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1.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39062884

RESUMO

Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up.


Assuntos
Doença de Alzheimer , RNA Longo não Codificante , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Humanos , RNA Longo não Codificante/genética , Feminino , Masculino , Idoso , Medicina de Precisão/métodos , Biomarcadores , Aprendizado de Máquina , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos
2.
Diabetes Obes Metab ; 25(6): 1607-1613, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36751978

RESUMO

AIM: The Diabeloop Generation 1 (DBLG1) system is an interoperable hybrid closed-loop solution that was commercialized in Germany in March 2021. We report the longitudinal glycaemic outcomes among the first 3706 users in a real-world setting. METHODS: We performed a retrospective data collection of all consenting adult patients with type 1 diabetes who were equipped in Germany with the DBLG1 system before 30 April 2022, and with a minimum 14 days of closed-loop usage. RESULTS: In total, 3706 users (41% women, age 45.1 ± 14.5 years) met the inclusion criteria, reaching a mean follow-up of 131.0 ± 85.1 days, an overall 485 600 days of continuous glucose monitoring data, and a median time spent in closed-loop of 95.0% (IQR 89.1-97.4). The median percentage time in range (70-180 mg/dl) was 72.1% (IQR 65.0-78.9); the time below 70 mg/dl was 0.9% (0.5-1.7), the time below 54 mg/dl was 0.1% (0.1-0.3), and the median Glucose Management Index was 7.0% (6.8-7.3). Exploratory analysis of a subset of 2460 patients in whom baseline glycated haemoglobin (HbA1c) was available [7.4% (IQR 6.9-8.0)] showed that the achieved mean time in range was influenced by baseline HbA1c, ranging from 65.8 ± 9.9% (A1c ≥8.5%) to 81.3 ± 6.8% (A1c <6.5%). CONCLUSION: This large real-world analysis confirms the relevance of the DBLG1 automated insulin delivery solution for the achievement of standards of care in adult patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas , Glicemia , Automonitorização da Glicemia , Estudos Retrospectivos , Sistemas de Infusão de Insulina , Insulina/uso terapêutico , Glucose/uso terapêutico , Alemanha/epidemiologia
3.
Theor Appl Genet ; 135(1): 17-33, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34218290

RESUMO

Climate change is expected to increasingly affect rice production through rising temperatures and decreasing water availability. Unlike other crops, rice is a main contributor to greenhouse gas emissions due to methane emissions from flooded paddy fields. Climate change can therefore be addressed in two ways in rice: through making the crop more climate resilient and through changes in management practices that reduce methane emissions and thereby slow global warming. In this review, we focus on two water saving technologies that reduce the periods lowland rice will be grown under fully flooded conditions, thereby improving water use efficiency and reducing methane emissions. Rice breeding over the past decades has mostly focused on developing high-yielding varieties adapted to continuously flooded conditions where seedlings were raised in a nursery and transplanted into a puddled flooded soil. Shifting cultivation to direct-seeded rice or to introducing non-flooded periods as in alternate wetting and drying gives rise to new challenges which need to be addressed in rice breeding. New adaptive traits such as rapid uniform germination even under anaerobic conditions, seedling vigor, weed competitiveness, root plasticity, and moderate drought tolerance need to be bred into the current elite germplasm and to what extent this is being addressed through trait discovery, marker-assisted selection and population improvement are reviewed.


Assuntos
Adaptação Fisiológica , Mudança Climática , Oryza/fisiologia , Melhoramento Vegetal , Água/metabolismo , Oryza/genética , Oryza/metabolismo , Temperatura
4.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638716

RESUMO

Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several "omics", and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Técnicas de Diagnóstico Molecular , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Sequenciamento Completo do Genoma , Humanos
5.
Prev Med ; 138: 106177, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32592795

