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1.
Curr Pharm Des ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013825

RESUMO

BACKGROUND: Frail individuals experience an accelerated immunosenescence, and exercise has been identified as a therapy to promote a better inflammatory environment. OBJECTIVE: To analyze the effects of 28-weeks of two different exercise protocols on the functional fitness and immune profiles of institutionalized pre-frail and frail women with mild cognitive impairment. METHODS: Participants residing in care homes (n=60, 81±7.84 years old) were randomized into three groups: a chair elastic band muscle-strength exercise (CSE, n=21; 81±4.79), a chair multimodal exercise (CME, n=20; 80±8.19) and a control non-exercise (CGne, n=19; 80±10.01). Both CME and CSE groups performed progressive circuit-training exercise sessions. The controls did not change their usual lifestyle. The Fried protocol and the Mini Mental State Examination questionnaire were used to identify the frail subgroups and the participants with mild cognitive impairment. Data for anti and pro-inflammatory markers and physical fitness were analyzed pre and post-interventions. RESULTS: After the intervention, a significant effect of time and time by group for sIgA and time by group for IL-10 levels were found (p > 0.05). Within-group analysis showed a significant moderate decrease in the TNF-α to IL-10 ratio for the CME group and an increase in the controls (p > 0.05) and a slight reduction in the IL-6 and IL-1ß concentrations. The controls showed a negative trend towards a decrease in physical fitness and a trend for increased levels in the pro-inflammatory markers IL-6 and IL-1ß. CONCLUSIONS: The evidence regarding the use of systematic and moderate long-term exercise as therapy for promoting a better balance between pro- and anti-inflammatory environments and a decrease in the inflammatory index for the CME group were the most promising results from this study.

2.
Carbohydr Polym ; 231: 115703, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888825

RESUMO

De-Man Rogosa and Sharpe (MRS) is a complex medium commonly used to obtain exopolysaccharides (EPS) from lactic acid bacteria. However, the various nutrients (carbon and nitrogen sources) of media and supplements added to enhance the bacterial growth and EPS production, may interfere with the purification of the extracts resulting in an over-estimation of the EPS and erroneous structural assignments. The efficiency of trichloroacetic acid (TCA)/pronase and 5-sulfosalicylic acid - SSA methods was evaluated. In addition, the interference of the major MRS broth components as well as lactose was evaluated using xanthan gum as model control EPS. It was concluded that MRS medium is a major source of interfering compounds in the quantification of EPS, mainly glucose-rich material and to a lesser extent mannoproteins from yeast extract. This effect was found to be potentiated by the presence of lactose. TCA/pronase method was shown to be more efficient in eliminating interferents.

3.
Braz J Microbiol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953649

RESUMO

An unprecedented outbreak of rabies occurred in Rio Grande do Sul state (RS) from 2012 onward, resulting in thousands of bovine deaths, important economic losses, and posing risk to human health. This article describes a genetic analysis of 145 rabies viruses (RABV) recovered from herbivorous from RS between 2012 and 2017, based on partial sequence analysis of the nucleoprotein (N) gene. High nucleotide (nt) identity (95.5 to 100%) and amino acid (aa) similarity (96.7 to 100%) were observed among the analyzed sequences. These sequences displayed a high sequence nt identity/aa similarity with bovine RABV sequences (96.4-97.9%; 98.1-100%, respectively) and vampire bat RABV sequences (96.3-97.5%; 97.8-99.5%). Phylogenetic analyzes based on the N sequence allowed for the segregation of viruses into two distinct clusters. Cluster 1 comprised RABV sequences covering the whole studied period, whereas cluster 2 grouped a lower number of viruses from 2013, 2014, 2015, to 2017. In some cases, viruses obtained from the same region within a short period of time grouped to distinct clusters or sub-clusters, indicating the co-circulation of distinct virus lineages in these outbreaks. The segregation into sub-clusters was also observed for viral sequences obtained from the same region at different times, indicating the involvement of distinct viruses. In summary, partial sequence analyses revealed a high conservation of N protein and the circulation of two lineages and different sublineages of RABV in the region. In addition, our results confirm the suitability of N gene to study the genetic relationships among RABV isolates.

