Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Participant Reactions to Two-Way Immersion (TWI) Programs

The purpose of this study was to elicit participant reactions to two-way immersion (TWI) programs in the United States of America. A large number of recent studies have focused on instructor views and perspectives of two-way immersion programs, so this study aimed to gain insight from students who are, or who have, participated in TWI programs throughout North America. One hundred fifty-one TWI schools throughout the United States were contacted and asked to participate in this study. Two similar surveys were developed, one for current TWI students, and another for former TWI students. Students from these two groups were asked to fill out a confidential online survey that addressed specific linguistic skills, abilities, and preferences, as well as connection to the cultures of the target language. Forty-eight percent of the survey respondents were native speakers of English, and the remaining 52% were non-native speakers of English. The number of respondents to the former student survey was so low that the data were inconclusive, and, therefore, will not be included in this study. Since the survey was conducted online, the data were stored in a comma-delimited format for further evaluation. The data were then tallied and analyzed for common themes

Experimental and field investigations of exposure, replication and transmission of SARS-CoV-2 in pigs in the Netherlands

In order to assess the risk of SARS-CoV-2 infection, transmission and reservoir development in swine, we combined results of an experimental and two observational studies. First, intranasal and intratracheal challenge of eight pigs did not result in infection, based on clinical signs and PCR on swab and lung tissue samples. Two serum samples returned a low positive result in virus neutralization, in line with findings in other infection experiments in pigs. Next, a retrospective observational study was performed in the Netherlands in the spring of 2020. Serum samples (N =417) obtained at slaughter from 17 farms located in a region with a high human case incidence in the first wave of the pandemic. Samples were tested with protein micro array, plaque reduction neutralization test and receptor-binding-domain ELISA. None of the serum samples was positive in all three assays, although six samples from one farm returned a low positive result in PRNT (titers 40-80). Therefore we conclude that serological evidence for large scale transmission was not observed. Finally, an outbreak of respiratory disease in pigs on one farm, coinciding with recent exposure to SARS-CoV-2 infected animal caretakers, was investigated. Tonsil swabs and paired serum samples were tested. No evidence for infection with SARS-CoV-2 was found. In conclusion, Although in both the experimental and the observational study few samples returned low antibody titer results in PRNT infection with SARS-CoV-2 was not confirmed. It was concluded that sporadic infections in the field cannot be excluded, but large-scale SARS-CoV-2 transmission among pigs is unlikely.info:eu-repo/semantics/publishedVersio

Exposure from the Chernobyl accident had adverse effects on erythrocytes, leukocytes, and, platelets in children in the Narodichesky region, Ukraine: A 6-year follow-up study

<p>Abstract</p> <p>Background</p> <p>After the Chernobyl nuclear accident on April 26, 1986, all children in the contaminated territory of the Narodichesky region, Zhitomir Oblast, Ukraine, were obliged to participate in a yearly medical examination. We present the results from these examinations for the years 1993 to 1998. Since the hematopoietic system is an important target, we investigated the association between residential soil density of ¹³⁷Caesium (¹³⁷Cs) and hemoglobin concentration, and erythrocyte, platelet, and leukocyte counts in 1,251 children, using 4,989 repeated measurements taken from 1993 to 1998.</p> <p>Methods</p> <p>Soil contamination measurements from 38 settlements were used as exposures. Blood counts were conducted using the same auto-analyzer in all investigations for all years. We used linear mixed models to compensate for the repeated measurements of each child over the six year period. We estimated the adjusted means for all markers, controlling for potential confounders.</p> <p>Results</p> <p>Data show a statistically significant reduction in red and white blood cell counts, platelet counts and hemoglobin with increasing residential ¹³⁷Cs soil contamination. Over the six-year observation period, hematologic markers did improve. In children with the higher exposure who were born before the accident, this improvement was more pronounced for platelet counts, and less for red blood cells and hemoglobin. There was no exposure×time interaction for white blood cell counts and not in 702 children who were born after the accident. The initial exposure gradient persisted in this sub-sample of children.</p> <p>Conclusion</p> <p>The study is the first longitudinal analysis from a large cohort of children after the Chernobyl accident. The findings suggest persistent adverse hematological effects associated with residential ¹³⁷Cs exposure.</p

