Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare form of nonhypertensive cerebral small-vessel disease caused by mutations in the HTRA1 ...gene. CARASIL is characterized by early adulthood onset of subcortical infarcts, cognitive impairment, alopecia, and spondylosis. Until recently, this disorder was almost exclusively reported in the Asian population.
Description of the clinical, imaging, and genetic study of 2 siblings with CARASIL, with a brief comparative review of published non-Asian cases of the disease.
Both patients exhibited the typical phenotype: cerebral small-vessel disease, spondylosis, and abnormal hair lost. Mutation screening was performed for NOTCH3 and HTRA1 genes. No mutations were found in NOTCH3. The study revealed the presence of a homozygous c.496C>T substitution in HTRA1 in both siblings.
This report highlights the need of considering this entity in the differential diagnosis of cerebral small-vessel disease in young patients, even in the non-Asian populations.
The whale-watching industry can represent a critical anthropogenic stressor for the targeted populations. Identifying and characterizing the individual exposure to wildlife tourism in ...island-associated cetacean communities is especially relevant in small, remote oceanic regions relying on tourism. This study characterized the spatial and temporal variation of the whale-watching pressure on common bottlenose dolphins (Tursiops truncatus) and short-finned pilot whales (Globicephala macrorhynchus) in Madeira Island and identified the most exposed portion of the population, making use of diverse long-term datasets (i.e. sighting data, photographic data and vessels’ tracks) obtained year-round from platforms of opportunity (whale-watching operators) and proposing a new descriptive index which estimates the cumulative exposure rates. Core areas of encounters with the whale-watching vessels were identified off the capital city of Funchal. A daily average of 6.5 (±2.2 SD) vessels were concurring in this area, with a significantly higher number recorded between May and October and a peak of 14 vessels in August. From a total of 367 identified bottlenose dolphins and 536 pilot whales, a minimum of 6% and 10%, respectively, were identified as island-associated individuals. Cumulative exposure rates for these individuals could reach levels over two times higher than the general trend for both species. A higher proportion of island-associated bottlenose dolphins were recorded in the winter season. In contrast, island-associated pilot whales were predominant (over 50%) or in a high proportion (over 40%) year-round. The present study highlights the importance of using data from platforms of opportunity to investigate anthropogenic stressors, as tourism-based cetacean observation. It also provides insights into the whale-watching pressure on island-associated individuals occurring in oceanic areas and calls attention to the need of monitoring the fitness and well-being of these wildlife populations in Madeira Archipelago, an outermost European region.
•A new method based on photographic recaptures is used to estimate the individual exposure of cetaceans to whale-watching.•Cores areas of boat-cetacean encounters (50% Kernel Density Estimation) were identified.•Cumulative exposure rates for island-associated individuals are over two times higher than the general trend.•Seasonal analysis showed a high proportion of island-associated pilot whales exposed throughout the year.•Opportunistic data can effectively contribute to the monitoring of tourism-based cetaceans’ observation activity.
Introduction: Existing literature presents varying perspectives on the impact of COVID-19 on liver transplant recipients. However, no research has specifically investigated the role of gender ...differences in the manifestation of COVID-19 among liver transplant recipients. This study aims to examine the effects of COVID-19 on liver transplant recipients, with a focus on gender differences in disease presentation and progression. Methods: Conducted as a multicenter historical cohort study, this research collected patient records through an online questionnaire. Assessing COVID-related mortality was the main objective. Additionally, demographic, clinical, and laboratory data pertaining to disease presentation and progression were collected. Results:The study included a total of 283 patients, of whom 76 were female and 206 were male. The median follow-up period for males was 99 days (IQR 38-283), while for females, it was 126 days (IQR 44-291). A higher prevalence of cardiovascular disease was observed in males (p=0.002). Females frequently experienced a loss of smell (p=0.021), whereas males commonly exhibited fever (p=0.031). Levels of ALT and gamma-glutamyl transferase were significantly elevated in males (p=0.008 and 0.004, respectively). Although there was a trend towards increased mortality in males, it did not reach statistical significance.Conclusion: This study is the first attempt to investigate gender differences in COVID-19 among liver transplant recipients. Our findings highlight the need for a comprehensive and personalised approach to treating this patient population and underscore the importance of further elucidating the disease presentation in these individuals
Endovascular aneurysm repair (EVAR) became an increasingly preferred modality for abdominal aortic aneurysm (AAA) repair both in elective AAA repair (el-EVAR) and EVAR of a ruptured AAA (r-EVAR) ...setting. Ruptured AAAs usually have more hostile anatomies and less time for planning. Consequently, more complications may arise after r-EVAR. The purpose of this study was to compare mi-term outcomes between r-EVAR and el-EVAR.