4.
Virus Genes ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955384

RESUMO

Bats and dogs are the main reservoirs of rabies virus (RABV) in Latin America and are responsible for the maintenance of different cycles of infection. In the two neighbour and most southern Brazilian states of Rio Grande do Sul (RS) and Santa Catarina (SC), rabies in dogs has been successfully controlled for more than 30 years. However, rabies associated to the rural cycle remains endemic, with a significant, though oscillating-annual incidence of rabies in cattle. Despite the plethora of studies on genetic analyses of Brazilian RABV, isolates from southern Brazil have only scarcely been investigated. This work was performed to identify the genetic lineages of RABVs circulating in states of RS and SC. Fifty-nine RABV cattle isolates from RS and SC were selected and submitted to reverse transcription/polymerase chain reaction (RT-PCR) followed by sequencing of the nucleoprotein gene. In RS, the circulation of two sublineages (1A and 1B) of RABV was detected, both with characteristics of lineages usually detected in vampire bats (Desmodus rotundus). In SC, only one sublineage of RABV (1B) was detected. Nevertheless, the findings reported here are expected to contribute to the understanding of the biology of the virus in the region and its interactions with the natural host D. rotundus.

5.
Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

6.
Exp Gerontol ; 130: 110790, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31816425

RESUMO

PURPOSE: Many people experience aging-related losses in different physical domains, which leads to a condition often called physical frailty (PF). The aim of this study was to analyse the effects of two different, 28-weeks, class chair-exercise protocols on salivary steroid hormones (SH), PF, and functional disabilities (FD) in frail older women. METHODS: A sample of older frail individuals (n = 60, 817.84 years) participated in the study and were divided into three groups: chair elastic-band muscle strength exercises (CSE), n = 20), chair-multimodal exercise (CME, n = 21) and a control non-exercise group (CGne, n = 19). Both exercise programs consisted of 45 min of supervised chair-based exercise group classes, carried out 3 times/week. CME participants performed a progressive training using walking, mobility and body weight resistance exercises. The CSE participants exercised using an elastic-band system of progressive exercises. Both CSE and CME followed a circuit training protocol. The controls did not change their usual lifestyle. The indicators of PF, FD and SH concentrations were analyzed before and after the intervention. RESULTS: Both exercise programs diminished the PF status showing significant time and time versus treatment interactions (p < .01). An increase in the CME group, between baseline and 14-weeks, and in the CSE group, after 28 weeks, for Testosterone concentrations was observed (p < .01). Dehydroepiandrosterone (DHEA) increased after 28-weeks in the CME group and decreased in the CGne after the same period (p < .05). Both exercise programs decreased the negative scores of several FD domains, specially fear of falling that showed significant effects with time (p < .01), and time vs intervention (p < .05). CONCLUSION: Both chair-exercise based programs were effective in stimulating positive changes in physical health and in steroid hormone responses, especially in DHEA. The control group did show a negative trend towards an increased PF status and decreased levels of SH. It is crucial for public health to identify the main factors associated with Functional Disability and Physical Frailty that underlie the development of new methods for complementary therapies, such as the use of low doses of hormonal supplementation combined with long-term exercise interventions.

7.
Genome Biol Evol ; 12(1): 3656-3662, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834364

RESUMO

Hares (genus Lepus) provide clear examples of repeated and often massive introgressive hybridization and striking local adaptations. Genomic studies on this group have so far relied on comparisons to the European rabbit (Oryctolagus cuniculus) reference genome. Here, we report the first de novo draft reference genome for a hare species, the mountain hare (Lepus timidus), and evaluate the efficacy of whole-genome re-sequencing analyses using the new reference versus using the rabbit reference genome. The genome was assembled using the ALLPATHS-LG protocol with a combination of overlapping pair and mate-pair Illumina sequencing (77x coverage). The assembly contained 32,294 scaffolds with a total length of 2.7 Gb and a scaffold N50 of 3.4 Mb. Re-scaffolding based on the rabbit reference reduced the total number of scaffolds to 4,205 with a scaffold N50 of 194 Mb. A correspondence was found between 22 of these hare scaffolds and the rabbit chromosomes, based on gene content and direct alignment. We annotated 24,578 protein coding genes by combining ab-initio predictions, homology search, and transcriptome data, of which 683 were solely derived from hare-specific transcriptome data. The hare reference genome is therefore a new resource to discover and investigate hare-specific variation. Similar estimates of heterozygosity and inferred demographic history profiles were obtained when mapping hare whole-genome re-sequencing data to the new hare draft genome or to alternative references based on the rabbit genome. Our results validate previous reference-based strategies and suggest that the chromosome-scale hare draft genome should enable chromosome-wide analyses and genome scans on hares.

