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1.
Geriatrics (Basel) ; 9(2)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38667520

RESUMO

This qualitative study aimed to understand men's social connectedness in later life in Portugal focusing on their perceptions, obstacles, strategies, and impact on well-being. The sample included 104 older Portuguese men over 65 years of age (Mage = 70.76 years). The qualitative data were the direct transcriptions of the answers given by participants to the electronic interview using thematic analysis. Findings revealed six overarching themes encompassing 18 subcategories: definitions of social connectedness (social support, community identity, mental health promotion, use of community structures), difficulties/obstacles in maintaining social connectedness (ageism, lack of initiative, physical limitations, psychological traits, resources), strategies/actions or resources to establish social connections (use of technology, use of community groups, leisure and sport activities, church/religion), negative impact of difficulties in establishing relevant social connections (mental health, physical health, relationships), positive actions from being socially connected (positive prescriptions to promote social connectedness), and concerns from being socially disconnected (health risks). These findings indicate that the lack of social connectedness creates social vulnerability in later life, and social support is needed to ensure safer aging among older men.

2.
Cureus ; 16(3): e56534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646242

RESUMO

We present a clinical case of a 79-year-old male admitted to inpatient care for longstanding asthenia and respiratory symptoms. Associated features were polyserositis, multiple enlarged lymphatic nodules, acute kidney injury, and heart failure. The patient's recent medical history revealed SARS-CoV-2 vaccination a week prior and an upper respiratory tract infection. The laboratory results from thoracentesis were compatible with a transudate, with no immunological stain. Epstein-Barr virus polymerase chain reaction (PCR) was positive. The thoracic, abdominal, and pelvic CT scans revealed multiple enlarged lymphatic nodules, worsening the pre-existent polyserositis and hepatosplenomegaly. The patient began to show signs of neurologic symptoms and deterioration of the global health status. An enlarged lymphatic nodule was excised and the pathology showed human herpesvirus 8 multicentric Castleman disease. The disease evolved rapidly into hematological dysfunction and blood transfusions were necessary. Even though the patient was started on high-dose rituximab therapy combined with etoposide, the disease evolved into multiorgan dysfunction with a fatal outcome.

3.
bioRxiv ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38562770

RESUMO

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder. Why the incidence of 22q11.2DS is much greater than that of other genomic disorders remains unknown. Short read sequencing cannot resolve the complex segmental duplicon structure to provide direct confirmation of the hypothesis that the rearrangements are caused by non-allelic homologous recombination between the low copy repeats on chromosome 22 (LCR22s). To enable haplotype-specific assembly and rearrangement mapping in LCR22 regions, we combined fiber-FISH optical mapping with whole genome (ultra-)long read sequencing or rearrangement-specific long-range PCR on 24 duos (22q11.2DS patient and parent-of-origin) comprising several different LCR22-mediated rearrangements. Unexpectedly, we demonstrate that not only different paralogous segmental duplicon but also palindromic AT-rich repeats (PATRR) are driving 22q11.2 rearrangements. In addition, we show the existence of two different inversion polymorphisms preceding rearrangement, and somatic mosaicism. The existence of different recombination sites and mechanisms in paralogues and PATRRs which are copy number expanding in the human population are a likely explanation for the high 22q11.2DS incidence.

4.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612533

RESUMO

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.


Assuntos
Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Neoplasias Colorretais/diagnóstico , Hiperplasia , Carcinogênese , Antígenos Virais de Tumores
5.
J Med Virol ; 96(3): e29511, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469884

RESUMO

To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.


Assuntos
Infecções por HIV , Varíola dos Macacos , Humanos , Contagem de Linfócito CD4 , Progressão da Doença , RNA
6.
ACS Nano ; 18(14): 10088-10103, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38535625

RESUMO

Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.


