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1.
J Infect Prev ; 25(3): 85-88, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38584711

RESUMO

Objective: To describe a multicenter outbreak of R. pickettii that occurred in a large number of critically ill patients in a city in Colombia, during the COVID-19 pandemic. Methods: In April 2021, the National Institute for Food and Drug Surveillance (INVIMA) reported an outbreak of R. pickettii infection associated with contaminated intravenous medications. The Municipal Health Department began collecting data for all cases identified by the hospitals and the results of microbiological studies. Medical records and death certificates of included cases were reviewed. Results: Between March and May 2021, 66 cases of R. pickettii bloodstream infections from nine hospitals were documented. The median age of the patients was 60 years (IQR 51-72), and most of them had comorbidities (78.8%), mainly arterial hypertension and diabetes mellitus. At the time of the R. pickettii bloodstream infection, 89.4% had COVID-19, 86.4% were on mechanical ventilation, and 98.5% were receiving corticosteroids. The overall mortality was 81.8%. Nearly 60% of the deaths were related to R. pickettii bloodstream infections. R. pickettii was identified in the cultures from intravenous medications. Conclusions: This large multicenter outbreak caused by intravenous medications contaminated with R. pickettii mainly affected critically ill COVID-19 patients. Mortality was high and largely related to R. pickettii bloodstream infection.

2.
J Clin Immunol ; 44(4): 87, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578402

RESUMO

We present a case study of a young male with a history of 22q11.2 deletion syndrome (22qDS), diagnosed with systemic capillary leak syndrome (SCLS) who presented with acute onset of diffuse anasarca and sub-comatose obtundation. We hypothesized that his co-presentation of neurological sequelae might be due to blood-brain barrier (BBB) susceptibility conferred by the 22q11.2 deletion, a phenotype that we have previously identified in 22qDS. Using pre- and post-intravenous immunoglobulins (IVIG) patient serum, we studied circulating biomarkers of inflammation and assessed the potential susceptibility of the 22qDS BBB. We employed in vitro cultures of differentiated BBB-like endothelial cells derived from a 22qDS patient and a healthy control. We found evidence of peripheral inflammation and increased serum lipopolysaccharide (LPS) alongside endothelial cells in circulation. We report that the patient's serum significantly impairs barrier function of the 22qDS BBB compared to control. Only two other cases of pediatric SCLS with neurologic symptoms have been reported, and genetic risk factors have been suggested in both instances. As the third case to be reported, our findings are consistent with the hypothesis that genetic susceptibility of the BBB conferred by genes such as claudin-5 deleted in the 22q11.2 region promoted neurologic involvement during SCLS in this patient.


Assuntos
Síndrome de Vazamento Capilar , Síndrome de DiGeorge , Humanos , Masculino , Criança , Síndrome de Vazamento Capilar/diagnóstico , Barreira Hematoencefálica , Células Endoteliais , Permeabilidade , Inflamação
3.
Thyroid ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661525

RESUMO

BACKGROUND: The National Institutes of Health (NIH) is the major funding agency for biomedical research in the United States. To initiate a scholarly dialog about research and career development in the thyroid field, here we reviewed recent trends in NIH funding for this area. We used the RePORT (Research Portfolio Online Reporting Tool) database to estimate the level of NIH extramural support during 2013-2022 (number of active grants/year, and $ amount/year weighed by the total number of active grants/year and $ amount/year), provided by the NIH to the thyroid field. We determined that in 2013 the NIH supported 140 grants/year, totaling almost $50 million/year, the majority in the form of R01 grants. Within the thyroid field, support was evenly split between thyroid cancer and thyroid hormone metabolism and action subareas. In the subsequent years (2014-2022), the total number of active grants peaked at 150/year ($55 million) in 2014 but progressively decreased to about 100 active grants/year ($30 million) in 2022. This trend occurred while the NIH budget increased from $29 to $46 billion/year. Globally, the number of thyroid-related publications increased by 70% during the study period, and the fractional contribution of several countries remained relatively stable, except for China which increased by 600%. Remarkably, the fraction of thyroid-related publications in the USA sponsored by the NIH decreased from 5.5% to 3.1% of the global number. CONCLUSION: These results constitute a very concerning scenario for research and education in the thyroid field. We appeal that the NIH, the professional societies in endocrinology and thyroidology, and all other relevant stakeholders such as thyroid-related professionals and thyroid patients engage in further discussions to identify the root causes of this trend and implement an action plan to stabilize and eventually reverse this situation.