8.
Women Health ; 60(2): 140-155, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31154915

RESUMO

Little is known about symptoms associated with frailty in institutionalized Portuguese older adults. This study aimed to investigate the association of frailty with diverse geriatric health characteristics. Cross-sectional data from 140 women aged between 75 and 85 years were analyzed. Data were collected between March and June, 2016. Fried's definition of physical frailty, psychological, sex hormones, disability and physical fitness outcomes were examined. The prevalence of frailty was 40%. Frail women had lower scores in cognitive and physical fitness, and higher scores for depressive symptoms and comorbidities. Significant correlations emerged between frailty and disability, fear of falling, aerobic resistance and cognition. Regression analyses and Receiver Operating Only aerobic resistance (sensitivity [93-96%]; specificity [74-77%], p = .001) and cognition (sensitivity [77-88%]; specificity [65-71%], p < .001) remained in the equation as independently related to physical frailty. A trend of significant differences in lower systolic blood pressure may reflect being less physically active and/or having more systemic comorbidity. Fried's model can be considered applicable. The 2-minute step test and the Mini Mental State Examination could better identify frail populations. The role of blood pressure and level of education in physical frailty status needs to be further explored.

9.
J Pharm Biomed Anal ; 178: 112939, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31672579

RESUMO

Substandard and falsified medical products may cause harm to patients and fail to treat the diseases or conditions for which they were intended. It is therefore required to have analytical methods available to assess medical product quality. Benchtop NMR spectroscopy provides a generic, inherently quantitative, analytical method capable of separating specific signals from those of a matrix. We have developed an analytical method for the analysis of active ingredients in pharmaceutical products and illegal drugs, based on benchtop NMR spectroscopy. Within its resolution limits, benchtop NMR spectroscopy is useful in determining the identity of the active ingredients in products containing acetaminophen, aspirin, caffeine, diclofenac, ibuprofen, naproxen, sildenafil, tadalafil and sibutramine, cocaine, and gamma hydroxybutyric acid, with a limit of detection of about 1 mg/mL. Furthermore, the content of the active ingredient can be determined with an error of 10%. Additionally, a chemometrics approach is shown to be useful to classify spectra in order to identify the active substances present in the sample, reducing the need for expert interpretation of the spectra acquired.

10.
Exp Gerontol ; 129: 110759, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678219

RESUMO

Identification of older populations at increased risk of physical frailty using biochemical approaches could improve screening accuracy. The aim of this study was to study the relationship between immune markers and independent components of physical frailty in institutionalized older women. A sample of 358 institutionalized-dwelling women, aged 75 years and older, were assessed for biosocial factors and general health status, pro and anti-inflammatory cytokines, sex steroid hormones, salivary anti-microbial proteins, blood cells counts and the five Fried's physical frailty components that allowed for classification of the sample into frail, prefrailty and not-frail subgroups. Results showed that cytokines IL-6, IL-10, IL-1ß, TNF-α, and the TNF-α/IL-10 ratio, mean corpuscular haemoglobin, salivary cortisol and α-amylase were all associated with frailty. Weakness and Exhaustion were the frailty components that were most strongly associated with these biomarkers. Salivary α-amylase was the biomarker that best explained frailty, as it was associated with all five components of physical frailty, and could be used as a potential screening tool. Future research needs to investigate the causal-effect association between salivary innate immune makers, susceptibility to infection and frailty.

11.
Toxicol In Vitro ; 62: 104718, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706955

RESUMO

Ketamine is a potent uncompetitive NMDA receptor antagonist that provides amnesia, analgesia, environmental dissociation and immobility, where it has its cytotoxic effect well described in the literature. However, the work on its genotoxic/mutagenic potentials are scarce and insufficient and does not allow a reasonable evaluation of its role. Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. Our data revealed that ketamine induces a weak cytotoxic effect on human PBLs after 24 h and is devoided of hemolytic effects. A small amount of DNA strand breaks levels were detected in the modified comet assay (employment of FPG enzyme) only at highest concentrations (500 and 700 µg/mL) of ketamine, highlighting our pro-oxidant data regarding ketamine. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000 µg/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models.

12.
Exp Gerontol ; 131: 110816, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31862421

RESUMO

Gait parameters have been investigated as an additional tool for differential diagnosis in neurocognitive disorders, especially among healthy elderly (HE), those with mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients. A videogrammetry system could be used as a low-cost and clinically practical equipment to capture and analyze gait in older adults. The aim of this study was to select the better gait parameter to differentiate these groups among different motor test conditions with videogrammetry analyses. Different motor conditions were used in three specific assessments: 10-meter walk test (10mWT), timed up and go test (TUGT), and treadmill walk test (TWT). These tasks were compared among HE (n=17), MCI (n=23), and AD (n=23) groups. One-way ANOVA, Kruskal-Wallis, and Bonferroni post-hoc tests were used to compare variables among groups. Then, an effect size (ES) and a linear regression analysis were calculated. The gait parameters showed significant differences among groups in all conditions, but not in TWT. Controlled by confounding variables, the gait velocity in 10mWT at usual speed, and TUGT in dual-task condition, predicts 39% and 53% of the difference among diagnoses, respectively. Finally, these results suggest that a low-cost and practical video analysis could be able to differentiate HE, those with MCI, and AD patients in clinical assessments.

