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Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.
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Adenoma , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasia Endócrina Múltipla Tipo 1/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Adulto , Estudos Retrospectivos , Adenoma/epidemiologia , Adenoma/patologia , Pessoa de Meia-Idade , Seguimentos , Adulto Jovem , Prognóstico , Progressão da Doença , Adolescente , Resultado do Tratamento , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Prolactinoma/epidemiologiaRESUMO
BACKGROUND: The function of mucosal secretory IgA (SIgA) seems to be paramount in the immune response against SARS-CoV-2 however, there are few studies addressing this issue specifically in the institutionalized older population. This study aims to determine the levels of secretory IgA against the S1 domain of the SARS-CoV-2 spike (SIgA-S1) in older people living in nursing homes (NH) and to investigate the differences in baseline characteristics, severity of COVID-19, duration of symptoms, 30-day mortality, and reinfection according to the levels of SIgA-S1. METHODS: In this multicentre longitudinal study, conducted in two NHs attended in coordination with a hospital-based Geriatric team, 305 residents (87.3 years, 74.4% female) were included. A massive collection of nasopharyngeal samples was carried out after the first wave of COVID-19 in May 2020 and an ELISA analysis of SIgA-S1 was performed on frozen samples in May 2023. Values of SIgA-S1 ≥ 57.6 U/mL ("cut-off point") were considered "induced". Resident medical records were reviewed to assess symptoms, comprehensive geriatric assessment (CGA), reinfection, and overall 30-day mortality. RESULTS: At the time of sample collection, 274 residents (89.8%) exhibited "induced" SIgA-S1 levels (≥ 57.6 U/mL), 46 (15.1%) tested positive for PCR SARS-CoV-2, and 170 (57%) had experienced COVID-19 symptoms. "Induced" SIgA-S1 patients were more likely to be symptomatic (60.3% vs. 29%; p < 0.001) and exhibited upper respiratory tract symptoms more frequently (25.1% vs. 6.5%; p = 0.020) compared to "non-induced" patients. Patients with severe disease and duration of symptoms > 10 days had higher levels of SIgA-S1 than those with mild disease (252 vs.192.6 U/mL; p = 0.012) or duration ≤ 10 days (270.5 vs. 208.1 U/mL; p = 0.043), respectively. No significant differences were observed in age, sex, CGA, duration of symptoms, disease severity, overall 30-day-mortality, or reinfection between "induced" and "non-induced" residents. CONCLUSIONS: Levels of SIgA-S1 are associated with the duration and type of COVID-19 symptoms, along with the severity of infection. While these findings shed light on the knowledge of SIgA-S1, further interdisciplinary studies are warranted to better understand the immune response to SARS-CoV-2 infection.
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COVID-19 , Imunoglobulina A Secretora , Casas de Saúde , Humanos , COVID-19/epidemiologia , Feminino , Masculino , Casas de Saúde/tendências , Idoso de 80 Anos ou mais , Estudos Longitudinais , Idoso , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
Introduction: The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors. Methods: Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses. Results: Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody. Conclusions: In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D.
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Autoanticorpos , Diabetes Mellitus Tipo 1 , Progressão da Doença , Humanos , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Masculino , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Criança , Adolescente , Família , Autoimunidade , Adulto Jovem , Pré-Escolar , Seguimentos , Predisposição Genética para DoençaRESUMO
Surgical intervention is a key element in the management of patients diagnosed with mucormycosis. A retrospective cohort study was carried out, in which patients with a proven diagnosis of mucormycosis were evaluated over a period of 10 years, according to the MSGERC criteria. A descriptive analysis of the clinical characteristics, comorbidities, imaging, and microbiology studies, as well as medical and surgical treatment and the type of prosthesis was carried out. A total of 22 cases were identified, of which 54.5% (n = 12) of the population were men. Furthermore, 77.2% (n = 17) of the population had diabetes mellitus. The main antifungal treatment implemented was liposomal amphotericin B (77.2%, n = 17). The most affected structures in our patients were the paranasal sinuses (n = 18; 81%), followed by the maxilla and orbit (n = 15; 68%), nose (n = 12; 54%), central nervous system (n = 11; 50%), and skin and soft tissues (n = 2; <1%). Of the total population, 59.09% (n = 13) of patients underwent maxillofacial surgery, of which 61.53% (n = 8) required some type of prosthetic rehabilitation. Orbital exenteration and maxillectomy were the most frequent surgeries, accounting for 69.23% (n = 9), while skull base drainage was performed in four patients (30.76%). Of the total number of patients (n = 22), eight died (36.36%). Appropriate surgical management according to the affected structures, considering not only increasing the patient's survival, but also considering the aesthetic and functional consequences, will require subsequent rehabilitation.
