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1.
Front Immunol ; 15: 1400036, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835762

RESUMO

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.


Assuntos
Artrite Juvenil , Monócitos , Transcriptoma , Humanos , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Feminino , Monócitos/imunologia , Monócitos/metabolismo , Perfilação da Expressão Gênica , Adolescente , Adulto , Criança , Masculino , Inflamação/genética , Inflamação/imunologia
2.
J Hypertens ; 42(7): 1109-1132, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690949

RESUMO

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.


Assuntos
Hipertensão Induzida pela Gravidez , Feminino , Humanos , Gravidez , Anti-Hipertensivos/uso terapêutico , Europa (Continente) , Hipertensão Induzida pela Gravidez/terapia , Complicações Cardiovasculares na Gravidez/terapia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Sociedades Médicas/normas , Guias de Prática Clínica como Assunto
3.
Front Psychiatry ; 15: 1369783, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476614

RESUMO

Introduction: It is well known that chronic opioid use disorder is associated with alterations in gastrointestinal (GI) function that include constipation, reduced motility, and increased bacterial translocation due to compromised gut barrier function. These signs of disrupted GI function can be associated with alterations in the gut microbiome. However, it is not known if long-access opioid self-administration has effects on the gut microbiome. Methods: We used 16S rRNA gene sequencing to investigate the gut microbiome in three independent cohorts (N=40 for each) of NIH heterogeneous stock rats before onset of long-access heroin self-administration (i.e., naïve status), at the end of a 15-day period of self-administration, and after post-extinction reinstatement. Measures of microbial α- and ß-diversity were evaluated for all phases. High-dimensional class comparisons were carried out with MaAsLin2. PICRUSt2 was used for predicting functional pathways impacted by heroin based on marker gene sequences. Results: Community α-diversity was not altered by heroin at any of the three phases by comparison to saline-yoked controls. Analyses of ß-diversity showed that the heroin and saline-yoked groups clustered significantly apart from each other using the Bray-Curtis (community structure) index. Heroin caused significant alterations at the ASV level at the self-administration and extinction phases. At the phylum level, the relative abundance of Firmicutes was increased at the self-administration phase. Deferribacteres was decreased in heroin whereas Patescibacteria was increased in heroin at the extinction phase. Potential biomarkers for heroin emerged from the MaAsLin2 analysis. Bacterial metabolomic pathways relating to degradation of carboxylic acids, nucleotides, nucleosides, carbohydrates, and glycogen were increased by heroin while pathways relating to biosynthesis of vitamins, propionic acid, fatty acids, and lipids were decreased. Discussion: These findings support the view that long access heroin self-administration significantly alters the structure of the gut microbiome by comparison to saline-yoked controls. Inferred metabolic pathway alterations suggest the development of a microbial imbalance favoring gut inflammation and energy expenditure. Potential microbial biomarkers and related functional pathways likely invoked by heroin self-administration could be targets for therapeutic intervention.

4.
Adv Pharmacol ; 99: 61-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467489

RESUMO

The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as "bath salts". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes.


Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Humanos , Catinona Sintética , Metanfetamina/efeitos adversos , Anfetamina , Estimulantes do Sistema Nervoso Central/efeitos adversos
5.
Curr Hypertens Rep ; 26(6): 247-258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512586

RESUMO

PURPOSE OF REVIEW: This comprehensive review provides an in-depth exploration of the complex relationship between obesity and preeclampsia (PE) and emphasizes the clinical implications of this association. It highlights the crucial role of screening tools in assessing individual risk and determining the need for additional antenatal care among women with obesity. The review investigates various markers for identifying the risk of developing PE, while emphasizing the significance of interventions such as exercise, weight management, and a balanced diet in reducing the incidence of preeclampsia and improving outcomes for both mother and fetus. RECENT FINDINGS: Actually, there is a global pandemic of obesity, particularly among women of childbearing age and pregnant women. PE, which is characterized by maternal hypertension, proteinuria, and complications, affects 2-4% of pregnancies worldwide, posing significant risks to maternal and perinatal health. Women with obesity face an elevated risk of developing PE due to the systemic inflammation resulting from excess adiposity, which can adversely affect placental development. Adipose tissue, rich in proinflammatory cytokines and complement proteins, contributes to the pathogenesis of PE by promoting the expression of antiangiogenic factors in the mother. This review emphasizes the need for appropriate screening, interventions, and a holistic approach to reduce the incidence of preeclampsia and enhance maternal-fetal well-being, thus providing valuable insights into the multifaceted association between obesity and PE.