RESUMO

Suicide rates in Mexico have increased and have more than doubled in the state of Aguascalientes over the past 10 years. Few studies have been able to control for family, neighborhood, and occupational environment factors that may confound the association between psychosocial characteristics and suicidal behavior. We study suicidal behavior among adolescents and young adults in Mexico utilizing epidemiologic research strategies to overcome prior research deficiencies. In a case-control study with youth and adults 14-42 years of age, recent cases of severe suicidal behavior (n = 150) were individually matched with up to three controls who had never had a suicidal attempt by age and sex, as well as within familial, neighborhood, and occupational contexts (n = 353). Data were collected through standardized face-to-face interviews to measure suicidal behavior and several covariates, including family relations, psychological resources, hopelessness, depression, self-esteem, stress, impulsivity, anxiety, and substance use. All measures demonstrated good to excellent precision and accuracy. Compared with their matched controls, cases perceived life events as more stressful and had worse depression and familial relationships; poorer development of affective, religious, and social resources; higher levels of hopelessness and impulsive behavior; and lower self-esteem. Evidence from multivariate analysis suggests highly probable MDE combined with low self-esteem and the use of two or more drugs in the past month more clearly differentiate cases and controls and, therefore, may best predict suicidal attempt among adolescents and young adults in Aguascalientes, Mexico.


Assuntos
Ideação Suicida , Tentativa de Suicídio , Adolescente , Ansiedade , Estudos de Casos e Controles , Humanos , México , Fatores de Risco , Adulto Jovem
6.
Toxicol Appl Pharmacol ; 380: 114694, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31356930

RESUMO

Lead (Pb) exposure at high concentrations is associated with poor sperm quality, acrosome alterations, and low fertilization rate. Sperm capacitation and the acrosome reaction (AR) are required for successful fertilization. Actin polymerization is crucial for correct capacitation, and small GTPases, such as RhoA, Rac1, and Cdc42, are involved. This study aimed to evaluate the effects of Pb on sperm fertilization ability, capacitation, AR, and the mechanisms involved in mice exposed to low Pb concentrations. CD1 mice were exposed to 0.01% Pb2+ for 45 days through their drinking water and their spermatozoa were collected from the cauda epididymis-vas deferens to evaluate the following: AR (oAR: initial, sAR: spontaneous, and iAR: induced) using the PNA-FITC assay, sperm capacitation (P-Tyr levels), actin polymerization (phalloidin-TRITC), MDA production (stress oxidative marker), the RhoA, Rac1, and Cdc42 protein levels, and the in vitro fertilization (IVF). After the treatment, the blood Pb (PbB) concentration was 9.4 ±â€¯1.6 µg/dL. Abnormal sperm morphology and the oAR increased (8 and 19%, respectively), whereas the iAR decreased (15%) after a calcium ionophore challenge, and the actin polymerization decreased in the sperm heads (59%) and tails (42%). Rac1 was the only Rho protein to significantly decrease (33%). Spermatozoa from the Pb-treated mice showed a significant reduction in the fertilization rate (19%). Our data suggest that Pb exposure at environmental concentrations (PbB < 10 µg/dL) decreases the acrosome function and affects the sperm fertilization ability; this is probably a consequence of the low Rac1 levels, which did not allow adequate actin polymerization to occur.


Assuntos
Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Capacitação Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Actinas/metabolismo , Animais , Feminino , Masculino , Camundongos Endogâmicos ICR , Neuropeptídeos/metabolismo , Espermatozoides/anormalidades , Espermatozoides/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo
8.
Environ Toxicol ; 32(6): 1754-1764, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28233943

RESUMO

The indiscriminate use of pesticides in agriculture and public health campaigns has been associated with an increase of oxidative stress and DNA damage, resulting in health outcomes. Some defense mechanisms against free radical-induced oxidative damage include the antioxidant enzyme systems. The aim of this study was to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and the relationship of antioxidant enzyme levels with DNA damage among sprayers (workers) occupationally exposed to pesticides. The determinations of MDA and antioxidant enzymes were performed spectrophotometrically. The genotoxic effects were evaluated using the comet assay. The results showed a marginally significant decrease in SOD and CAT activities in the high exposure group compared to the control group. For MDA, statistically significant differences were found among people working long term vs. those working temporarily (P = 0.02) as sprayers. In the moderate exposure group, a positive correlation was observed between MDA levels and GPx activity. In the high exposure group, a negative correlation was observed between GR and CAT activities, and between MDA levels and GPx activities. Furthermore, in the high exposure group, a positive correlation between DNA damage parameters and MDA levels was observed. The results suggest an important role of antioxidant enzymes for the protection of DNA damage caused by occupational exposure to pesticides.