Assuntos
Nanopartículas , Neoplasias , Humanos , Lectinas/metabolismo , Glicosilação , Glicopeptídeos/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo , Imunoterapia/métodos , Células Dendríticas
7.
Int J Mol Sci ; 25(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38542435

RESUMO

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.


Assuntos
Espectrometria de Massas em Tandem , Neoplasias da Bexiga Urinária , Humanos , Glicosilação , Transportador de Glucose Tipo 1/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Bexiga Urinária/patologia
8.
J Control Release ; 367: 540-556, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301927

RESUMO

Cancer presents a high mortality rate due to ineffective treatments and tumour relapse with progression. Cancer vaccines hold tremendous potential due to their capability to eradicate tumour and prevent relapse. In this study, we present a novel glycovaccine for precise targeting and immunotherapy of aggressive solid tumours that overexpress CD44 standard isoform (CD44s) carrying immature Tn and sialyl-Tn (sTn) O-glycans. We describe an enzymatic method and an enrichment strategy to generate libraries of well-characterized cancer-specific CD44s-Tn and/or sTn glycoproteoforms, which mimic the heterogeneity found in tumours. We conjugated CD44-Tn-derived glycopeptides with carrier proteins making them more immunogenic, with further demonstration of the importance of this conjugation to overcome the glycopeptides' intrinsic toxicity. We have optimized the glycopeptide-protein maleimide-thiol conjugation chemistry to avoid undesirable cross-linking between carrier proteins and CD44s glycopeptides. The resulting glycovaccines candidates were well-tolerated in vivo, inducing both humoral and cellular immunity, including immunological memory. The generated antibodies exhibited specific reactivity against synthetic CD44s-Tn glycopeptides, CD44s-Tn glycoengineered cells, and human tumours. In summary, we present a promising prototype of a cancer glycovaccine for future therapeutical pre-clinical efficacy validation.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Vacinas Combinadas , Antígenos Glicosídicos Associados a Tumores/química , Glicoconjugados , Neoplasias/terapia , Imunoterapia , Glicopeptídeos/química , Proteínas de Transporte , Recidiva , Receptores de Hialuronatos
10.
Antiviral Res ; 222: 105795, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38181855

RESUMO

BACKGROUND & AIMS: It has been reported that specific killer-cell immunoglobulin-like receptors (KIRs) and HLA genotype combinations, such as KIR2DS4/HLA-C1 with presence of KIRDL2 or KIRDL3, homozygous KIRDL3/HLA-C1 and KIR3DL1/≥2HLA-Bw4, are strongly associated with the lack of active infection and seroconversion after exposition to hepatitis C virus (HCV). OBJECTIVE: To determine whether these KIR-HLA combinations are relevant factors involved in that phenotype. PATIENTS AND METHODS: In this retrospective case-control study, genotype data from a genome-wide association study previously performed on low susceptibility to HCV-infection carried out on 27 high-risk HCV-seronegative (HRSN) individuals and 743 chronically infected (CI) subjects were used. HLA alleles were imputed using R package HIBAG v1.2223 and KIR genotypes were imputed using the online resource KIR*IMP v1.2.0. RESULTS: It was possible to successfully impute at least one KIR-HLA genotype combination previously associated with the lack of infection and seroconversion after exposition to HCV in a total of 23 (85.2%) HRSN individuals and in 650 (87.5%) CI subjects. No KIR-HLA genotype combination analyzed was related to the HRSN condition. CONCLUSIONS: Our results suggest that those KIR-HLA genotype combinations are not relevant factors involved in the lack of infection and seroconversion after exposition to HCV. More studies will be needed to completely understand this phenotype.