4.
Sensors (Basel) ; 24(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38544004

RESUMO

Due to the continuously growing demands from high-added-value sectors such as aerospace, e-mobility or biomedical bound-abrasive technologies are the key to achieving extreme requirements. During grinding, energy is rapidly dissipated as heat, generating thermal fields on the ground part which are characterized by high temperatures and very steep gradients. The consequences on the ground part are broadly known as grinding burn. Therefore, the measurement of workpiece temperature during grinding has become a critical issue. Many techniques have been used for temperature measurement in grinding, amongst which, the so-called grindable thermocouples exhibit great potential and have been successfully used in creep-feed grinding operations, in which table speed is low, and therefore, temperature gradients are not very steep. However, in conventional grinding operations with faster table speeds, as most industrial operations are, the delay in the response of the thermocouple results in large errors in the maximum measured value. In this paper, the need for accurate calibration of the response of grindable thermocouples is studied as a prior step for signal integration to correct thermal inertia. The results show that, if the raw signal is directly used from the thermocouples, the deviation in the maximum temperature with respect to the theoretical model is over 200 K. After integration using the calibration constants obtained for the ground junction, the error can be reduced to 93 K even for feed speeds as high as 40 m/min and below 20 K for lower feed speeds. The main conclusion is that, following the proposed procedure, maximum grinding temperatures can be effectively measured using grindable thermocouples even at high values of table speed.

5.
Hum Immunol ; : 110787, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38480040

RESUMO

INTRODUCTION: Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. METHODS: A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. RESULTS: A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. CONCLUSION: The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.

7.
J Clin Med ; 13(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256664

RESUMO

BACKGROUND: Metal-on-metal (M-M) total hip arthroplasty (THA) has shown adverse reactions to metal debris, abnormal soft-tissue reactions, and high blood metal ion levels. This study aims to: (1) assess whether the toxicity of high levels of ions is related to altered oxidative stress and (2) evaluate tribological factors related to increased blood levels of chromium (Cr) and cobalt (Co) ions. METHODS: A cross-sectional analytical descriptive study was conducted on 75 patients. A total of 25 underwent M-M THA, 25 ceramic-on-metal (C-M) THA, and 25 were on the THA waiting list. Ion metallic levels in blood, oxidative stress, physical activity, and implant position were compared. RESULTS: In the M-M group, Co and Cr levels were significantly higher than those found in the C-M group and the control group (p < 0.01). We found no differences in terms of oxidative stress between the groups. Also, we did not find a correlation between metal blood levels and oxidative stress indicators, the physical activity of the patients or the position of the implants between groups. CONCLUSIONS: The use of M-M bearing surfaces in THA raises the levels of metals in the blood without modifying oxidative stress regardless of the physical activity levels of the patients. Therefore, although patients with M-M bearings require close monitoring, it does not seem necessary to recommend the restriction of physical activity in patients with M-M or C-M arthroplasties.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38277495