Assuntos
Dano ao DNA , Exposição Ocupacional/efeitos adversos , Organofosfatos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Piretrinas/toxicidade , Antioxidantes/metabolismo , Catalase/sangue , Ensaio Cometa , Estudos Transversais , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Humanos , Malondialdeído/sangue , Exposição Ocupacional/análise , Superóxido Dismutase/sangue
9.
Environ Toxicol ; 29(8): 942-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23125138

RESUMO

Methamidophos (MET), widely used in developing countries, is a highly neurotoxic organophosphate pesticide that has been associated with male reproductive alterations. Commercial formulations of pesticides used by agricultural workers and urban sprayers are responsible for thousands of intoxications in developing countries and may not have the same effects as active pure ingredients. Therefore, we compared effects of MET technical (METt) and commercial (METc) grades on sperm quality and DNA integrity. Male mice were injected (intraperitoneal, i.p.) with METt or METc (3.75, 5, and 7 mg/kg bw/day/4 days) and sacrificed 24 h post-treatment. Sperm cells collected from epididymis-vas deferens were evaluated for quality parameters, DNA damage by the comet assay, and lipoperoxidation by malondialdehyde (MDA) production. Erythrocyte acetylcholinesterase (AChE) activity was evaluated by acetylthiocholine inhibition as an index of overall toxicity. A dose-dependent AChE inhibition was observed with both formulations. Sperm quality was decreased after treatment with both MET compounds, but the commercial formulation showed stronger effects; a similar profile was observed with the DNA damage, being METc more genotoxic. None MET formulation increased MDA, suggesting no peroxidative damage involved. In summary, the commercial formulation of MET was more reprotoxic and genotoxic than the active pure ingredient, highlighting that commercial formulations must be considered for more appropriate risk assessment of pesticide exposures.


Assuntos
Dano ao DNA , Compostos Organotiofosforados/toxicidade , Praguicidas/toxicidade , Acetilcolinesterase/sangue , Animais , Ensaio Cometa , DNA/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/enzimologia , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Reprodução/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos
10.
Am J Orthopsychiatry ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546563

RESUMO

When undocumented immigrant parents are deported from the United States, they must decide whether or not to take their U.S.-born and undocumented immigrant children with them, often to countries the children have never visited or know little about. Other parents do not wait to be deported by the government and decide to relocate to their home countries with or without their children. Both sets of families experience relocation but under different circumstances. These differences deserve exploration to understand the psychological and emotional effects on children's well-being. In this cross-sectional study, we explored differences in self-concept, internalizing and externalizing behaviors, as well as the perception of the home, school, and neighborhood contexts of 178 U.S. citizen children (USCC) whose parents returned to Mexico forcibly and voluntarily. Through snowball sampling, we recruited the sample from two bordering Mexican states, Michoacán and the State of Mexico. Significant estimated marginal mean differences in internalizing and externalizing behavior problems, unhappiness, as well as parent-child conflict and support were found between USCC who relocated due to a parental deportation and those USCC whose parents relocated to Mexico voluntarily. Implications for clinicians in Mexico and the United States include recognizing the reasons, timing, decisions, events, and contexts of relocation. Findings can help inform immigration policies, practices, and future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