Assuntos
Hepacivirus , Hepatite C , Humanos , Hepacivirus/genética , Estudos de Casos e Controles , Estudos Retrospectivos , Estudo de Associação Genômica Ampla , Soroconversão , Genótipo , Receptores KIR/genética
11.
Healthcare (Basel) ; 12(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38255117

RESUMO

This was a prospective observational study based on clinical simulation courses taught in 2017 at the IDEhA Simulation Center of Alcorcón Foundation University Hospital. Two courses in metabolic emergencies (MEs) and respiratory emergencies (REs) were offered to primary care physicians all over Spain. The main objective was to teach nontechnical skills (crisis resource management). Using a modified five-level Kirkpatrick-Phillips education evaluation model, level I (reaction, K1), level II (learning, K2) and level III (behavioral change, K3) changes were evaluated through surveys at the end of the courses and one year later. Thirty courses were held (15 ME courses and 15 RE courses) with 283 primary care physicians. The overall satisfaction (K1) was high: ME courses, 9.5/10; RE courses, 9.6/10. More than 80% of the participants rated the organization, resources, content, debriefing and scenarios as excellent, with no significant differences between the two courses. After one year (156 responses), the respondents for both courses reported that they would repeat the training annually (K2), encourage debriefing with colleagues (K3) and have modified some aspects of their workplace (K3), citing improvements in procedures and in the organization of the health team as the most important. After the ME course, few participants, i.e., 5 (6%), reported providing improved care to patients; after the RE course, 15 (19%) participants reported providing improved care; the difference between groups was significant (p < 0.05). Compared with the ME course, the RE course imparted greater knowledge about patient safety (K2) (38 (49%) vs. 24 (31%) (p < 0.05)) and more useful tools for daily clinical practice (K3) (67% vs. 56.4%) and resulted in participants paying more attention to personal performance and to colleagues when working as a team (K2) (64% vs. 50%). Clinical simulation courses are highly valued and potentially effective for training primary care physicians in patient safety and CRM tools. Future studies with objective measures of long-term impact, behavior in the workplace (K3) and benefits to patients (K4) are needed. Based on the results of our study, the areas that are important are those aimed at improving procedures and the organization of health teams.

13.
Sci Rep ; 13(1): 23061, 2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38155275

RESUMO

Suboptimal vaccine response is a significant concern in patients with Inflammatory Bowel Disease (IBD) receiving biologic drugs. This single-center observational study involved 754 patients with IBD. In Phase I (October 2020-April 2021), 754 IBD participants who had not previously received the SARS-CoV-2 vaccine, underwent blood extraction to assess the seroprevalence of SARS-CoV-2 infection and IBD-related factors. Phase II (May 2021-October 2021) included a subgroup of 52 IBD participants with confirmed previous SARS-CoV-2 infection, who were studied for humoral and cellular response to the SARS-CoV-2 vaccine. In Phase I, treatment with anti-TNF was associated with lower rates of seroconversion (aOR 0.25 95% CI [0.10-0.61]). In Phase II, a significant increase in post-vaccination IgG levels was observed regardless of biologic treatment. However, patients treated with anti-TNF exhibited significantly lower IgG levels compared to those without IBD therapy (5.32 ± 2.47 vs. 7.99 ± 2.59 U/ml, p = 0.042). Following vaccination, a lymphocyte, monocyte, and NK cell activation pattern was observed, with no significant differences between patients receiving biologic drugs and those without IBD treatment. Despite lower seroprevalence and humoral response to the SARS-CoV-2 vaccine in patients treated with anti-TNF, the cellular response to the vaccine did not differ significantly from that patients without IBD therapy.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , Vacinas contra COVID-19 , Estudos Soroepidemiológicos , Inibidores do Fator de Necrose Tumoral , SARS-CoV-2 , Doenças Inflamatórias Intestinais/tratamento farmacológico , Vacinação , Imunoglobulina G
14.
Open Forum Infect Dis ; 10(11): ofad532, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37965642

RESUMO

Background: Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. Methods: This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Results: Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], -24 to 46.3) dB/m versus -4 (IQR, -35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05-1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07-2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1-1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1-1.02]; P = .027) were associated with HS at the end of follow-up. Conclusions: The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