13.
BMC Evol Biol ; 19(1): 221, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791244

RESUMO

BACKGROUND: Toll-like receptors (TLRs) are the most widely studied innate immunity receptors responsible for recognition of invading pathogens. Among the TLR family, TLR5 is the only that senses and recognizes flagellin, the major protein of bacterial flagella. TLR5 has been reported to be under overall purifying selection in mammals, with a small proportion of codons under positive selection. However, the variation of substitution rates among major mammalian groups has been neglected. Here, we studied the evolution of TLR5 in mammals, comparing the substitution rates among groups. RESULTS: In this study we analysed the TLR5 substitution rates in Euungulata, Carnivora, Chiroptera, Primata, Rodentia and Lagomorpha, groups. For that, Tajima's relative rate test, Bayesian inference of evolutionary rates and genetic distances were estimated with CODEML's branch model and RELAX. The combined results showed that in the Lagomorpha, Rodentia, Carnivora and Chiroptera lineages TLR5 is evolving at a higher substitution rate. The RELAX analysis further suggested a significant relaxation of selective pressures for the Lagomorpha (K = 0.22, p < 0.01), Rodentia (K = 0.58, p < 0.01) and Chiroptera (K = 0.65, p < 0.01) lineages and for the Carnivora ancestral branches (K = 0.13, p < 0.01). CONCLUSIONS: Our results show that the TLR5 substitution rate is not uniform among mammals. In fact, among the different mammal groups studied, the Lagomorpha, Rodentia, Carnivora and Chiroptera are evolving faster. This evolutionary pattern could be explained by 1) the acquisition of new functions of TLR5 in the groups with higher substitution rate, i.e. TLR5 neofunctionalization, 2) by the beginning of a TLR5 pseudogenization in these groups due to some redundancy between the TLRs genes, or 3) an arms race between TLR5 and species-specific parasites.


Assuntos
Evolução Molecular , Mamíferos/genética , Receptor 5 Toll-Like/genética , Animais , Teorema de Bayes , Códon , Flagelina/metabolismo , Humanos , Imunidade Inata , Mamíferos/imunologia , Filogenia , Especificidade da Espécie , Receptor 5 Toll-Like/química , Receptor 5 Toll-Like/imunologia
14.
Front Neurol ; 10: 1182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798515

RESUMO

Introduction: The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to provide insights into the clinical characteristics of patients with Tuberous Sclerosis Complex (TSC). The aims of this study were to identify issues that arose during the design, execution, and publication phases of TOSCA, and to reflect on lessons learnt that may guide future registries in rare and complex diseases. Methods: A questionnaire was designed to identify the strengths, weaknesses, and issues that arose at any stage of development and implementation of the TOSCA registry. The questionnaire contained 225 questions distributed in 7 sections (identification of issues during registry planning, during the operation of the registry, during data analysis, during the publication of the results, other issues, assessment of lessons learnt, and additional comments), and was sent by e-mail to 511 people involved in the registry, including 28 members of the Scientific Advisory Board (SAB), 162 principal investigators (PIs), and 321 employees of the sponsor belonging to the medical department or that were clinical research associate (CRA). Questionnaires received within the 2 months from the initial mailing were included in the analysis. Results: A total of 53 (10.4%) questionnaires were received (64.3% for SAB members, 12.3% for PIs and 4.7% for employees of the sponsor), and the overall completeness rate for closed questions was 87.6%. The most common issues identified were the limited duration of the registry (38%) and issues related to handling of missing data (32%). In addition, 25% of the respondents commented that biases might have compromised the validity of the results. More than 80% of the respondents reported that the registry improved the knowledge on the natural history and manifestations of TSC, increased disease awareness and helped to identify relevant information for clinical research in TSC. Conclusions: This analysis shows the importance of registries as a powerful tool to increase disease awareness, to produce real-world evidence, and to generate questions for future research. However, there is a need to implement strategies to ensure patient retention and long-term sustainability of patient registries, to improve data quality, and to reduce biases.

15.
Epilepsia ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876960

RESUMO

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

16.
Stem Cells Int ; 2019: 7951696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781247

RESUMO

Background: A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells-autologous cells obtained from tissues such as bone marrow and fat-combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. Methods: Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. Results: The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. Conclusion: These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.