Assuntos
Obesidade , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Obesidade/complicações , Fatores de Risco
7.
Artigo em Espanhol | LILACS-Express | LILACS, BNUY | ID: biblio-1556980

RESUMO

En diciembre de 2019, en Wuhan, China, se detectaron los primeros casos de SARS-CoV-2. En Uruguay, desde el 16 de marzo de 2020 se suspendieron las actividades de enseñanza, deportivas y espectáculos públicos. Varios países reportaron una marcada disminución de las visitas a urgencias. Algunos niños presentaron enfermedades ocasionales o descompensaciones de enfermedades crónicas, consultando en forma tardía con el riesgo que ello implica. El objetivo de este trabajo es realizar una descripción de las consultas tardías durante la pandemia. Se realizó un estudio multicéntrico y descriptivo entre el 13 de marzo y el 29 de julio de 2020. Se definió consulta tardía como los ingresos por injurias agudas con más de 6 horas de evolución, fiebre mayor a 72 horas de evolución, dificultad respiratoria con más de 12 horas de evolución, síntomas agudos, como dolor abdominal, de más de 24 horas de evolución, síntomas de más de 12 horas de evolución en niños con enfermedades crónicas que determinaron descompensación e ingreso. Se incluyeron 27 centros. Se registraron un total de 34.260 consultas en urgencia, se incluyeron 189 niños para el estudio. El promedio de edad fue de 6 años; 17 pacientes requirieron ingreso a unidad de cuidados intensivos (UCI). Predominó la apendicitis entre los diagnósticos al alta. Esta investigación puso en evidencia la existencia de consultas tardías en nuestro país. Esto contribuye a ponderar el impacto negativo de la pandemia en la población pediátrica.


Summary: In December 2019, the first cases of SARS-CoV-2 were detected in Wuhan. In Uruguay, since March 16, teaching, sports and public entertainment activities were suspended. Several countries reported a marked decrease in emergency room visits. Some children presented occasional illnesses or decompensations from chronic illnesses, consulting late with the risk that this implies. The objective of the work is to make a description of late consultations during the pandemic. A multicenter and descriptive study was carried out between March 13 and July 29, 2020. "Late consultation" was defined as admissions for: Acute injuries with more than 6 hours of evolution, fever greater than 72 hours of evolution, difficulty respiratory disease with more than 12 hours of evolution, acute symptoms such as abdominal pain of more than 24 hours of evolution, symptoms of more than 12 hours of evolution in children with chronic diseases that determined decompensation and admission. 27 centers were included. A total of 34260 emergency consultations were registered, 189 children were included for the study. The average age was 6 years. 17 patients required admission to the ICU. Appendicitis predominated among the diagnoses at discharge. This research revealed the existence of late consultations in our country. This helps to weigh the negative impact of the pandemic on the pediatric population.


Em dezembro de 2019, em Wuhan, foram detectados os primeiros casos de SARS-CoV-2. No Uruguai, desde 16 de março, as atividades de ensino, esporte e entretenimento público foram suspensas. Vários países relataram uma diminuição acentuada nas visitas ao pronto-socorro. Algumas crianças apresentavam doenças ocasionais ou descompensações de doenças crônicas, consultando tardiamente os riscos que isso implica. O objetivo do trabalho é fazer uma descrição das consultas tardias durante a pandemia. Um estudo multicêntrico e descritivo foi realizado entre 13 de março e 29 de julho de 2020. Consulta tardia foi definida como internações por: Lesões agudas com mais de 6 horas de evolução, febre maior que 72 horas de evolução, dificuldade respiratória com mais de 12 horas de evolução, sintomas agudos como dor abdominal com mais de 24 horas de evolução, sintomas com mais de 12 horas de evolução em crianças com doenças crônicas que determinaram descompensação e internação. 26 centros foram incluídos. Um total de 34.260 consultas de emergência foram registradas, 189 crianças foram incluídas no estudo. A idade média era de 6 anos. 17 pacientes necessitaram de internação na UTI. Apendicite predominou entre os diagnósticos na alta. Esta pesquisa revelou a existência de consultas tardias em nosso país. Isso ajuda a pesar o impacto negativo da pandemia na população pediátrica.