15.
BMC Ecol Evol ; 23(1): 64, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919666

RESUMO

BACKGROUND: The negative impacts of climate change on biodiversity are consistently increasing. Developmental stages are particularly sensitive in many ectotherms. Moreover, sex-specific differences in how organisms cope with thermal stress can produce biased sex ratios upon emergence, with potentially major impacts on population persistence. This is an issue that needs investigation, particularly testing whether thermal selection can alleviate sex ratio distortions in the long-term is a critical but neglected issue. Here, we report an experiment analyzing the sex ratio patterns at different developmental temperatures in Drosophila subobscura populations subjected to long-term experimental evolution (~ 30 generations) under a warming environment. RESULTS: We show that exposure to high developmental temperatures consistently promotes sex ratio imbalance upon emergence, with a higher number of female than male offspring. Furthermore, we found that thermal selection resulting from evolution in a warming environment did not alleviate such sex ratio distortions generated by heat stress. CONCLUSIONS: We demonstrate that heat stress during development can lead to clear sex ratio deviations upon emergence likely because of differential survival between sexes. In face of these findings, it is likely that sex ratio deviations of this sort occur in natural populations when facing environmental perturbation. The inability of many insects to avoid thermal shifts during their (more) sessile developmental stages makes this finding particularly troublesome for population subsistence in face of climate warming events.


Assuntos
Drosophila , Razão de Masculinidade , Animais , Masculino , Feminino , Temperatura , Mudança Climática , Insetos
16.
Vet Sci ; 10(11)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37999454

RESUMO

Cytospins are important for evaluating fluids with very low cellularity such as cerebrospinal fluid (CSF). The aim of this study was to compare the CSF cytospin preparations obtained from automated and manual cytocentrifugation methods. A prospective case series was performed to analyze canine CSF samples using both centrifugation methods. The cytospins were processed within 30-60 min and prepared simultaneously in a conventional automated cytocentrifuge and in an in-house manual cytocentrifuge, using a fixed volume of CSF fluid. The cellularity, differential cell count and the proportion of cell artifacts (pseudopods and vacuolization) were blindly assessed in the cytospin preparations obtained using the two methods. The agreement and correlation between both methods were analyzed. There were 55 dogs enrolled (48 prospectively and 7 retrospectively) in the study. 38 dogs had normal total nucleated cell counts, while 17 had pleocytosis. Automated and manual cytocentrifugation had similar cell yields, and no significant differences in differential cell counts or the presence of artifacts existed between both methods. In cases with pleocytosis, the cytologic diagnosis obtained using each method was similar. Manual cytocentrifugation of CSF is a reliable and economic method designed for routine clinical practice. Its use reduces the specimen deterioration related to processing and analysis delays when samples are transported to external laboratories for evaluation.

17.
AIDS ; 37(14): 2259-2262, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37877283

RESUMO

We studied hepatic steatosis in people with HIV (PWH) who switched to an integrase inhibitor (INSTI)-based regimen. One hundred and fifty-four PWH were included. After 48 weeks, median (Q1-Q3) weight gain was 1.2 (-0.6 to 3.8) kg and median (Q1-Q3) controlled attenuation parameter (CAP) change was -4 (-33 to 27) dB/m. Weight gain was weakly correlated with CAP change [R2 95% confidence interval (CI) = 0.144 (-0.014 to 0.296); P = 0.074)]. Changes in hepatic steatosis after switching to INSTI-based regimens do not seem to parallel weight gain after 1 year.