RESUMO

BACKGROUND: Histologic grade, size, and depth are well-known prognostic factors in soft tissue sarcomas (STS). Small (< 5 cm) and superficial STS generally have an excellent prognosis when treated with appropriate surgery. However, they are often misdiagnosed and mistreated. We reported that in midterm follow-up (5 to 7 years), patients with unplanned resections of tumors with positive margins who immediately underwent a reoperation with margin-widening re-resection and postoperative radiotherapy had survival comparable to that of patients who were initially treated correctly. In that article, we included STS larger than 5 cm, deep STS, and individuals with local recurrence. However, we wanted to evaluate the impact of unplanned resection on the survival of patients who had STS with the best prognosis, small and superficial STS, with two groups that were as homogeneous as possible. QUESTION/PURPOSE: Do patients with small and superficial STS who underwent an unplanned resection have worse prognosis in the long term than those who were initially treated correctly? METHODS: We exclusively evaluated patients with small (< 5 cm) and superficial (to the deep fascia) STS. We systematically excluded deep STS. Among this subset, we identified 93 patients with superficial STS. We excluded patients with local relapse, metastatic disease, superficial STS of the head or neck, those with insufficient clinical or dosimetric information, and patients with follow-up of less than 2 years. Furthermore, our focus on investigating the most benign and homogeneous STS prompted us to exclude patients with superficial tumors greater than or equal to 5 cm. This selection was driven by the presumed better prognosis associated with smaller tumors, inevitably leading to a smaller pool of patients for direct comparison with patients who had unplanned resections. The initial expectation was to observe similar survival outcomes between cohorts. Between 1990 and 2019, a total of 17 patients underwent surgical treatment at our private, medium-size center. Of those, 29% (5 patients) were lost to follow-up before 2 years without meeting a study endpoint (relapse, metastasis or revision, reoperation, or death), leaving a total of 71% (12 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with surgery alone. During that same period, another 51 patients were referred to us after undergoing an unplanned resection of a lesion that subsequently was determined to be a soft tissue malignancy. Of those, 18% (9 patients) were lost to follow-up before 2 years without meeting a study endpoint, leaving 82% (42 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with re-excision and postoperative radiotherapy. Patients with unplanned resections had an older mean age (51± 5 versus 44 ± 7 years; p = 0.1) and a higher proportion of female patients (58% versus 38%; p = 0.07), but the groups did not differ in terms of largest diameter, histologic type, or tumor location. However, patients with planned resections had a higher proportion of high-grade STS (75% versus 55%; p = 0.07). No metastases were present in either group at diagnosis. We performed a univariate analysis of the groups. We could not perform a multivariate analysis because of the small sample. We compared the groups in terms of local recurrence and all-cause mortality using the Kaplan-Meier survivorship estimator. RESULTS: According to the Kaplan-Meier survivorship estimator, survivorship free from local recurrence at a mean of 20 years of follow-up was better in the planned resection group than in the unplanned resection group (92% [95% CI 63% to 100%] versus 69% [95% CI 54% to 81%]; p = 0.04). Furthermore, overall survivorship at 5 years was higher in the planned resection group than in the unplanned resection group (100% [95% CI 72% to 100%] versus 70% [95% CI 54% to 81%]; p = 0.04). Similarly, the planned resection group exhibited superior survivorship at 20 years of follow-up (100% [95% CI 72% to 100%] versus 62% [95% CI 47% to 75%]; p = 0.01). Metastatic disease was absent in the planned resection group, while it occurred in 12 patients in the unplanned resection group (28% [95% CI 17% to 44%]). CONCLUSION: Unplanned resection for patients with small and superficial STS was associated with a decrease in overall survival in the long term, despite the use of postoperative radiotherapy. An unplanned resection may be an important prognostic factor. Nevertheless, larger and prospective studies are needed to validate our findings. Although small and superficial lumps are usually benign, nonsarcoma surgeons should be aware that some masses may be malignant, and if in doubt, MR imaging, a biopsy before excision, or consultation with or referral to a sarcoma center should be considered before removing the mass. LEVEL OF EVIDENCE: Level III, therapeutic study.

10.
Emerg Infect Dis ; 30(1): 180-182, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063085

RESUMO

We estimated the incubation period for mpox during an outbreak in Pereira, Colombia, using data from 11 confirmed cases. Mean incubation period was 7.1 (95% CI 4.9-9.9) days, consistent with previous outbreaks. Accurately estimating the incubation period provides insights into transmission dynamics, informing public health interventions and surveillance strategies.


Assuntos
Masculino , Humanos , Colômbia/epidemiologia , Período de Incubação de Doenças Infecciosas , Surtos de Doenças , Saúde Pública , Homossexualidade Masculina
11.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1550858

RESUMO

Introducción: El cáncer bucal continúa siendo una de las neoplasias malignas en ascenso, de acuerdo con su incidencia y el importante número de muertes cada año. En este sentido, se han desarrollado programas de salud para la población que garantizan la pesquisa, la prevención y la atención de las enfermedades. Objetivo: Caracterizar a los pacientes con cáncer bucal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey durante el período 2018-2022. Métodos: Se realizó un estudio descriptivo transversal en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey en un universo de 218 pacientes, que acudieron al Servicio de Cirugía de Cabeza y Cuello del año 2018 al 2022 y tuvieron como diagnóstico cáncer bucal. La muestra se delimitó a 113 pacientes que cumplieron con los criterios de inclusión y exclusión. Resultados: El cáncer bucal predominó en el sexo masculino con 89 (78,76 %) en los años 2019 y 2021. Hubo mayor frecuencia en pacientes de piel blanca con 97 (85,84 %) y el año 2021 mostró mayor número de estos enfermos. La lengua fue la más afectada con 43 (30,05 %) pacientes, seguida por el suelo de boca en 18 (15,92 %) y las encías en 17 (15,04 %) pacientes. Según el estadio existió un predominio del IV en 61 (53,98 %) enfermos, seguido por el III con un 18,58 % de pacientes diagnosticados. Conclusiones: Prevaleció del sexo masculino en el grupo de 60 a 79 años y los pacientes de piel blanca fueron los más afectados. La localización de las lesiones se manifestó con mayor incidencia en la lengua y los estadios IV y III de la enfermedad son los más representativos en el momento del diagnóstico.