8.
Front Immunol ; 14: 1251034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868981

RESUMO

Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions. Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.


Assuntos
Artrite Reumatoide , Monócitos , Humanos , Feminino , Monócitos/metabolismo , Transcriptoma , Inflamação/genética , Inflamação/metabolismo , Perfilação da Expressão Gênica
9.
P R Health Sci J ; 42(3): 241-245, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37709682

RESUMO

OBJECTIVE: In complicated parapneumonic effusion or Empyema, approximately 25% of patients require surgical intervention which can be associated with a mortality risk of almost 20%. However, the use combination of rt-tPA and DNase in elderly patients with prohibitive surgical risk has improved outcomes. The main goal of our study is to highlight the utility of intrapleural thrombolysis in patients with prohibitive risk for surgery. METHODS: A retrospective record review study of patients (n=23) with complicated parapneumonic pleural effusion or empyema treated with tPA and DNase from January 1st of 2015 to March 18th, 2019 at VACHCS. Data collected to describe the outcome of intrapleural thrombolytics included demographic, pleural fluid analysis, surgical risk assessment, diagnosis and initiation treatment day, doses, chest imaging, drainage rate, chest tube size and average days in place, inflammatory markers, microbiology, antibiotics, and complications. RESULTS: Only 21.7% of patients were considered surgical candidates. Seventy-four percent had a 30-day post-surgical mortality risk of > 2.5% using the National Surgery Office (NSO) risk calculator. Post-operative inpatient stay was 99.7% and estimated post operative ICU stay average was >80%. Primary outcome (pleural drainage improvement) obtained in 73.9%. Most common serious complications included sepsis (52.2%) and nonserious was residual hydropneumothorax (47.8%). CONCLUSION: This study demonstrates that administration of intrapleural thrombolytics through a percutaneous pleural catheter achieved successful drainage safely and without the need for surgical interventions in a selected group of advanced age, elderly patients with pleural infections who were deemed to be high surgical risk.


Assuntos
Empiema , Derrame Pleural , Idoso , Humanos , Estudos Retrospectivos , Derrame Pleural/etiologia , Derrame Pleural/terapia , Fibrinolíticos , Desoxirribonucleases
10.
Sci Rep ; 13(1): 13754, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612353

RESUMO

Cocaine is a highly addictive psychostimulant drug of abuse that constitutes an ongoing public health threat. Emerging research is revealing that numerous peripheral effects of this drug may serve as conditioned stimuli for its central reinforcing properties. The gut microbiota is emerging as one of these peripheral sources of input to cocaine reward. The primary objective of the present study was to determine how cocaine HCl and methylenedioxypyrovalerone, both of which powerfully activate central reward pathways, alter the gut microbiota. Cocaine methiodide, a quaternary derivative of cocaine that does not enter the brain, was included to assess peripheral influences on the gut microbiota. Both cocaine congeners caused significant and similar alterations of the gut microbiota after a 10-day course of treatment. Contrary to expectations, the effects of cocaine HCl and MDPV on the gut microbiota were most dissimilar. Functional predictions of metabolic alterations caused by the treatment drugs reaffirmed that the cocaine congeners were similar whereas MDPV was most dissimilar from the other two drugs and controls. It appears that the monoamine transporters in the gut mediate the effects of the treatment drugs. The effects of the cocaine congeners and MDPV on the gut microbiome may form the basis of interoceptive cues that can influence their abuse properties.


Assuntos
Estimulantes do Sistema Nervoso Central , Cocaína , Microbioma Gastrointestinal , Catinona Sintética , Cocaína/farmacologia
11.
Semin Arthritis Rheum ; 63: 152247, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37595510

RESUMO

OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.


Assuntos
Artrite Juvenil , Osteoporose , Humanos , Feminino , Adulto Jovem , Adulto , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico por imagem , Densidade Óssea , Rádio (Anatomia) , Tomografia Computadorizada por Raios X , Tíbia/diagnóstico por imagem , Absorciometria de Fóton
13.
Dermatol Pract Concept ; 13(2)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196281

