≤ 10%) for all 3 PLR's. RESULTS: Seventy-five patients and 25 volunteers were enrolled. In patients, the precision was range of 17.2±13.3%, average deviation 6.5±4.0% and standard deviation 9.0±5.2%; and for volunteers, 17.4±10.3%, 6.6±3.8% and 9.0±6.7%, respectively. There was no statistical difference in the precision measurements between patients and volunteers. Forty-nine (65.3%) patients vs. twenty-four (96.0%) volunteers had consistent results, p < 0.01. Among those with consistent results, twenty-four (49.0%) patients and 24 (100%) volunteers were fluid responsive. CONCLUSIONS: The precision and consistency of determining ΔSVI with NiCOM™ after PLR may have clinical implication if ΔSVI > 10% is the absolute cutoff to determine fluid responsiveness.


Assuntos
Estado Terminal/terapia , Hidratação , Monitorização Fisiológica/métodos , Posicionamento do Paciente/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Unidades de Terapia Intensiva , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico/fisiologia , Resultado do Tratamento , Adulto Jovem
20.
Cornea ; 38(2): 177-182, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30615600

RESUMO

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.


Assuntos
Doenças da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Idoso , Idoso de 80 Anos ou mais , Doenças da Córnea/fisiopatologia , Perda de Células Endoteliais da Córnea/etiologia , Feminino , Rejeição de Enxerto/patologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Acuidade Visual/fisiologia
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