11.
Front Plant Sci ; 14: 1261101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023850

RESUMO

The rising cost of transplanting rice has made direct seeding an affordable alternative for rice establishment, particularly in Africa. However, direct seeding, while cost-effective, faces crop establishment challenges due to flooding. Uncontrolled water, driven by erratic rains in low-lying areas or uneven fields, limit germination. Rice possesses the unique ability of anaerobic germination, enabling it to sprout and emerge in oxygen-deprived conditions. Understanding rice's response to anaerobic stress during germination is crucial for resilience breeding. Africa, although relying on direct seeding, has made limited progress in addressing flooding during germination compared to Asia. Anaerobic stress tolerance ensures successful crop emergence even in oxygen-limited environments and can help suppress weeds, a significant challenge in direct-seeded rice cultivation. This study aims to contribute by screening for potential rice donors exhibiting anaerobic stress tolerance. We screened 200 rice genotypes at Sokoine University of Agriculture (SUA) in Morogoro, Tanzania, primarily focusing on landraces with untapped potential. Using an alpha lattice design, we conducted two anaerobic experiments in September and October 2022, adding 7 cm of standing water immediately after dry seeding for flooded and maintaining a 2 cm water level after germination in the control for duration of 21 days. We identified potential donors based on selection index computed from genomic estimated breeding values (GEBVs) using eight variables: germination at 14 DAS, germination at 21 DAS, seedling height at 14 DAS, seedling height at 21 DAS, shoot dry matter at 21 DAS, root dry matter at 21 DAS, culm diameter at 21 DAS, and root length at 21DAS. Ten genotypes emerged as the most promising, exhibiting at least 70% germination in floodwater at 21 DAS and greater selection indices. These genotypes were like: Afaa Mwanza 1/159, Rojomena 271/10, Kubwa Jinga, Wahiwahi, Magongo ya Wayungu, Mpaka wa Bibi, Mwangaza, Tarabinzona, IB126-Bug 2013A, and Kanamalia with respective percentages of 75, 74, 71, 86, 75, 80, 71, 80, 70, and 73. These findings contribute to global efforts to mitigate the impacts of flooding during germination. These donors, will be potential to enrich the gene pool for anaerobic germination, providing valuable resources for breeding for flooding tolerance.

12.
Violence Against Women ; : 10778012231203004, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37807754

RESUMO

We explore workplace sexual harassment (WSH) myth acceptance, bystander discomfort, and beliefs among farmworkers in California, USA, and Michoacán, Mexico. Surveys were conducted with the guidance of community advisory boards among 197 farmworkers (38 men and 59 women in California; 40 men and 60 women in Michoacán). Men and women in Michoacán had similar discomfort and myth acceptance. California women reported more discomfort than men but were similar in myth acceptance. The highest levels of myth acceptance ranged from 66 to 88%. The majority (85-90%) believed that something must be done to prevent WSH in agriculture.

13.
Ann Clin Lab Sci ; 53(6): 847-860, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38182140

RESUMO

OBJECTIVE: Frozen-section evaluation of the pancreatic margin is challenging. We aimed to determine interobserver variability among gastrointestinal pathologists for the assessment of frozen sections of pancreatic margins with marked chronic pancreatitis and to determine the challenging histological features in discrepant cases. METHODS: We identified 45 patients who underwent pancreas resection for pancreatic ductal adenocarcinoma and showed marked chronic pancreatitis at pancreatic margin. Deidentified first levels of frozen-sections of the pancreatic margins from all cases were independently reviewed by 5 experienced gastrointestinal pathologists for the presence of carcinoma and/or high-grade dysplasia. RESULTS: Interobserver agreement among pathologists was calculated as kappa coefficients ([Formula: see text]). A consensus diagnosis for discordant cases was obtained after group review and discussion. Interobserver agreement for adenocarcinoma diagnosis was 87%, and there was "substantial agreement" (Fleiss [Formula: see text]=0.78, P<0.01) and "almost perfect agreement" (Brennan-Prediger [Formula: see text]=0.86, P<0.01). Using the final diagnosis based on frozen and permanent sections as the gold standard and the concordant read of at least 3 of 5 pathologists for comparison, the diagnosis of adenocarcinoma was made in frozen-sections of pancreas margins, with accuracy 98%, sensitivity 83%, specificity 100%, negative predictive value 97%, positive predictive value 100%, false negative rate 9%, and false positive rate 0%. CONCLUSIONS: We showed excellent interobserver agreement among gastrointestinal pathologists for diagnosis of adenocarcinoma on frozen sections of pancreatic margins with marked chronic pancreatitis. Missed adenocarcinoma at the margin was mainly caused by freezing or cautery artifacts or by overlooking a tiny focus of perineural invasion in a background of marked chronic pancreatitis. The evaluation of deeper levels led to perfect agreement.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite Crônica , Humanos , Secções Congeladas , Variações Dependentes do Observador , Pancreatectomia , Pâncreas/cirurgia , Pancreatite Crônica/cirurgia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/cirurgia
14.
Front Public Health ; 11: 1268888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38328544