Introduction: Oral cancer continues to be one of the malignant neoplasms on the rise, according to its incidence and the significant number of deaths each year. In this sense, health programs have been developed for the population that guarantee screening, prevention and care of the diseases. Objective: To characterize patients with oral cancer at the María Curie Oncological Teaching Provincial Hospital in Camagüey province during the period 2018-2022. Methods: A cross-sectional descriptive study was carried out in the María Curie Oncological Teaching Provincial Hospital of Camagüey province in a universe of 218 patients, who attended the Head and Neck Surgery Service from 2018 to 2022 and had oral cancer as diagnosis. The sample was limited to 113 patients who met the inclusion and exclusion criteria. Results: Oral cancer predominated in the male sex with 89 (78.76%) in the years 2019 and 2021. There was a higher incidence in patients with white skin with 97 (85.84%) and the year 2021 showed a higher number of these patients. The tongue was the most affected with 43 (30.05%) patients, followed by the floor of the mouth in 18 (15.92%) and the gums in 17 (15.04%) patients. According to stage there was a predominance of stage IV in 61 (53.98%) patients, followed by stage III with 18.58% of patients diagnosed. Conclusions: Male sex prevailed in the 60 to 79 years age group and white skin patients were the most affected. The location of the lesions manifested with greater incidence on the tongue and stages IV and III of the disease are the most representative at the time of diagnosis.

12.
Front Pharmacol ; 14: 1098378, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38094892

RESUMO

Introduction: Zuotai is an ancient mineral-herbal mixture containing ß-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicine Rasasindura. However, one of the key problems faced by Zuotai is that its indications are ambiguous. Our previous study found that Zuotai exhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation. Methods: Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect of Zuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress. Results: It was observed that Zuotai and ß-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice. Zuotai and ß-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated with Zuotai; however, there was no statistically significant difference. Although Zuotai increased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; and Zuotai showed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients. Conclusion: Zuotai exhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.

13.
Am J Transplant ; 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38158189

RESUMO

The diabetic population is witnessing a rise in obesity rates, creating specific hurdles for individuals seeking pancreas transplantation because they are frequently disqualified due to their elevated body weight. Introducing a robotic-assisted approach to transplantation has been proven to yield improved outcomes, particularly in patients with obesity. A retrospective analysis was conducted between January 2015 and September 2023. The study included a total of 140 patients, with 16 receiving robotic-assisted simultaneous pancreas-kidney transplantation (RSPK) and 124 undergoing open approach simultaneous pancreas-kidney transplantation (OSPK) during the study period. The median age was 45 (36.8-52.7) and 44.5 years (36.8-51.8) (RSPK vs OSPK, P = .487). There were no significant differences in demographics except body mass index (RSPK vs OSPK, 34.9 vs 28.1, P < .001) and a higher percentage of patients with high cardiac risk in the RSPK group. The robotic approach has a lengthier overall operative time and warm ischemia time. Surgical and nonsurgical complications at 30-days and 1-year grafts and patient survival (93.8% vs 96.8%, RSPK vs OSPK, P = .521) were similar. Our findings suggest that employing robotic assistance in simultaneous pancreas-kidney transplantation is safe. Wider adoption and utilization of this technique could potentially improve transplant accessibility for individuals with obesity and diabetes.