A retrospective cohort analysis of patients undergoing EVAR from 2000 to 2015 at a tertiary institution was performed. Patients with previous aortic surgery, nonatherosclerotic AAA and isolated iliac aneurysms were excluded. In-hospital casualties or patients who were intraoperatively converted to open repair were also excluded. For the midterm outcome analysis, only patients with at least two postoperative examinations (a 30-day computed tomography scan and a second postoperative examination performed 6 months or later) were considered. The primary end point was freedom from aneurysm-related complications (a composite of type I or III endoleak, aneurysm sac growth, migration of more than 5 mm, device integrity failure, AAA-related death, late postimplant rupture, or AAA-related secondary intervention). Freedom from secondary interventions, neck-related events (defined as a composite of type IA endoleak, migration of more than 5 mm, or preemptive neck-related secondary intervention) and late survival were secondary end points. The impact of device instructions for use (IFU) compliance on neck events was also assessed.
The study included 565 patients (65 r-EVAR and 500 el-EVAR). Eighty-two patients were treated outside proximal neck IFU, 13 in the r-EVAR group (21.3%) and 69 (14.5%) in the el-EVAR (P = .16). During the index hospitalization, there were more complications (12.3% vs 3.2%; P = .001) and reinterventions (12.3% vs 2.8%; P < .001) in the r-EVAR group. After discharge, median clinical follow-up time was 4.3 years (interquartile range, 2.1-7.0 years) without differences between both groups. Five-year freedom from AAA-related complications was 53.9% in the r-EVAR group and 65.4% in the el-EVAR (P = .21). In multivariable analysis the r-EVAR group was not at increased risk for late complications (hazard ratio HR, 0.94; 95% confidence interval CI, 0.54-1.61; P = .81). Five-year freedom from neck-related events was 74% in r-EVAR and 82% in the el-EVAR group (P = .345). Patients treated outside neck IFU were at greater risk for neck-related events both in r-EVAR (HR, 6.5; 95% CI, 1.8-22.9; P = .004) and el-EVAR group (HR, 2.6; 95% CI, 1.5-4.5; P < .001). Freedom from secondary interventions at 5 years was 63.0% for r-EVAR and 76.9% for el-EVAR (P = .16). Survival at 5 years was 68.8% in the r-EVAR group and 73.3% in the el-EVAR group (P = .30).
Durable and sustainable midterm outcomes were found for both r-EVAR and el-EVAR patients who survived the postoperative period. Patients treated outside the IFU are at greater risk for late complications. Surveillance protocols may be tailored according to individual anatomy and IFU compliance rather than timing of repair.
O artigo relaciona os elementos curriculares propostos por Hobbes no capítulo XXX do Leviatã com as leis naturais descritas nos capítulos XIV e XV. Metodologicamente, o trabalho conduz-se em 4 ...etapas: 1) listar os conteúdos educacionais explicitados no capítulo XXX; 2) buscar potenciais equivalentes de cada um dos conteúdos listados com aspectos das leis naturais presentes nos capítulos XIV e XV; 3) comparar os argumentos e questões teóricas pertinentes a essas equivalências potenciais; 4) destacar possíveis ampliações interpretativas oriundas da análise comparativa realizada. Dada essa escolha metodológica, justifica-se a ausência de outras referências bibliográficas que não o Leviatã. Dentre os achados, sublinha-se que todos elementos curriculares presentes no capítulo XXX puderam ser articulados com, pelo menos, uma lei natural, merecendo destaque a maior ocorrência de vinculações com a terceira lei de natureza.
Introduction: With the worldwide decline on male fertility potential, the importance of the insight of the spermatogenic process has been increasing. In recent years, proteomic methodologies have ...been applied to seminal fluid of infertile men to search for infertility potential biomarkers. However, to understand the spermatogenic event and to search for treatment to spermatogenic impairment, comparative analysis of testicular proteomics is considered a powerful methodology.
Areas covered: Herein, we present a critical overview of the studies addressing proteomic alterations in the development of spermatogenesis during puberty, as well as during the different phases of the spermatogenic event. The comparative studies of the proteomic testicular profile of men with and without spermatogenic impairment are also discussed and key proteins and pathways involved highlighted.
Expert opinion: The usage of whole human testicular tissue with its heterogeneous cellular composition makes proteome data interpretation particularly challenging. This may be minimized by controlled experiments involving the collection of testicular tissue and sperm from the same individuals, integrated in a clinically characterized cohort of healthy and infertile men. The analysis of specific subcellular proteomes can add more information to the proteomic puzzle, opening new treatment possibilities for infertile/subfertile men.