RESUMO

Background: Around 57,000 people in Spain and Portugal currently living with HIV or chronic hepatitis C are unaware of their infection. The COVID-19 pandemic severely disrupted screening efforts for these infections. We designed an intervention to increase and sustain opportunistic blood-borne virus (BBV) screening and linkage to care (SLTC) by implementing the TEST model. Methods: The Plan Do Study Act (PDSA) method of quality improvement (QI) was implemented in 8 healthcare organizations (HCOs), including four hospitals, two clusters of community health centers, and two community-based organizations (CBOs). Baseline assessment included a review of BBV SLTC practices, testing volume, and results 12 months before the intervention. Changes in BBV testing rates over time were measured before, during, and after the COVID-19 lockdowns in 2020. A mixed ANOVA model was used to analyze the possible effect on testing volumes among HCOs over the three study periods. Intervention: BBV testing was integrated into normal clinical flow in all HCOs using existing clinical infrastructure and staff. Electronic health record (EHR) systems were modified whenever possible to streamline screening processes, implement systemic institutional policy changes, and promote QI. Results: Two years after the launch of the intervention in screening practices, testing volumes increased by 116%, with formal healthcare settings recording larger increases than CBOs. The start of the COVID-19 lockdowns was accompanied by a global 60% decrease in testing in all HCOs. Screening emergency department patients or using EHR systems to automate screening showed the highest resilience and lowest reduction in testing. HCOs recovered 77% of their testing volume once the lockdowns were lifted, with CBOs making the fullest recovery. Globally, enhanced screening techniques enabled HCOs to diagnose a total of 1,860 individuals over the research period. Conclusions: Implementation of the TEST model enabled HCOs to increase and sustain BBV screening, even during COVID-19 lockdowns. Although improvement in screening was noted in all HCOs, additional work is needed to develop strong patient linkage to care models in challenging times, such as global pandemics.


Assuntos
COVID-19 , Infecções por HIV , Hepatite C , Programas de Rastreamento , Humanos , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hepatite C/diagnóstico , Infecções por HIV/diagnóstico , Pandemias , Portugal/epidemiologia , Melhoria de Qualidade , Espanha/epidemiologia , Programas de Rastreamento/estatística & dados numéricos
15.
Healthcare (Basel) ; 11(9)2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37174853

RESUMO

This study aimed to evaluate the effect of time on suicidal behavior, associated risk factors, and protective factors in early Mexican adolescents. Method: With a two-year longitudinal design, which included 18 of 34 adolescents who had previously participated in a DBT skills training program (DBT-PAHSE). The study evaluated ideation, suicide attempt, depression, emotional dysregulation, and psychological resources. Results: We observed differentiating significant differences over time in emotional dysregulation (F = 2.36 p = 0.04, η2= 0.12, ß = 0.72), affective resources (F = 3.94, p = 0.01, η2 = 0.18, ß = 0.82), and suicidal ideation. (F = 2.55, p = 0.03, η2= 0.13, ß = 0.77). In conclusion, the DBT-PAHSE program prevented deaths by suicide. It showed a reduction in emotional dysregulation up to two years after the end of treatment and maintained an increase in emotional and social resources. However, improvements are required to reduce depression over time and strengthen psychological resources.

16.
Clin Transl Oncol ; 25(10): 3021-3031, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37036596

RESUMO

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Trombose , Neoplasias da Bexiga Urinária , Tromboembolia Venosa , Humanos , Inibidores de Checkpoint Imunológico , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Bexiga Urinária , Oncologia , Neoplasias Renais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Albumina Sérica , Fatores de Risco
17.
BMC Med Genet ; 13: 58, 2012 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-22817530

RESUMO

BACKGROUND: Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. DESIGN AND METHODS: A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. RESULTS: Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI = 0.46-0.95); p = 0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI = 0.54-0.90); p = 0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI = 1.17-2.83); p = 0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI = 1.01-1.71); p = 0.043; additive model). After adjusting for multiple testing, results lost significance. CONCLUSION: Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.