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The knowledge of the polymeric composition of microplastics (MPs) is interesting because offers useful information on the resistance, durability, and degradability of these materials, also allowing progress in the control of this contamination. However, there is currently a lack of reliable standardized methods for the identification, and characterization of the plastic microparticles. This work uses different techniques in a complementary manner for the identification, and characterization of MPs that more frequently are found in the environment. A total of 10 types of plastics were collected (polystyrene (PS), polyethylene terephthalate (PETE), polyethylene (PE), high- and low-density polyethylene (HDPE and LDPE, respectively), polyvinyl chloride (PVC), polypropylene (PP), polytetrafluoroethylene (PTFE), Polyamide (PA, Nylon 6,6) and poly-carbonate (PC)) and their chemical identification were analyzed by reflectance-attenuated infrared (FTIR-ATR). Furthermore, the samples were observed using light microscopy, and scan-ning electron microscopy (SEM). Also, staining with 12 different dyes was performed to improve the identification of microplastics. The results of this study revealed that PETE, PE, HDPE and LDPE, whose SEM images exhibited smoothness and flat uniformity of their surface, were not (or less) susceptible to adsorb staining solutions while PP, PA, PVC, and PTFE, were capable of adsorbing the dye solutions.
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This study evaluates the antiallodynic and antihyperalgesic effects of LMH-2, a new haloperidol (HAL) analog that acts as sigma-1 receptor (σ1â¯R) antagonist, in diabetic mice using a model of neuropathic pain induced by chronic hyperglycemia. Additionally, we compared its effects with those of HAL. Hyperglycemia was induced in mice by nicotinamide-streptozotocin administration (NA-STZ, 50-130â¯mg/kg). Four weeks later, mechanical allodynia was assessed using the up-down method, and hyperalgesia was evoked with formalin 0.5%. We evaluated antiallodynic and antihyperalgesic effects of LMH-2 (5.6-56.2â¯mg/kg), HAL (0.018-0.18â¯mg/kg) and gabapentin (GBP, 5.6-56.2â¯mg/kg). The results showed that LMH-2 had a more significant antiallodynic effect compared to HAL and GBP (90.4±8.7 vs 75.1±3.1 and 41.9±2.3%, respectively; P<0.05), as well as an antihyperalgesic effect (96.3±1.2 vs 86.9±7.41 and 86.9±4.8%, respectively; P<0.05). Moreover, the antiallodynic and antihyperalgesic effect of both LMH-2 and HAL were completely abolished by PRE-084 (σ1â¯R agonist); and partially by pramipexole (a D2-like receptor agonist). Finally, the effect of all treatments on the rotarod test, barra, open field and exploratory behaviors showed that LMH-2 did not alter the animals' balance or the exploratory behavior, unlike as HAL or GBP. The molecular docking included indicate that LMH-2 has lower affinity to the D2R than HAL. These results provide evidence that LMH-2 exerts its antinociceptive effects as a σ1â¯R antagonist without the adverse effects induced by HAL or GBP. Consequently, LMH-2 can be considered a good and safe strategy for treating neuropathic pain caused by hyperglycemia in patients with diabetes.