Assuntos
Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Infecções por HIV , Inibidores de Integrase de HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Aumento de Peso
18.
PLoS One ; 18(10): e0293216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37856443

RESUMO

We aimed to evaluate the effects of post-ruminal supply of urea (PRU) on nutritional status, and liver metabolism of pregnant beef cows during late gestation. Twenty-four Brahman dams, pregnant from a single sire, and weighing 545 kg ± 23 kg were confined into individual pens at 174 ± 23 d of gestation, and randomly assigned into one of two dietary treatments up to 270 d of gestation: Control (CON, n = 12), consisting of a basal diet supplemented with conventional urea, where the cows were fed with diets containing 13.5 g conventional urea per kg dry matter; and PRU (PRU, n = 12), consisting of a basal diet supplemented with a urea coated to extensively prevent ruminal degradation while being intestinally digestible, where the cows were fed with diets containing 14,8 g urea protected from ruminal degradation per kg dry matter. Post-ruminal supply of urea reduced the urine levels of 3-methylhistidine (P = 0.02). There were no differences between treatments for dry matter intake (DMI; P = 0.76), total digestible nutrient (TDN) intake (P = 0.30), and in the body composition variables, such as, subcutaneous fat thickness (SFT; P = 0.72), and rib eye area (REA; P = 0.85). In addition, there were no differences between treatments for serum levels of glucose (P = 0.87), and serum levels of glucogenic (P = 0.28), ketogenic (P = 0.72), glucogenic, and ketogenic (P = 0.45) amino acids, neither for urea in urine (P = 0.51) as well as urea serum (P = 0.30). One the other hand, enriched pathways were differentiated related to carbohydrate digestion, and absorption, glycolysis, pyruvate metabolism, oxidative phosphorylation, pentose phosphate pathway, and biosynthesis of amino acids of the exclusively expressed proteins in PRU cows. Shifting urea supply from the rumen to post-ruminal compartments decreases muscle catabolism in cows during late gestation. Our findings indicate that post-ruminal urea supplementation for beef cows at late gestation may improve the energy metabolism to support maternal demands. In addition, the post-ruminal urea release seems to be able to trigger pathways to counterbalance the oxidative stress associated to the increase liver metabolic rate.


Assuntos
Leite , Estado Nutricional , Animais , Bovinos , Feminino , Gravidez , Aminoácidos/metabolismo , Ração Animal/análise , Dieta/veterinária , Digestão , Fermentação , Lactação , Fígado/metabolismo , Leite/metabolismo , Rúmen/metabolismo , Ureia/metabolismo
19.
J Antimicrob Chemother ; 78(10): 2591-2596, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37671831

RESUMO

OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Humanos , Antivirais/farmacologia , Coinfecção/tratamento farmacológico , Coinfecção/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos como Assunto , Estudos Multicêntricos como Assunto
20.
Respir Med ; 219: 107411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37717791

RESUMO

INTRODUCTION: Chronic respiratory diseases represent a significant burden of disease globally, with high morbidity and mortality. Individuals living with these conditions, as well as their families, face considerable physical, emotional and social challenges. Palliative care might be a valuable approach to address their complex needs, but evidence to prove this is still scarce. OBJECTIVES: This systematic review aimed to study the effectiveness of palliative care interventions in health-related outcomes (quality of life, symptom control, symptom burden, psychological well-being, advance care planning, use of health services, and survival) in chronic respiratory patients. METHODS: Pubmed, Cochrane and Web of Science were searched for trials published in the last 10 years, comparing palliative care interventions to usual care, in patients with chronic respiratory diseases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. RESULTS: Eight studies were included, seven randomized controlled trials and one cluster-controlled trial; the former with moderate risk of bias and the latter with high risk of bias. Findings revealed that palliative interventions improve breathlessness control and advance care planning. There were no significant differences for the other outcomes. CONCLUSIONS: Palliative care appears to have a beneficial effect on breathlessness, one of the most distressing symptoms in patients suffering from chronic respiratory diseases and allows for advanced care planning. Additional research, with more robust trials, is needed to draw further conclusions about other health-related outcomes.


Assuntos
Planejamento Antecipado de Cuidados , Cuidados Paliativos , Humanos , Qualidade de Vida/psicologia , Dispneia , Ansiedade
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