RESUMO

INTRODUCTION: Skin cancer remains a global public health burden. Dermoscopy is a useful technique that aids in early detection and increases diagnostic accuracy with adequate training. However, dermoscopy is not uniformly taught to residents worldwide. Dermoscopy training in Latin American dermatology residency programs has not been explored. OBJECTIVES: To assess current dermoscopy training among dermatology residency programs in Latin America (eg training modalities, preferred/most effective modalities per residents, diseases/pathologies taught). METHODS: Cross-sectional survey distributed via e-mail between March and May 2021. Chief residents from Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Guatemala, Mexico, Panama, and Uruguay were invited to participate. RESULTS: 81 chief residents completed the questionnaire (81/126, 64.2%). Seventy-two percent of programs had an established dermoscopy curriculum, with dedicated hours of training varying greatly by program. Institutions commonly utilized sessions with "unknown" dermoscopy images and direct teaching by experts in the clinical setting as supplements to lectures, also described by residents as most effective. The most commonly taught methods included pattern analysis (74.1%), the two-step algorithm (61.7%), and the ABCD rule (59.3%). Almost all respondents reported desiring additional training during residency and believe that dermoscopy training should be a requirement to graduate from residency. CONCLUSIONS: This study highlights a preliminary look into current landscape in dermoscopy training among selected Latin American dermatology residency programs, demonstrating room for improvement and standardization in dermoscopic education and training. Our results serve as a baseline reference and provide valuable information to guide future educational initiatives incorporating successful teaching strategies (eg. spaced education/repetition, flipped classroom model) used in dermatology and other fields.

14.
Mar Pollut Bull ; 188: 114715, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36780788

RESUMO

Coastal social-ecological systems in the Caribbean are affected by pelagic Sargassum spp. influxes and decomposition, but most satellite monitoring efforts focus on offshore waters. We developed a method to detect and spatial-temporally assess sargassum accumulations and their decaying stages along the shoreline and nearshore waters. A multi-predictor Random Forest model combining Sentinel-2 MultiSpectral Instrument reflectance bands and several vegetation, seaweed, water, and water quality indices was developed within the online Google Earth Engine platform. The model achieved 97 % overall accuracy and identified both fresh and decomposing sargassum, as well as the Sargassum-brown-tide generated from decomposing sargassum. We identified three hotspots of sargassum accumulation in La Parguera, Puerto Rico and found that sargassum was present every month in at least one of its forms during the entire time series (September 2015-January 2022). This research provides information to understand sargassum impacts and areas where mitigation efforts need to focus.


Assuntos
Sargassum , Porto Rico , Ferramenta de Busca , Índias Ocidentais , Ecossistema
15.
Adv Biol (Weinh) ; 7(11): e2200289, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36650949

RESUMO

Inhabitants of urban areas are constantly exposed to light at night, which is an important environmental factor leading to circadian disruption. Streetlights filtering light through the windows and night dim light lamps are common sources of dim light at night (DLAN). The female population is susceptible to circadian disruption. The present study is aimed to determine the impact of DLAN on female Wistar rats circadian rhythms, metabolism, reproductive physiology, and behavior. After 5 weeks of DLAN exposure daily, oscillations in activity and body temperature of female rats are abolished. DLAN also decreases nocturnal food ingestion, which results in a diminishment in total food consumption. These alterations in the temporal organization of the body are associated with a significant decrease in melatonin plasmatic levels, reproductive disruptions, decreased exploration times, and marked anhedonia. This study highlights the importance of avoiding exposure to light at night, even at low intensities, to maintain the circadian organization of physiology, and denotes the great necessity of increasing the studies in females since the sexual dimorphism within the effects of desynchronizing protocols has been poorly studied.


Assuntos
Atividade Motora , Fotoperíodo , Ratos , Feminino , Animais , Atividade Motora/fisiologia , Ratos Wistar , Ritmo Circadiano/fisiologia , Luz
16.
Arch Dermatol Res ; 315(5): 1401-1403, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36372843

RESUMO

Biologics are the most effective treatment for moderate-to-severe psoriasis. Insurance approval and need for prior authorization continue to be a barrier to care for many patients with psoriasis and psoriatic arthritis. We sought to determine whether race/ethnicity, insurance type, and provider specialty affect biologic approval times. Records from the University of Miami Health System were reviewed, and 101 patients were included. Need for a prior authorization was significantly associated with long waits (p = 2.4 × 10-5). We did not identify a significant difference in wait times between non-Hispanic Whites and non-Whites. The average wait time for biologic approval for Whites was 29.7 days and for non-Whites was 27.2 days. Biologics were approved the same day for 23.7% of HMO carriers, 11.5% of PPO carriers, 63% of Medicare carriers, and 40% of Medicaid carriers (p < 0.001). There was no difference in the biologic type prescribed based on insurance type. Medicaid (p < 0.05) and the need for prior authorization (p = 2.4 × 10-5) significantly predicted approval wait time in our multilinear regression model. Patients with Medicare had the shortest wait time with a mean of 7.3 days. Medicaid patients waited a mean of 11.3 days. Private insurance patients waited the longest, regardless of whether they had a PPO (37 days) or HMO (41.3 days).