15.
Front Public Health ; 11: 1285057, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026436

RESUMO

Sex-related drug consumption and its health-related consequences have gained relevance in the assessment of patients with sexually transmitted infections (STIs), which pose a significant challenge to public health. We aim to assess the prevalence and characteristics of drug consumption and chemsex practices, describe the associated risk factors among general individuals attending an STI clinic, and evaluate the psychological impact associated with these behaviors. We conducted an online anonymous survey offered to patients with a diagnosis of STI in a tertiary hospital in Spain. Data included sociodemographic characteristics, sexual preferences and behavior, and assessment of drug use, chemsex, and psychological and mental health symptoms. Data from 145 subjects was collected, with a higher proportion of cis-gender men (71%), and a median age of 32 years. 64 participants (44%) reported drug use in the last year, with an observed 33.8% prevalence of chemsex consumption. Drug use and chemsex were more frequent among cis-gender men, Men who have Sex with Men (MSM), people living with HIV (PLHIV), and those reporting previous group sex. Poppers and cannabis were the most frequently reported drugs, with a prevalence close to 20% for cocaine, mephedrone, extasis, and GHB. Consequences related to drug use included unpleasant physical sensations, sexual dysfunction, and impaired sexual experience after reduction or drug discontinuation. The prevalence of drug use and chemsex practices are high among patients evaluated for STIs, especially between men, MSM, and subjects practicing group sex. The study highlights the urgent need for targeted interventions on prevention and reduction of their impact on health and social well-being.


Assuntos
Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Adulto , Homossexualidade Masculina , Prevalência , Infecções Sexualmente Transmissíveis/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Fatores de Risco
16.
Sci Rep ; 13(1): 17618, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848510

RESUMO

Hip fractures represent a high burden and are associated with mortality in up to 30% of the cases. Stroke complications can be devastating and increase mortality and disability in elderly patients. This study aimed to determine the overall incidence and risk factors for stroke in patients with hip fractures. A systematic search of the literature using PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was carried out. Studies have reported the incidence of stroke in patients > 50 years of age with hip fractures. Data were extracted according to PRISMA guidelines (PROSPERO: CRD42023384742). Data were combined using Review Manager version 5.4. A random-effects model was adopted if a significant heterogeneity was observed. The primary outcome was the incidence of stroke in patients with hip fractures. The secondary outcomes of interest included the influence on the incidence of demographic factors, associated conditions, habits, and analytical parameters. Of the 635 initially retrieved studies, 18 were included, with 256,197 patients. The mean age of the patients ranged from 55 to 84 years old. The overall incidence of stroke in patients with hip fracture was 6.72% (95% CI 4.37-9.07%. The incidence of stroke by region was highest in the American continent (8.09%, 95% CI 3.60-12.58%; P > 0.001). Regarding associated conditions diabetes significantly increased the risk of stroke (OR 1.80, 95% CI 1.41-2.30). Respect to patient characteristics, BMI greater than 24.4 and female gender did not significantly increase the risk of stroke: (OR 1.07, 95% CI 0.74-1.56) and (OR 1.15, 95% CI 0.91-1.46). Lastly, lower albumin concentrations were a risk factor for stroke in patients with hip fracture (MD - 3.18, 95% CI - 4.06 to 2.31). In conclusion, the incidence of stroke after hip fracture was 6.72%. The incidence of stroke increases over time, and the closely associated risk factors are diabetes and low albumin level.


Assuntos
Diabetes Mellitus , Fraturas do Quadril , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Incidência , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Albuminas
17.
JCI Insight ; 8(23)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-37856222

RESUMO

Thyroid hormone (TH) levels are low during development, and the deiodinases control TH signaling through tissue-specific activation or inactivation of TH. Here, we studied human induced pluripotent stem cell-derived (iPSC-derived) hepatic organoids and identified a robust induction of DIO2 expression (the deiodinase that activates T4 to T3) that occurs in hepatoblasts. The surge in DIO2-T3 (the deiodinase that activates thyroxine [T4] to triiodothyronine [T3]) persists until the hepatoblasts differentiate into hepatocyte- or cholangiocyte-like cells, neither of which expresses DIO2. Preventing the induction of the DIO2-T3 signaling modified the expression of key transcription factors, decreased the number of hepatocyte-like cells by ~60%, and increased the number of cholangiocyte-like cells by ~55% without affecting the growth or the size of the mature liver organoid. Physiological levels of T3 could not fully restore the transition from hepatoblasts to mature cells. This indicates that the timed surge in DIO2-T3 signaling critically determines the fate of developing human hepatoblasts and the transcriptome of the maturing hepatocytes, with physiological and clinical implications for how the liver handles energy substrates.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Transcriptoma , Fígado/metabolismo , Hepatócitos/metabolismo , Hormônios Tireóideos/metabolismo , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Organoides/metabolismo
18.
Sci Rep ; 13(1): 16493, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37779117

