Abstract Cathepsin D ( CTSD ) is a gene involved in amyloid precursor protein processing and is considered a candidate for Alzheimer's disease (AD). The aim of the current study was to examine if ...variation in CTSD increases the risk of AD. We performed a candidate-gene analysis in a population-based cohort study ( N = 7983), and estimated the effect of CTSD on the risk of AD. Additionally, a large meta-analysis was performed incorporating our data and previously published data. The T-allele of CTSD rs17571 was associated with an increased risk of AD ( p -value 0.007) in the Rotterdam Study. This association was predominantly found in APOE ε4 noncarriers. A meta-analysis of previously published data showed a significantly increased risk of AD in carriers of the T-allele of rs17571 (OR 1.22, 95% CI 1.03–1.44), irrespective of APOE ε4 carrier status. This study adds to the evidence that CTSD increases the risk of AD, although the effect size is moderate.
The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led ...to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants
. Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia
. Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
The clinical relevance of improved detection of cerebral microbleeds by using advanced-versus-conventional MR imaging techniques remains uncertain. As part of the population-based Rotterdam Scan ...Study, we compared whether participants whose microbleeds were only demonstrated on a high-resolution MR imaging sequence differed with respect to risk profile and risk of new microbleeds from participants whose microbleeds were also depicted on a conventional MR imaging sequence.
Two hundred participants (mean age, 79.2 years) underwent both conventional 2D T2*-weighted MR imaging and high-resolution 3D T2*-weighted MR imaging at 1.5T. Vascular risk factors, APOE allele status, and markers of small vessel disease and risk of incident microbleeds were compared for microbleed status by using logistic regression models adjusted for age and sex.
There were no significant associations between any of the factors and microbleed presence in participants whose microbleeds were only demonstrated on a high-resolution MR imaging sequence. However, the estimates in these participants were more similar to those in participants whose microbleeds were also depicted on a conventional MR imaging sequence than to those in participants without microbleeds. Moreover, significantly more participants whose microbleeds were only demonstrated on high-resolution MR imaging developed new CMBs during follow-up compared with participants without CMBs (25.0% versus 5.9%; OR, 5.98; 95% CI, 1.35-26.49).
Improved detection of microbleeds may contribute to more accurate identification of persons with underlying small-vessel pathology in the general elderly population. Further studies are needed to replicate these findings and firmly establish the role of improved detection of CMBs in the identification of persons with vasculopathy.
Peripheral neuropathies Hanewinckel, R; Ikram, M A; Van Doorn, P A
Handbook of clinical neurology,
2016, Letnik:
138
Journal Article
Recenzirano
Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and ...paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies.
Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of ...parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of parkinsonism, including Parkinson's disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of parkinsonism and Parkinson's disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident parkinsonism and Parkinson's disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed parkinsonism, of whom 47 developed Parkinson's disease. We showed that within the first 2 years of follow-up, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase 95% confidence interval (CI 0.91-6.23)} and shorter sleep duration HR 0.61 per standard deviation increase (95% CI 0.31-1.21) related to a higher risk of parkinsonism. Associations of worse sleep quality HR 3.86 (95% CI 1.19-12.47) and shorter sleep duration HR 0.48 (95% CI 0.23-0.99) with Parkinson's disease were more pronounced, and statistically significant, compared to parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality HR 1.76 per standard deviation increase (95% CI 1.12-2.78), as well as shortening of sleep duration HR 1.72 per standard deviation decrease (95% CI 1.08-2.72), were related to Parkinson's disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of parkinsonism, including Parkinson's disease.
The association between a smaller retinal arteriolar-to-venular ratio (AVR) and incident diabetes may be due to arteriolar narrowing, venular dilatation, or both. We investigated associations between ...baseline vessel diameters and incident impaired fasting glucose or diabetes in a population-based cohort (aged > or =55 years). Baseline retinal vessel diameters (1990-1993) were measured on digitized images of 2,309 subjects with a normal glucose tolerance test (postload glucose <7.8 mmol/l). At follow-up (1997-1999), impaired fasting glucose was defined as 6.1-7.0 mmol/l and diabetes as > or =7.0 mmol/l and/or antidiabetic medication use. Odds ratios (ORs) per SD increase in venular diameters were 1.13 (95% CI 1.00-1.29) for impaired fasting glucose and 1.09 (0.90-1.33) for diabetes. ORs per SD decrease in arteriolar diameters were 1.12 (0.98-1.27) and 1.08 (0.89-1.31) and per SD decrease in AVR were 1.29 (1.13-1.46) and 1.19 (0.98-1.45). After adjustment for cardiovascular risk factors, the associations were unaltered for venules and disappeared for arterioles. After stratification on age, associations between venular dilatation and impaired fasting glucose (1.23 1.02-1.47) or diabetes (1.18 0.89-1.56) were mainly present in participants aged <70 years. In conclusion, in our study, the risk of impaired fasting glucose and diabetes with AVR was explained by venular dilatation rather than arteriolar narrowing, warranting more focus on the causes of this dilatation.