Assuntos
Artrite Psoriásica , Produtos Biológicos , Psoríase , Idoso , Humanos , Estados Unidos , Medicare , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico
17.
J Invest Dermatol ; 143(3): 456-469.e8, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36174713

RESUMO

The prognosis for patients with metastatic melanoma (MM) involving distant organs is grim, and treatment resistance is potentiated by tumor-initiating cells (TICs) that thrive under hypoxia. MM cells, including TICs, express a unique glycome featuring i-linear poly-N-acetyllactosamines through the loss of I-branching enzyme, ß1,6 N-acetylglucosaminyltransferase 2. Whether hypoxia instructs MM TIC development by modulating the glycome signature remains unknown. In this study, we explored hypoxia-dependent alterations in MM glycome‒associated genes and found that ß1,6 N-acetylglucosaminyltransferase 2 was downregulated and a galectin (Gal)-8-ligand axis, involving both extracellular and cell-intrinsic Gal-8, was induced. Low ß1,6 N-acetylglucosaminyltransferase 2 levels correlated with poor patient outcomes, and patient serum samples were elevated for Gal-8. Depressed ß1,6 N-acetylglucosaminyltransferase 2 in MM cells upregulated TIC marker, NGFR/CD271, whereas loss of MM cell‒intrinsic Gal-8 markedly lowered NGFR and reduced TIC activity in vivo. Extracellular Gal-8 bound preferentially to i-linear poly-N-acetyllactosamines on N-glycans of the TIC marker and prometastatic molecule CD44, among other receptors, and activated prosurvival factor protein kinase B. This study reveals the importance of hypoxia governing the MM glycome by enforcing i-linear poly-N-acetyllactosamine and Gal-8 expression. This mechanistic investigation also uncovers glycome-dependent regulation of pro-MM factor, NGFR, implicating i-linear poly-N-acetyllactosamine and Gal-8 as biomarkers and therapeutic targets of MM.


Assuntos
Galectinas , N-Acetilglucosaminiltransferases , Humanos , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Ligantes
19.
Arch. pediatr. Urug ; 93(2): e205, dic. 2022. graf, tab
Artigo em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1383652

RESUMO

En marzo de 2020 se confirma el primer caso de enfermedad por coronavirus en Uruguay, recomendándose un confinamiento social. La atención sanitaria se redujo a servicios de urgencia y emergencia (SE). Objetivo: analizar las características de las consultas pediátricas en los SE del subsector público y privado en Uruguay, durante los primeros 4 meses de la pandemia por SARS-CoV-2. Metodología: estudio descriptivo, retrospectivo, multicéntrico. Resultados: participaron 23 SE de todas las regiones del país. Período 1 prepandemia: 14/03/19-29.07.19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (desciende 73%). Hospitalizaciones desde el SE: período 1 n= .6649 (tasa 5,5%). Período 2: n=2.948 (tasa 9,5%). Diagnósticos período 1: infección respiratoria aguda (IRA) alta 39.892 (33%), IRA baja 86.56 (7%), trauma menor 8.651 (7%), gastroenteritis 8.044 (6,6%), crisis asmática/CBO 7.974 (6,5%), lesiones 4.389 (3,6%), dolor abdominal 3.528 (3%), problemas de salud mental 859 (0,7%), convulsiones 758 (0,7%), patología social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma menor 2.759 (8%), lesiones 2.652 (8%), dolor abdominal 1.494 (4,5%), gastroenteritis 1.296 (4%), asma/CBO 1.095 (3,3%), IRA baja 700 (2,1%), patología social 522 (1,6%), problemas de salud mental 471 (1,4%), convulsiones 408 (1,2%). Conclusiones: en los primeros meses de la pandemia hubo una reducción sostenida y significativo de consultas pediátricas en los SE. No hubo aumento en frecuencia absoluta de ninguno de los diagnósticos. Se registró un descenso histórico de las IRA bajas y las hospitalizaciones por esta causa en todo el país. Mantener una vigilancia de las consultas en los SE permitiría identificar e intervenir oportunamente si se produjeran cambios o situaciones de riesgo hasta el momento no detectadas.


