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There is limited information on rare spinocerebellar ataxia (SCA) variants, particularly in the Canadian population. This study aimed to describe the demographic and clinical features of uncommon SCA subtypes in Canada and compare them with international data.
Methods:
We conducted a case series and literature review of adult patients with rare SCA subtypes, including SCA5, SCA7, SCA12, SCA14, SCA15, SCA28, SCA34, SCA35 and SCA36. Data were collected from medical centers in Ontario, Alberta and Quebec between January 2000 and February 2021.
Results:
We analyzed 25 patients with rare SCA subtypes, with onset ages ranging from birth to 67 years. Infantile and juvenile-onset cases were observed in SCA5, SCA7, SCA14 and SCA34. Most patients presented with gait ataxia, with no significant differences across groups. Additional common features included saccadic abnormalities (22 of 25), dysarthria (19 of 25) and nystagmus (12 of 22, except in SCA7). Less common findings included dystonia (8 of 25), cognitive impairment (7 of 25), tremor (9 of 25) and parkinsonism (3 of 25).
Conclusion:
Our study highlights the heterogeneity of rare SCA subtypes in Canada. Ongoing longitudinal analysis will improve the understanding, management and screening of these disorders.
Visceral leishmaniasis (VL) is a tropical disease that can be fatal if acute and untreated. Diagnosis is difficult, the treatment is toxic and prophylactic vaccines do not exist. Leishmania parasites express hundreds of proteins and several of them are relevant for the host's immune system. In this context, in the present study, 10 specific T-cell epitopes from 5 parasite proteins, which were identified by antibodies in VL patients’ sera, were selected and used to construct a gene codifying the new chimeric protein called rCHI. The rCHI vaccine was developed and thoroughly evaluated for its potential effectiveness against Leishmania infantum infection. We used monophosphoryl lipid A (MPLA) and polymeric micelles (Mic) as adjuvant and/or delivery system. The results demonstrated that both rCHI/MPLA and rCHI/Mic significantly stimulate an antileishmanial Th1-type cellular response, with higher production of IFN-γ, TNF-α, IL-12 and nitrite in vaccinated animals, and this response was sustained after challenge. In addition, these mice significantly reduced the parasitism in internal organs and increased the production of IgG2a isotype antibodies. In vivo and in vitro toxicity showed that rCHI is safe for the mammalians, and the recombinant protein also induced in vitro lymphoproliferative response and production of Th1-type cytokines by human cells, which were collected from healthy subjects and treated VL patients. These data suggest rCHI plus MPLA or micelles could be considered as a vaccine candidate against VL.
Tropical insectivorous birds comprise a diverse group that has a distinct response to habitat degradation. However, knowledge on birds’ ecological functions and their large-scale functional responses to human impacts across various habitats is scarce. We sampled 22 1-km-radius buffer landscapes within the Cantareira-Mantiqueira region (south-east Brazil), including native forests, pastures and marshes, to assess how landscape and habitat characteristics might affect insectivorous birds within the Brazilian Atlantic Forest. We studied whether bird species and functional diversity might respond to habitat turnover and nestedness and to native forest cover using generalized linear mixed models. We found negative effects of increased native forest cover on functional diversity indices. Bird communities in pastures show more nestedness, whereas marsh areas exhibit higher turnover. Forest areas receive a balanced contribution from both nestedness and turnover. These results are attributable to the predominantly secondary growth and early successional stages of the native forest fragments in the region, emphasizing the connection between landscape characteristics, habitat types and bird functional diversity in the Brazilian Atlantic Forest.
The NIH National Center for Advancing Translational Science (NCATS) was established to support translational research that spans the entire TS Continuum, with the goal of bridging the gap between preclinical biomedical research and real-world applications to advance treatments to patients more quickly. In 2018, the Translational Science Training (TST) TL1 Program at the University of Texas Health Science Center at San Antonio implemented new strategies to better include and encourage research more broadly across the TS Continuum, including the addition of postdoctoral scientists and a clinically trained Program Co-Director, expansion of team science and community engagement programming, and targeted trainee recruitment from schools of nursing, dentistry, and allied health, in addition to medicine. The objective of this bibliometric analysis was to determine if the program exhibited a more diverse mix of T-types after the adjustments made in 2018. The TST/TL1 Program experienced a shift in T-type, from mostly T0 (preclinical) to more T3/T4 (clinical implementation/public health) research, after new strategies were implemented. This supports the conclusion that strategic programmatic adjustments by an NCATS-funded predoctoral training program resulted in outcomes that better align with NCATS priorities to develop Trainees who contribute across the entire TS Continuum.