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Analgésicos , Diabetes Mellitus Experimental , Haloperidol , Hiperalgesia , Neuralgia , Receptores sigma , Receptor Sigma-1 , Animais , Receptores sigma/antagonistas & inibidores , Receptores sigma/metabolismo , Haloperidol/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Masculino , Camundongos , Analgésicos/farmacologia , Neuralgia/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Simulação de Acoplamento Molecular , Estreptozocina , Relação Dose-Resposta a Droga , Gabapentina/farmacologiaRESUMO
Introduction: The disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they are expressed are nonspecific or present only as a laboratory finding, usually hypercalcemia. Because many of these disorders have a genetic etiology, in the present study, we sequenced a selection of 55 genes encoding the principal proteins involved in the regulation of calcium metabolism. Methods: A cohort of 79 patients with hypercalcemia were analyzed by next-generation sequencing. Results: The 30% of our cohort presented one pathogenic or likely pathogenic variant in genes associated with hypercalcemia. We confirmed the clinical diagnosis of 17 patients with hypocalciuric hypercalcemia (pathogenic or likely pathogenic variants in the CASR and AP2S1 genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the CASR gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the CYP24A1 gene). However, we also found variants in genes associated with primary hyperparathyroidism (GCM2), renal hypophosphatemia with or without rickets (SLC34A1, SLC34A3, SLC9A3R1, VDR, and CYP27B1), DiGeorge syndrome (TBX1 and NEBL), and hypophosphatasia (ALPL). Our genetic study revealed 11 novel variants. Conclusions: Our study demonstrates the importance of genetic analysis through massive sequencing to obtain a clinical diagnosis of certainty. The identification of patients with a genetic cause is important for the appropriate treatment and identification of family members at risk of the disease.
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Hipercalcemia , Hiperparatireoidismo , Recém-Nascido , Humanos , Hipercalcemia/genética , Hipercalcemia/diagnóstico , Cálcio , Perfil Genético , Mutação , Hiperparatireoidismo/genéticaRESUMO
Monogenic diabetes caused by changes in the gene that encodes insulin (INS) is a very rare form of monogenic diabetes (<1%). The aim of this work is to describe the clinical and glycaemic control characteristics over time from four members of a family diagnosed with monogenic diabetes with the novel mutation: c.206del,p.(Gly69Aalfs*62) located in exon 3 of the gene INS. 75% are females, with debut in adolescence and negative autoimmunity. In all cases, C-peptide is detectable decades after diagnosis (>0.6ng/ml). Currently, patients are being treated either with insulin in a bolus-basal regimen, oral antidiabetics or hybrid closed loop system. Monogenic diabetes due to mutation in the INS is an entity with heterogeneous presentation, whose diagnosis requires high suspicion and presents an important clinical impact. Given the lack of standards in this regard, therapy must be individualized, although insulin therapy could help preserve beta cell functionality in these subjects.
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Diabetes Mellitus , Adolescente , Feminino , Humanos , Masculino , Autoimunidade , Diabetes Mellitus/diagnóstico , Hipoglicemiantes/uso terapêutico , Insulina/genética , MutaçãoRESUMO
In this research, a molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization using oxazepam (OZ) as a template molecule and was subsequently applied as a selective sorbent for the extraction of diazepam (DZP) and its metabolites in urine samples using an SPE cartridge. OZ, temazepam (TZ), nordiazepam (NZ) and DZP were analyzed in the final extracts by high-performance liquid chromatography with diode array detection (HPLC-DAD). The SPE extraction steps were optimized, and the evaluation of an imprinting factor was carried out. The selectivity of the method for OZ versus structurally related benzodiazepines (BZDs), such as bromazepam (BRZ), tetrazepam (TTZ) and halazepam (HZ), was investigated. Under the optimum conditions, the proposed methodology provided good linearity in the range of 10-1500 ng/mL, with limit of detection values between 13.5 and 21.1 ng/mL and recovery levels for DZP and its metabolites from 89.0 to 93.9% (RSD ≤ 8%) at a concentration level of 1000 ng/mL. The proposed method exhibited good selectivity, precision and accuracy and was applied to the analysis of urine samples from a real case of DZP intake.