Decline in age at menarche among Spanish women born from 1925 to 1962

<p>Abstract</p> <p>Background</p> <p>While the timing of reproductive events varies across populations, a downward trend in age at menarche has nevertheless been reported in most of the developed world over the past century. Given the impact of change in age at menarche on health conditions, this study sought to examine secular trends in age at menarche among women living in Navarre (Northern Spain) who participated in a population-based breast cancer screening programme.</p> <p>Methods</p> <p>The study was based on 110545 women born from 1925 to 1962. Trends were tested using a linear regression model, in which year of birth was entered continuously as the predictor and age at menarche (years) as the response variable, using size of town and region of birth as covariates.</p> <p>Results</p> <p>Among women born in Navarre between 1925 and 1962, age at menarche declined steadily from an average of 13.72 years in the 1925-1929 birth-cohorts to 12.83 years in the 1958-1962 birth-cohorts. Controlling for size of town or city of birth, age at menarche declined by an average of 0.132 years every 5 years over the period 1925-1962. This decline was greater in women born in rural versus urban settings. Trends were also different among regions of birth.</p> <p>Conclusion</p> <p>We report a population-based study showing a downward trend in age of onset of menarche among Spanish women born in the period 1925-1962, something that is more pronounced among women born in rural settings and varies geographically.</p

Posture Does Not Matter! Paw Usage and Grasping Paw Preference in a Small-Bodied Rooting Quadrupedal Mammal

BACKGROUND: Recent results in birds, marsupials, rodents and nonhuman primates suggest that phylogeny and ecological factors such as body size, diet and postural habit of a species influence limb usage and the direction and strength of limb laterality. To examine to which extent these findings can be generalised to small-bodied rooting quadrupedal mammals, we studied trees shrews (Tupaia belangeri). METHODOLOGY/PRINCIPAL FINDINGS: We established a behavioural test battery for examining paw usage comparable to small-bodied primates and tested 36 Tupaia belangeri. We studied paw usage in a natural foraging situation (simple food grasping task) and measured the influence of varying postural demands (triped, biped, cling, sit) on paw preferences by applying a forced-food grasping task similar to other small-bodied primates. Our findings suggest that rooting tree shrews prefer mouth over paw usage to catch food in a natural foraging situation. Moreover, we demonstrated that despite differences in postural demand, tree shrews show a strong and consistent individual paw preference for grasping across different tasks, but no paw preference at a population level. CONCLUSIONS/SIGNIFICANCE: Tree shrews showed less paw usage than small-bodied quadrupedal and arboreal primates, but the same paw preference. Our results confirm that individual paw preferences remain constant irrespective of postural demand in some small-bodied quadrupedal non primate and primate mammals which do not require fine motoric control for manipulating food items. Our findings suggest that the lack of paw/hand preference for grasping food at a population level is a universal pattern among those species and that the influence of postural demand on manual lateralisation in quadrupeds may have evolved in large-bodied species specialised in fine manipulations of food items

The JAK-STAT Pathway Controls Plasmodium vivax Load in Early Stages of Anopheles aquasalis Infection