Assuntos
Falência Renal Crônica/diagnóstico , Falência Renal Crônica/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Quimiocina CCL2/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Sistema Imunitário , Inflamação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Óxido Nítrico Sintase Tipo III/genética , Receptores de Interleucina-4/genética , Análise de Regressão , Estudos Retrospectivos , Fator de Transcrição STAT4/genética
18.
Cytokine ; 58(3): 321-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22433249

RESUMO

BACKGROUND: Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD). METHODS: A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches. RESULTS: From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033). CONCLUSION: Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.


Assuntos
Rejeição de Enxerto/genética , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Angiotensina/genética , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo
19.
Ann Clin Lab Sci ; 52(5): 838-842, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36261175

RESUMO

Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report a unique case of perineural invasion by IPMN in a 60-year-old female who underwent pancreatoduodenectomy for high-risk features of IPMN. Histological evaluation showed increased nerve density in the connective tissue of IPMN with multiple foci of perineural invasion by IPMN. In addition, there was a discrete 2 mm focus of invasive carcinoma that did not show perineural invasion. Chemotherapy was started and the patient is disease-free at 29 months follow up. The case illustrates previously unreported neuroplastic alterations and neutrotropism in benign neoplastic component of a malignant IPMN.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Adenocarcinoma Mucinoso/patologia , Pâncreas/patologia , Neoplasias Pancreáticas
20.
J Agric Saf Health ; 27(4): 229-247, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34729971

RESUMO

HIGHLIGHTS: Women and men farmworkers reported workplace sexual harassment (WSH). WSH occurred as frequently as daily. Both coworkers and leadership were perpetrators of WSH. ABSTRACT: This study explores experiences relevant to workplace sexual harassment (WSH) in agriculture among men and women farmworkers in California (U.S.) and Michoacán (Mexico). Anecdotal evidence documents women farmworkers having to endure behavioral, verbal, and physical WSH including sexual ogling, degrading language, groping, and requests for sex in exchange for work. We include survey comparisons between men and women in California and Michoacan on WSH among farmworkers. We conducted 197 farmworker surveys (38 men and 59 women in California; 40 men and 60 women in Michoacán). Community advisory boards contributed expertise and input for study strategies, materials, and dissemination. Survey participant ages ranged from 23 to 54 years old. Half worked in Mexico, 68% were married, 80% had children, and 47% had less than 7 years of education. Most farmworkers spoke Spanish and Purhépecha, an indigenous language spoken by the Purhépecha people in Michoacán. We used two strategies to measure WSH exposure in the previous year: (1) direct inquiry-based survey items (asking "Have you ever been the victim of or bystander to workplace sexual harassment?") documenting WSH among women (49%) and men (21%) in California and among women (7%) and men (13%) in Michoacán, and (2) behavior-based WSH items (using explicit examples of WSH behaviors perpetrated against the participant or witnessed by the participant as a bystander) documenting WSH among women (as high as 53%) and men (as high as 45%) in California and among women (as high as 65%) and men (as high as 68%) in Michoacán. Women farmworkers in California reported WSH experiences exceeding those of men. Reported WSH experiences in Michoacán were similar for men and women. Farmworkers identified WSH perpetrators as coworkers more than leadership. The frequency of exposure ranged from daily, weekly, monthly, and up to multiple times a year. Of 46 direct inquiry-based WSH incidents, only one perpetrator was punished, and at least half of all victims said they were forced to change their jobs. The findings of this study inform the development of WSH prevention efforts, such as education tools, support for efforts to facilitate reporting, protections against retaliation for workers, and promoting accountability for perpetrators. This information supports the promotion of policy recommendations and preventive approaches for WSH.


Assuntos
Fazendeiros , Assédio Sexual , Adulto , Agricultura , Criança , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Local de Trabalho , Adulto Jovem
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