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The information and subsequent expression of will, so-called informed consent, have become the essential element of health right, understood as the right to autonomous choice in health, based on the fiduciary relationship between physician and patient. This gradually leads European Countries to adopt special legislations and to issue frequent judgments on the subject. However, new challenges in daily clinical practice call for further study of legal solutions. The authors analyse and compare the regulations on informed consent in health care of Italy, France, the United Kingdom, the Nordic Countries, Germany, and Spain. The health and legal contexts, existence of special regulations on informed consent and their characteristics are discussed. Informed consent resulted a mandatory requirement. Clear communication about treatment, therapeutic alternatives, and major risks, discussed in conversation, but preferably documented in writing, are agreed upon. The possibility of dissent and withdrawal of consent are also included. There is a growing interest in involving and regulating the entire health team in information and consent. Lowering the age of consent for minors or analysing the maturity of minors are attempts to increase their participation in health decisions. On another side, the protection of adult incapables persons requires greater involvement of family and fiduciaries to better adapt to changing health needs. Health policy must take responsibility for training health professionals and citizens about the value of health information and communication as a shared choice in care planning, to strengthen the bond of trust with the healthcare system and users.
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Consentimento Livre e Esclarecido , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Europa (Continente) , Atenção à Saúde/legislação & jurisprudênciaRESUMO
Nε-lysine acetylation is a common posttranslational modification observed in Escherichia coli. In the present study, integrative analysis of the proteome and acetylome was performed using label-free quantitative mass spectrometry to analyze the relative influence of three factors affecting growth. The results revealed differences in the proteome, mainly owing to the type of culture medium used (defined or complex). In the acetylome, 7482 unique acetylation sites were identified. Acetylation is directly related to the abundance of proteins, and the level of acetylation in each type of culture is associated with extracellular acetate concentration. Furthermore, most acetylated lysines in the exponential phase remained in the stationary phase without dynamic turnover. Interestingly, unique acetylation sites were detected in proteins whose presence or abundance was linked to the type of culture medium. Finally, the biological function of the acetylation changes was demonstrated for three central metabolic proteins (GapA, Mdh, and AceA).
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BACKGROUND: Since 2011, over 30 tropical Atlantic nations have experienced substantial landings of holopelagic Sargassum spp. Its decomposition results in the production of hydrogen sulfide (H2S), which, in elevated concentrations, can pose a threat to human health. This study aims to enhance our understanding of the temporal and spatial variability in H2S emissions during the decomposition of Sargassum on beaches. The primary objective is to assess potential exposure risks for local populations, tourists, and cleanup workers. METHODS: H2S levels were monitored using a SENKO sensor (SGTP-H2S; limit of detection 0.1-100 ppm; resolution 0.1 ppm) at four distances from Sargassum accumulation points of (0, 10, 30, and 40 m) in Puerto Morelos, Mexico, during 2022 and 2023. RESULTS: Elevated concentrations of H2S were detected beneath the Sargassum piles, with 23.5% of readings exceeding 5 ppm and occasional spikes above 100 ppm. Above the piles, 87.3% of the measurements remained below 2 ppm, and the remainder fell between 2.1 and 5.2 ppm. At 10 m from the shoreline, 90% of measurements registered below 0.1 ppm, and the remaining 10% were below 2 ppm. Readings at 30 and 40 m consistently recorded levels below 0.1 ppm. H2S concentrations positively correlated with Sargassum pile height, the temperature beneath the piles, and wind speed. CONCLUSIONS: Our findings suggest no immediate and significant exposure risk for residents or tourists. However, Sargassum cleanup workers face a higher exposure risk, potentially encountering concentrations above 5 ppm for nearly one-fourth of the working time.