RESUMO

This study aimed to compare the efficacy and safety of arthroscopy with physiotherapy or joint lavage in patients with femoroacetabular impingement (FAI). A meta-analysis using PubMed, Embase, Scopus, and the Cochrane Collaboration Library databases was performed in September 2022. We included studies focusing on patients with FAI who underwent arthroscopic surgery versus those who underwent physiotherapy or arthroscopic lavage. The outcomes were functional scores (iHOT-33 and HOS ADL) and adverse events. Randomized clinical trials were included in the study. The risk of bias in each study was assessed according to Cochrane guidelines for clinical trials. The data were combined using Review Manager version 5.4. (PROSPERO CRD42022375273). Six RCTs were included, from a pool of 839 patients (407 females). The iHOT-33 and HOS ADL scales showed significant differences at 12 months in favor of the arthroscopy group (MD, 10.65; 95% CI 6.54-4.76) and (MD, 8.09; 95% CI 3.11-13.07). MCID was not achieved through arthroscopy in functional variables. The rates of osteoarthritis (OR, 6.18; 95% CI 1.06-36.00) and numbness (OR, 73.73; 95% CI 10.00-43.92) were significantly higher in the arthroscopy group. Arthroscopic surgery showed statistical superiority over the control group without exceeding the MCID in most studies; however, the results might have been influenced by secondary variables. Finally, arthroscopic surgery results in a high rate of conversion to osteoarthritis.


Assuntos
Impacto Femoroacetabular , Feminino , Humanos , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/cirurgia , Artroscopia/efeitos adversos , Artroscopia/métodos , Resultado do Tratamento , Atividades Cotidianas , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Cartilage ; : 19476035231191202, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723972

RESUMO

OBJECTIVE: This study was conducted to assess the effect of osteochondroplasty on osteoarthritis (OA) prevention, comparing radiological evolution between identical hips from the same patient who had undergone unilateral surgery. DESIGN: We retrospectively reviewed radiological evolution between hips with similar shape from the same patient who had undergone unilateral surgery. In all, 56 FAI patients (112 hips) with a mean age of 42.18 ± 9.16 years and had undergone unilateral arthroscopy treatment have been included. Four independent researchers measured Wiberg, Acetabular and Alpha angles, Extrusion index, and Tönnis classification preoperatively to verify that operated and non-operated hips had the same shape. OA evolution was assessed by joint space width (JSW) in 3 different articular points and Tönnis classification. RESULTS: No preoperative anatomical differences were present between groups (P > 0.05). At the end of follow-up (31.9 months), a decrease of JSW in the 3 points measured was found in OP hips (OP vs. N-OP; P < 0.01). These results were correlated with changes in the proportion of patients who progressed to grade III in Tönnis classification (from 1.3% preoperative to 23.2% at the end of follow-up). CONCLUSIONS: Osteochondroplasty and labrum procedures were not associated with OA prevention. The OP hips showed a faster OA degeneration, which was not seen in the N-OP. These results will encourage hip surgeons to perform further investigations to avoid the "Pandora's Box Opening Process."

20.
Nat Commun ; 14(1): 5555, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689786

RESUMO

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS). Current therapies mainly target inflammatory processes during acute stages, but effective treatments for progressive MS are limited. In this context, astrocytes have gained increasing attention as they have the capacity to drive, but also suppress tissue-degeneration. Here we show that astrocytes upregulate the immunomodulatory checkpoint molecule PD-L1 during acute autoimmune CNS inflammation in response to aryl hydrocarbon receptor and interferon signaling. Using CRISPR-Cas9 genetic perturbation in combination with small-molecule and antibody-mediated inhibition of PD-L1 and PD-1 both in vivo and in vitro, we demonstrate that astrocytic PD-L1 and its interaction with microglial PD-1 is required for the attenuation of autoimmune CNS inflammation in acute and progressive stages in a mouse model of MS. Our findings suggest the glial PD-L1/PD-1 axis as a potential therapeutic target for both acute and progressive MS stages.


Assuntos
Microglia , Esclerose Múltipla , Animais , Camundongos , Astrócitos , Doenças Neuroinflamatórias , Receptor de Morte Celular Programada 1/genética , Antígeno B7-H1/genética , Inflamação
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