17.
Genet Med ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680122
18.
Front Neurol ; 10: 1144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708865

RESUMO

Tuberous Sclerosis Complex (TSC) is a rare autosomal-dominant disorder caused by mutations in the TSC1 or TSC2 genes. Patients with TSC may suffer from a wide range of clinical manifestations; however, the burden of TSC and its impact on healthcare resources needed for its management remain unknown. Besides, the use of resources might vary across countries depending on the country-specific clinical practice. The aim of this paper is to describe the use of TSC-related resources and treatment patterns within the TOSCA registry. A total of 2,214 patients with TSC from 31 countries were enrolled and had a follow-up of up to 5 years. A search was conducted to identify the variables containing both medical and non-medical resource use information within TOSCA. This search was performed both at the level of the core project as well as at the level of the research projects on epilepsy, subependymal giant cell astrocytoma (SEGA), lymphangioleiomyomatosis (LAM), and renal angiomyolipoma (rAML) taking into account the timepoints of the study, age groups, and countries. Data from the quality of life (QoL) research project were analyzed by type of visit and age at enrollment. Treatments varied greatly depending on the clinical manifestation, timepoint in the study, and age groups. GAB Aergics were the most prescribed drugs for epilepsy, and mTOR inhibitors are dramatically replacing surgery in patients with SEGA, despite current recommendations proposing both treatment options. mTOR inhibitors are also becoming common treatments in rAML and LAM patients. Forty-two out of the 143 patients (29.4%) who participated in the QoL research project reported inpatient stays over the last year. Data from non-medical resource use showed the critical impact of TSC on job status and capacity. Disability allowances were more common in children than adults (51.1% vs 38.2%). Psychological counseling, social services and social worker services were needed by <15% of the patients, regardless of age. The long-term nature, together with the variability in its clinical manifestations, makes TSC a complex and resource-demanding disease. The present study shows a comprehensive picture of the resource use implications of TSC.

19.
Proc Natl Acad Sci U S A ; 116(48): 24150-24156, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31712446

RESUMO

Changing from summer-brown to winter-white pelage or plumage is a crucial adaptation to seasonal snow in more than 20 mammal and bird species. Many of these species maintain nonwhite winter morphs, locally adapted to less snowy conditions, which may have evolved independently. Mountain hares (Lepus timidus) from Fennoscandia were introduced into the Faroe Islands in 1855. While they were initially winter-white, within ∼65 y all Faroese hares became winter-gray, a morph that occurs in the source population at low frequency. The documented population history makes this a valuable model for understanding the genetic basis and evolution of the seasonal trait polymorphism. Through whole-genome scans of differentiation and single-nucleotide polymorphism (SNP) genotyping, we associated winter coat color polymorphism to the genomic region of the pigmentation gene Agouti, previously linked to introgression-driven winter coat color variation in the snowshoe hare (Lepus americanus). Lower Agouti expression in the skin of winter-gray individuals during the autumn molt suggests that regulatory changes may underlie the color polymorphism. Variation in the associated genomic region shows signatures of a selective sweep in the Faroese population, suggesting that positive selection drove the fixation of the variant after the introduction. Whole-genome analyses of several hare species revealed that the winter-gray variant originated through introgression from a noncolor changing species, in keeping with the history of ancient hybridization between the species. Our findings show the recurrent role of introgression in generating winter coat color variation by repeatedly recruiting the regulatory region of Agouti to modulate seasonal coat color change.

20.
Medicina (Kaunas) ; 55(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615098

RESUMO

Background and Objectives: Recent studies have shown the existence of a positive relationship between physical exercise, symptomatic improvement, and reduction of damage caused by comorbidities associated with autistic spectrum disorder (ASD) in children, adolescents, and adults. The aim of this systematic review with meta-analysis (SRM) was to estimate the effects of physical exercise (PE) on the stereotyped behaviors of children with a diagnosis of ASD in intervention studies. Materials and Methods: The design followed the PRISMA guidelines and the TREND statement to assess the quality of information in each study. Nine non-randomized intervention trial studies with low, moderate, and vigorous physical exercise, with a duration varying from 8 to 48 weeks and a frequency of 3 times a week, were included in the SRM. The dependent variable episodes of stereotypical behaviors was analyzed in all studies and assessed as the number of episodes demonstrated by the child in pre- versus post-exercise intervention conditions. Results: The eight studies included a total 129 children (115 males and 14 females) with an average age of 8.93 ± 1.69 years. Children with ASD showed a reduction of 1.1 in the number of occurrences of stereotypical behaviors after intervention with physical exercise. Conclusion: Evidence was found to support physical exercise as an effective tool in reducing the number of episodes of stereotypical behaviors in children diagnosed with ASD.

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