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Sulfeto de Hidrogênio , Sargassum , Humanos , Vento , Temperatura , MéxicoRESUMO
Introducción: el tratamiento nutricional está afectado por la conducta de los sujetos para generar adherencia. Objetivo: determinar factores que influyen en la no adherencia al tratamiento nutricional en pacientes hipertensos que acuden al Hospital Regional de Coronel Oviedo, 2021. Metodología: estudio descriptivo transversal. La población estuvo comprendida por pacientes registrados en el Programa de hipertensión arterial/Departamento cardiovascular del Hospital Regional de Coronel Oviedo. Se estudiaron los datos sociodemográficos, los factores de tratamiento nutricional y el grado de adherencia al tratamiento nutricional. Resultados: participaron del estudio 206 sujetos, el 53,4 % poseía 55 años o menos y el 81,1 % fue del sexo femenino. Se pudo hallar que solo el 3,8 % de los pacientes se adhieren al tratamiento. La no adherencia al factor conocimiento estuvo relacionado con el bajo nivel educativo (p=0,032), al factor equipo de salud con provenir del área rural y tener un bajo nivel educativo (p=0,006, p=0,002), al factor paciente con provenir del área rural (p=0.002), ser de bajo nivel educativo (p=0,008) y poseer obesidad grado II y III (p=0,036). La no adherencia global estuvo relacionada a estar casado (p=0.001) y realizar trabajos domésticos (p=0,009). Conclusiones: la adherencia al tratamiento es baja en la población de estudio.
Introduction: nutritional treatment is affected by the behavior of the subjects to generate adherence. This study was carried out to determine factors that influence non-adherence to nutritional treatment in hypertensive patients who attend the Coronel Oviedo Regional Hospital, 2021. Methodology: this was a cross-sectional descriptive observational study. The population was comprised of patients registered in the hypertension department of the Coronel Oviedo Regional Hospital. Sociodemographic data, nutritional treatment factors and the degree of adherence to nutritional treatment were studied. Results: 206 subjects participated in the study, 53.4 % were 55 years old or younger and 81.1 % were female. We found that only 3.8 % of patients adhere to treatment. Non-adherence due to the knowledge factor was related to low educational level (p=0.032), to the health team factor with coming from a rural area and having a low educational level (p=0.006, p=0.002), to the patient factor with coming from a rural area (p=0.002), to have a low educational level (p=0.008) and to have obesity grade II and III (p=0.036). Global non-adherence was related to being married (p=0.001) and doing housework (p=0.009). Conclusions: adherence to treatment is low in the study population.
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BACKGROUND: With more than 7500 cases reported since April 2022, Spain has experienced the highest incidence of mpox in Europe. From 12 July onward, the modified vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for those receiving pre-exposure prophylaxis for human immunodeficiency virus (HIV-PrEP). Our aim was to assess the effectiveness of 1 dose of MVA-BN vaccine as pre-exposure prophylaxis against mpox virus (MPXV) infection in persons on HIV-PrEP. METHODS: National retrospective cohort study between 12 July and 12 December 2022. Individuals aged ≥18 years receiving HIV-PrEP as of 12 July with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of vaccine and unvaccinated controls of the same age and region. We used a Kaplan-Meier estimator, calculated risk ratios (RR) and vaccine effectiveness (VE = [1 - RR]x100). RESULTS: We included 5660 matched pairs, with a median follow-up of 62 days (interquartile range, 24-97). Mpox cumulative incidence was 5.6 per 1000 (25 cases) in unvaccinated and 3.5 per 1000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE, -38.3; 95% confidence interval [CI], -332.7 to 46.4), but VE was 65% at ≥7 days (95% CI, 22.9 to 88.0) and 79% at ≥14 days (95% CI, 33.3 to 100.0) post-vaccination. CONCLUSIONS: One dose of MVA-BN vaccine offered protection against mpox in most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.
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Infecções por HIV , Mpox , Vacinas , Vacínia , Humanos , Adolescente , Adulto , Vacínia/prevenção & controle , Estudos de Coortes , Estudos Retrospectivos , Vaccinia virus , Vacinação , Monkeypox virus , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controleRESUMO
Clavulanic acid (CLAV) is a non-antibiotic ß-lactam that has been used since the late 1970s as a ß-lactamase inhibitor in combination with amoxicillin, another ß-lactam with antibiotic activity. Its long-observed adverse reaction profile allows it to say that CLAV is a well-tolerated drug with mainly mild adverse reactions. Interestingly, in 2005, it was discovered that ß-lactams enhance the astrocytic expression of GLT-1, a glutamate transporter essential for maintaining synaptic glutamate homeostasis involved in several pathologies of the central nervous system (CNS). This finding, along with a favorable pharmacokinetic profile, prompted the appearance of several studies that intended to evaluate the effect of CLAV in preclinical disease models. Studies have revealed that CLAV can increase GLT-1 expression in the nucleus accumbens (NAcc), medial prefrontal cortex (PFC), and spinal cord of rodents, to affect glutamate and dopaminergic neurotransmission, and exert an anti-inflammatory effect by modulating the levels of the cytokines TNF-α and interleukin 10 (IL-10). CLAV has been tested with positive results in preclinical models of epilepsy, addiction, stroke, neuropathic and inflammatory pain, dementia, Parkinson's disease, and sexual and anxiety behavior. These properties make CLAV a potential therapeutic drug if repurposed. Therefore, this review aims to gather information on CLAV's effect on preclinical neurological disease models and to give some perspectives on its potential therapeutic use in some diseases of the CNS.