Modern code reviews are supported by tools to enhance developers’ interactions allowing contributors to submit their opinions for each committed change in form of comments. Although the comments are ...aimed at discussing potential technical issues, the text might enclose harmful sentiments that could erode the benefits of suggested changes.
In this paper, we study empirically the impact of sentiment embodied within developers’ comments on the time and outcome of the code review process.
Based on historical data of four long-lived Open Source Software (OSS) projects from a code review system we investigate whether perceived sentiments have any impact on the interval time of code changes acceptance.
We found that (1) contributors frequently express positive and negative sentiments during code review activities; (2) the expressed sentiments differ among the contributors depending on their position within the social network of the reviewers (e.g., core vs peripheral contributors); (3) the sentiments expressed by contributors tend to be neutral as they progress from the status of newcomer in an OSS project to the status of core team contributors; (4) the reviews with negative comments on average took more time to complete than the reviews with positive/neutral comments, and (5) the reviews with controversial comments took significantly longer time in one project.
Through this work, we provide evidences that text-based sentiments have an impact on the duration of the code review process as well as the acceptance or rejection of the suggested changes.
Reduced graphene oxide-RGO was employed in various concentrations (2, 4, 6, 8) % to TiO2 nanoparticles using colloidal blending. X-ray diffraction (XRD) confirmed presence of anatase phase and ...improved crystallinity with doping. The presence of functional groups and Ti-O-Ti (∼500-600 cm−1) were confirmed by Fourier transform infrared spectroscopy (FTIR). The absorption increased upon doping gradually recorded via UV-visible spectroscopy. The Graphene oxide-GO/RGO sheets and irregular spherical morphologies were observed under transmission and field emission electron microscope respectively. Raman spectrums confirmed GO in TiO2 and RGO-TiO2 nanocomposite showed highest photocatalytic potential with graphene oxide (8% wt/wt). The higher photocatalytic activity of nanocomposites is mainly due to reduced graphene oxide (RGO) acted as electron acceptor, adsorbent and photosensitizer in dyes photodecomposition. It is noteworthy that RGO-TiO2 is beneficial and promising photocatalyst to clean the environment and wastewater.
Subjectively assessed health is related to mortality. Various subjective indicators of health have been studied, but it is unclear whether perceived physical functioning or mental health best ...accounts for the relation with mortality.
We studied the relation of subjective measures of health with all-cause mortality in 5538 participants of age 55 to 96 years at baseline from the Rotterdam Study. Various instruments of subjectively assessed health were used, that included basic activities of daily living (BADL), instrumental activities of daily living (IADL), quality of life (QoL), positive affect, somatic symptoms and negative affect. All participants completed questionnaires for each subjective measure of health and were followed for mortality for a mean of 12.2 (s.e. = 0.09) years. Cox regression analysis was conducted in the total sample.
In this cohort, 2021 persons died during 48 534 person-years of follow-up. All measures of subjective health were related to mortality after adjusting for age, gender, education, cognition, prevalent chronic diseases and cardiovascular risk BADL hazard ratio (HR, calculated per Z-score) = 1.35, 95% confidence interval (CI) 1.29-1.41; IADL HR = 1.27, 95% CI 1.22-1.32; QoL HR = 0.85, 95% CI 0.81-0.89; positive affect HR = 0.92, 95% CI 0.88-0.96; somatic symptoms HR = 1.11, 95% CI 1.06-1.16; and negative affect HR = 1.05, 95% CI 1.01-1.10. In the mutually adjusted model, only BADL (HR = 1.24, 95% CI 1.16-1.32) and IADL (HR = 1.10, 95% CI 1.04-1.17) remained independently associated with mortality.
Measures of subjectively assessed health are important indicators of mortality. Our study shows that of the different measures of subjective health, perceived physical health predicts mortality over and above mental health. Conversely, the association between mental health and mortality may partly be explained by poor perceived physical health.
Choriocarcinoma of the ovary is a rare neoplasm and tends to metastasize early to involve the lungs, brain, and liver. Metastasis to the gastrointestinal tract is rare. We report the case of a young ...lady, who presented with life-threatening gastrointestinal bleeding, secondary to jejunal involvement. The site of bleeding was localized using a computed tomography angiogram following inconclusive upper and lower gastrointestinal endoscopies. The bleeding jejunal segment was resected and the metastatic disease responded to combination chemotherapy. Metastatic choriocarcinoma of the ovary should be considered a possible diagnosis in patients presenting with gastrointestinal bleeding.
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