Malaria affects 300 million people worldwide every year and 450,000 in Brazil. In coastal areas of Brazil, the main malaria vector is Anopheles aquasalis, and Plasmodium vivax is responsible for the majority of malaria cases in the Americas. Insects possess a powerful immune system to combat infections. Three pathways control the insect immune response: Toll, IMD, and JAK-STAT. Here we analyze the immune role of the A. aquasalis JAK-STAT pathway after P. vivax infection. Three genes, the transcription factor Signal Transducers and Activators of Transcription (STAT), the regulatory Protein Inhibitors of Activated STAT (PIAS) and the Nitric Oxide Synthase enzyme (NOS) were characterized. Expression of STAT and PIAS was higher in males than females and in eggs and first instar larvae when compared to larvae and pupae. RNA levels for STAT and PIAS increased 24 and 36 hours (h) after P. vivax challenge. NOS transcription increased 36 h post infection (hpi) while this protein was already detected in some midgut epithelial cells 24 hpi. Imunocytochemistry experiments using specific antibodies showed that in non-infected insects STAT and PIAS were found mostly in the fat body, while in infected mosquitoes the proteins were found in other body tissues. The knockdown of STAT by RNAi increased the number of oocysts in the midgut of A. aquasalis. This is the first clear evidence for the involvement of a specific immune pathway in the interaction of the Brazilian malaria vector A. aquasalis with P. vivax, delineating a potential target for the future development of disease controlling strategies

Municipal mortality due to thyroid cancer in Spain

BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor

Time trends in municipal distribution patterns of cancer mortality in Spain

BACKGROUND: New disease mapping techniques widely used in small-area studies enable disease distribution patterns to be identified and have become extremely popular in the field of public health. This paper reports on trends in the geographical mortality patterns of the most frequent cancers in Spain, over a period of 20 years. METHODS: We studied the municipal spatial pattern of stomach, colorectal, lung, breast, prostate and urinary bladder cancer mortality in Spain across four quinquennia, spanning the period 1989-2008. Case data were broken down by town (8073 municipalities), period and sex. Expected cases for each town were calculated using reference rates for each five-year period. For map plotting purposes, smoothed municipal relative risks were calculated using the conditional autoregressive model proposed by Besag, York and Mollié, with independent data for each quinquennium. We evaluated the presence of spatial patterns in maps on the basis of models, calculating the variance in relative risk corresponding to the structured spatial component and the unstructured component, as well as the proportion of variance explained by the structured spatial component. RESULTS: The mortality patterns observed for stomach, colorectal and lung cancer were maintained over the 20 years covered by the study. Prostate cancer and the tumours studied in women showed no defined spatial pattern, with the single exception of stomach cancer. The trend in spatial fractional variance indicated the possibility of a change in the spatial pattern in breast, bladder and colorectal cancer in women during the last five-year period. The paper goes on to discuss ways in which spatio-temporal data are depicted in the case of cancer, and review the risk factors that may possibly influence the respective tumours’ spatial patterns. CONCLUSION: In men, the marked geographical patterns of stomach, colorectal, lung and bladder cancer remained stable over time. Breast, colorectal and bladder cancer in women show signs of the possible appearance of a spatial pattern in Spain and should therefore be monitored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-535) contains supplementary material, which is available to authorized users

Is using the strengths and difficulties questionnaire in a community sample the optimal way to assess mental health functioning?

An important characteristic of a screening tool is its discriminant ability or the measure’s accuracy to distinguish between those with and without mental health problems. The current study examined the inter-rater agreement and screening concordance of the parent and teacher versions of SDQ at scale, subscale and item-levels, with the view of identifying the items that have the most informant discrepancies; and determining whether the concordance between parent and teacher reports on some items has the potential to influence decision making. Cross-sectional data from parent and teacher reports of the mental health functioning of a community sample of 299 students with and without disabilities from 75 different primary schools in Perth, Western Australia were analysed. The study found that: a) Intraclass correlations between parent and teacher ratings of children’s mental health using the SDQ at person level was fair on individual child level; b) The SDQ only demonstrated clinical utility when there was agreement between teacher and parent reports using the possible or 90% dichotomisation system; and c) Three individual items had positive likelihood ratio scores indicating clinical utility. Of note was the finding that the negative likelihood ratio or likelihood of disregarding the absence of a condition when both parents and teachers rate the item as absent was not significant. Taken together, these findings suggest that the SDQ is not optimised for use in community samples and that further psychometric evaluation of the SDQ in this context is clearly warranted