In March 2020 the first case of coronavirus disease was confirmed in Uruguay, and lockdown was recommended. Health care services were reduced to Urgency and Emergency Services (ES). Objectives: to analyze the epidemiological characteristics of pediatric visits to the ES of the public and private subsector in Uruguay, during the first 4 months of the SARS-CoV-2 pandemic. Methods: descriptive, retrospective. Results: 23 institutions participated. 2 periods were considered: 1) pre-pandemic, 03/14/19 to 07/29/19, 2) 03/14/20 to 07/29/20. Visits: period 1: n=121,116 (< 15 years), period 2: n=33.099 (73% decrease). Hospital admissions: period 1: n=6,649 (rate 5.5). Period 2: n=2.948 (rate 9,5). Diagnoses period 1: High acute respiratory infection 39,892 (33%), low acute respiratory infection 8,656 (7%), minor trauma 8,651 (7%), gastroenteritis 8,044 (6,6%), asthmatic crisis/CBO 7.974 (6,5%), injuries 4,389 (3,6%), abdominal pain (3,528) 3%, mental health problems 859 (0.7%), seizures 758 (0.7%), social pathology 678 (0.5% ). 2020 diagnoses: high acute respiratory infection 5.168 (16%), minor trauma 2,759 (8%), injuries 2,652 (8%), abdominal pain 1,494 (4.5%), gastroenteritis 1,296 (4%), asthma/CBO 1,095 (3,3%), low acute respiratory infection 700 (2,1%), social pathology 522 (1,6%), mental health problems 471 (1,4%), seizures 408 (1,2%). Conclusions: in the first months of the pandemic there was a sustained and significant reduction in pediatric consultations in ES. There was no increase in absolute frequency of any of the diagnoses. There was a historical decrease in low respiratory infections and hospitalizations due to this cause in the whole country. Maintaining a surveillance of the visits in the ES would enable practitioners to identify and take action in case of changes or previously undetected risk situations.


Em março de 2020, foi confirmado o primeiro caso de doença por coronavírus no Uruguai, recomendando o confinamento. A assistência à saúde foi reduzida a serviços de urgência e emergência (SE). Objetivo: analisar as características das consultas pediátricas no SE do subsetor público e privado no Uruguai, durante os primeiros 4 meses da pandemia de SARS-CoV-2. Metodologia: estudo descritivo, retrospectivo, multicêntrico. Resultados: participaram 23 SEs de todas as regiões do país. Período pré-pandemia 1: 14/03/19-29/07/19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (redução de 73%) . Internações da SE: período 1 n= 0,6649 (taxa 5,5%). Período 2: n=2.948 (taxa de 9,5%). Diagnósticos do período 1: infecção respiratória aguda alta (IRA) 39.892 (33%), LRA baixa 86,56 (7%), trauma menor 8.651 (7%), gastroenterite 8.044 (6,6%), crise asmática/CBO 7.974 (6, 5% ), lesões 4.389 (3,6%), dor abdominal 3.528 (3%), problemas de saúde mental 859 (0,7%), convulsões 758 (0,7%), patologia social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma leve 2.759 (8%), lesões 2.652 (8%), dor abdominal 1.494 (4,5%), gastroenterite 1.296 (4%), asma/CBO 1.095 (3, 3%), IRA baixa 700 (2,1%), patologia social 522 (1,6%), problemas de saúde mental 471 (1,4%), convulsões 408 (1,2%). Conclusões: nos primeiros meses da pandemia houve uma redução sustentada e significativa das consultas pediátricas no SE. Não houve aumento na frequência absoluta de nenhum dos diagnósticos. Foi registrado um decréscimo histórico de IRAs baixas e internações por essa causa em todo o país. A manutenção de uma vigilância das consultas no SE permitiria identificar e intervir atempadamente nos casos de alterações ou situações de risco que até agora não tinham sido detectadas.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Saúde da Criança/estatística & dados numéricos , Cuidados Médicos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pandemias , COVID-19/epidemiologia , Uruguai/epidemiologia , Estudos Retrospectivos , Estudo Multicêntrico , Setor Público , Setor Privado , Distribuição por Idade e Sexo
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