The growing incidence of prostate cancer has prompted a great investment in basic biology and translational studies to develop new therapies. Multiple animal models have been established to study ...etiological factors, cancer-preventive strategies and the molecular determinants of aggressiveness and metastases. The rat model of prostate cancer induced by chemical carcinogen N-methyl-N-nitrosourea (MNU) and testosterone exposure has become an important tool to study prostatic carcinogenesis and chemopreventive approaches. Over prolonged treatment, this model develops prostatic lesions that closely mimic those observed in human patients. By modifying the experimental conditions, different research groups have been able to induce a vast spectrum of lesions, ranging from early prostatic intraepithelial neoplasia to metastatic cancer. These carefully tuned experimental settings allowed researchers to test lifestyle interventions, and different pharmacological and chemopreventive strategies. However, this model's great flexibility requires careful planning to ensure that the experimental conditions are adequate to obtain the spectrum of lesions intended. The present review addresses such issues, highlighting the value of the rat prostate cancer model and the multiple challenges and opportunities it offers to researchers worldwide.
Abstract Access to health care is a sensitive issue in low population density territories, as these areas tend to have a lower level of service provision. One dimension of access is accessibility. ...This paper focuses on measuring the accessibility to urgent and emergency care services in the Portuguese region of Baixo Alentejo, a territory characterized by low population density. Data for the calculation of accessibility is the road network, and the methodology considers the application of a two-level network analyst method: time-distance by own mean (car or taxi) to the urgent care services and the time distance to emergency services as a way to get assistance and to go to urgent care services. While urgent care accessibility meets the requirements stipulated in the Integrated Medical Emergency System’s current legislative framework, the simulation of different scenarios of potential accessibility shows intra-regional disparities. Some territories have a low level of accessibility. Older adults, the poorly educated, and low-income population, also have the lowest levels of accessibility, which translates into dually disadvantageous situation since the potential users of emergency services are most likely to belong to this group of citizens.
Resumo Em territórios de baixa densidade populacional, o acesso aos cuidados de saúde é uma questão delicada, pois essas áreas tendem a ter um nível mais baixo de prestação de serviços. Uma dimensão do acesso é a medição da acessibilidade. Este artigo tem como propósito medir a acessibilidade aos serviços de urgência e aos meios de emergência médica na região portuguesa do Baixo Alentejo, território caracterizado por uma baixa densidade populacional. A metodologia considera o método network analyst aplicado à rede viária, em dois níveis: o cálculo da distância-tempo aos serviços de urgência usando modo próprio (carro ou táxi); e o cálculo da distância-tempo recorrendo aos meios de socorro e emergência como forma de aceder aos serviços de urgência. Embora se considere que a acessibilidade às urgências atende ao atual quadro legislativo do Sistema Integrado de Emergência Médica, a simulação de diferentes cenários no Baixo Alentejo mostra a existência de disparidades intra-regionais no que se refere à acessibilidade aos serviços de urgência. Verifica-se que é a população idosa, de baixa instrução e residente em zonas com baixa densidade populacional quem apresenta menores índices de acessibilidade, o que traduz uma situação duplamente desvantajosa, uma vez que estes são os maiores utilizadores destes serviços.
Cancer cachexia is a highly complex multifactorial disorder that is often misdiagnosed, leading to suboptimal health outcomes. Indeed, cachexia is a concern in cancer, typifying lower response to ...treatment and risk of death. Thus, efforts have been made to better understand the molecular basis of this syndrome, envisioning to improve its diagnosis and management. C-reactive protein (CRP) has been reported to be consistently increased in the circulation of patients with body wasting associated to chronic diseases. However, the role of CRP in the pathogenesis of cachexia remains elusive. Several hypotheses have been advanced but most of experimental findings support an indirect effect on the activation of muscle proteolysis, mostly through its interplay with pro-inflammatory cytokines. Herein, we overview the contribution of CRP to body wasting and its putative biomarker value for the diagnosis and follow-up of the therapeutic management of cachexia.
Fertility rates in developing countries have declined over the past decades, and the trend of delayed fatherhood is rising as societies develop. The reasons behind the decline in male fertility with ...advancing age remain mysterious, making it a compelling and crucial area for further research. However, the limited number of studies dedicated to unraveling this enigma poses a challenge. Thus, our objective is to illuminate some of the upregulated and downregulated mechanisms in the male testis during the aging process.
Herein, we present a critical overview of the studies addressing the alterations of testicular proteome through the aging process, starting from sexually matured young males to end-of-life-expectancy aged males. The comparative studies of the proteomic testicular profile of men with and without spermatogenic impairment are also discussed and key proteins and pathways involved are highlighted.
The difficulty of making age-comparative studies, especially of advanced-age study subjects, makes this topic of study quite challenging. Another topic worth mentioning is the heterogeneous nature and vast cellular composition of testicular tissue, which makes proteome data interpretation tricky. The cell type sorting and comorbidities testing in the testicular tissue of the studied subjects would help mitigate these problems.
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