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Antibacterianos , beta-Lactamas , Ácido Clavulânico/uso terapêutico , Ácido Clavulânico/metabolismo , Ácido Clavulânico/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamas/metabolismo , beta-Lactamas/farmacologia , Núcleo Accumbens/metabolismo , Glutamatos/metabolismo , Glutamatos/farmacologia , Transportador 2 de Aminoácido Excitatório/metabolismoRESUMO
Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of allm/zsignals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.
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Gelo-Seco , Polietilenotereftalatos , Humanos , Testes Respiratórios/métodos , Expiração , AldeídosRESUMO
Natural products are recognized as potential analgesics since many of them are part of modern medicine to relieve pain without serious adverse effects. The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of an aqueous extract of Brassica oleracea var. italica sprouts (AEBS) and one of its main reported bioactive metabolites sulforaphane (SFN). Antinociceptive activity of the AEBS (30, 100, and 300 mg/kg, i.p. or 1000 and 2000 mg/kg, p.o.) and SFN (0.1 mg/kg, i.p.) was evaluated in the plantar test in rats to reinforce its analgesic-like activity at central level using the reference drug tramadol (TR, 50 mg/kg, i.p.). The anti-inflammatory-like response was determined in the carrageenan-induced oedema at the same dosages for comparison with ketorolac (KET, 20 mg/kg, i.p.) or indomethacin (INDO, 20 mg/kg, p.o.). A histological analysis of the swollen paw was included to complement the anti-inflammatory response. Additionally, acute toxicity observed in clinical analgesics as the most common adverse effects, such as sedation and/or gastric damage, was also explored. As a result, central and peripheral action of the AEBS was confirmed using enteral and parenteral administration, in which significant reduction of the nociceptive and inflammatory responses resembled the effects of TR, KET, or INDO, respectively, involving the presence of SFN. No adverse or toxic effects were observed in the presence of the AEBS or SFN. In conclusion, this study supports that Brassica oleracea var. italica sprouts are a potential source of antinociceptive natural products such as SFN for therapy of pain alone and associated to an inflammation condition.
Assuntos
Analgésicos , Brassica , Ratos , Animais , Dor/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Extratos VegetaisRESUMO
Remaining resilient under disruption, while also being sustainable, is essential for continued and equitable seafood supply in a changing world. However, despite the wide application of resilience thinking to sustainability research and the multiple dimensions of social-ecological sustainability, it can be difficult to ascertain how to make a supply chain both resilient and sustainable. In this review, we draw upon the socio-ecological resilience and sustainability literature to identify links and highlight concepts for managing and monitoring adaptive and equitable seafood supply chains. We then review documented responses of seafood supply networks to disruption and detail a case study to describe the attributes of a resilient seafood supply system. Finally, we outline the implications of these responses for social (including wellbeing and equity), economic and environmental sustainability. Disruptions to supply chains were categorised based on their frequency of occurrence (episodic, chronic, cumulative) and underlying themes were derived from supply chain responses for each type of disruption. We found that seafood supply chains were resilient when they were diverse (in either products, markets, consumers or processing), connected, supported by governments at all scales, and where supply chain actors were able to learn and collaborate through trust-based relationships. With planning, infrastructure and systematic mapping, these attributes also can help to build socio-ecological sustainability and move towards more adaptive and equitable seafood supply.