Background: Fluctuation-related pain (worse in OFF periods) is a frequent and disabling symptom in Parkinson’s disease (PD). As evidence-based treatments to treat pain in PD are limited, exploring alternatives to treat it are imperative. Apomorphine is the only antiparkinsonian agent compatible with levodopa in improving PD motor symptoms and is usually well tolerated. We explored the effects of apomorphine in PD fluctuation-related pain. Methods: Small pilot double-blind, placebo controlled, randomized crossover study evaluating the safety and efficacy of subcutaneous apomorphine vs. placebo on fluctuation-related PD pain including participants experiencing pain during OFF periods. Primary outcomes: changes in a Visual Analogue Scale for pain and MDS-UPRDS III from baseline to 30 and 60 minutes after injections (two doses, separated by 60 min) and adverse events. Domperidone was used as premedication to avoid nausea/vomiting. Results: 16 patients were screened and 11 completed the study. All participants tolerated both treatments without significant side effects. Efficacy results remain blinded until the end of February 2023 and will be shown at the conference. Conclusions: Apomorphine, recently approved by Health Canada as an adjunctive therapy in PD patients and experiencing “off” periods, has shown to be safe when used to treat fluctuation-related PD pain. Efficacy outcomes will be soon available.
Background: Pain is a frequent symptom in Parkinson’s disease (PD), and the therapeutic alternatives are scarce. The goal of this trial was to assess the effects of botulinum toxin type A (BTXA) in the treatment of foot dystonia in PD. Methods: Randomized placebo-controlled trial (RCT) (double-blind parallel-group study) evaluating the safety and efficacy of BTXA for PD-related painful foot dystonia using 100 units of BTXA/placebo, followed by an open-label phase. The primary outcome was a change in pain on the King’s Parkinson’s disease Pain scale and on a visual analogue scale at 6, 12 and 24 weeks. Secondary outcomes included the percentage of responders, clinical global impression, MDS-UPDRS, PDQ-39 scores, and adverse events. Results: 40 subjects were screened and 33 were enrolled. The RCT blind will be opened in March 2023 after the final study visit and data will be available for presentation at the June 2023 conference. The current open-label phase has revealed a preliminary that the toxin is safe and effective in reducing pain in PD-related foot dystonia with 84% of participants noticing a significant benefit. Conclusions: According to our preliminary data, targeted BTXA injections are a safe and effective treatment in patients with foot dystonia and PD.
Background: People with parkinsonian syndromes (PPS) in advanced stages deal with a wide range of highly impactful motor and non-motor problems, including dementia, hallucinations, falls, and dysautonomia. Care planning becomes difficult and unpredictable. In addition, while healthcare providers focus on reducing symptom burden, PPS and carepartners deal with difficult emotions such as demoralization and grief. At those stages, multidisciplinary care becomes imperative. In October 2022 we launched Advanced Care Team for Parkinson’s (ACT-PD), a clinical research program whose goals include advanced care planning, symptoms management and emotional support. Methods: Our primary outcomes are changes in quality of life (QoL-AD), carepartner burden (ZBI-12) and patient satisfaction. The team involves neurology, palliative nursing, social-work, psychology, and spiritual care. Every three months, participants meet the team in person or virtually. In two hours, they address tailored concerns, complemented with phone calls as required. Accordingly, participants complete assessments. Results: In its first 4 months, ACT-PD included 40 PPS and 40 carepartners. Preliminary results show that the first visit with ACT-PD resulted in a 30% reduction in carepartner burden and 28% of improvement in patients’ QoL. Conclusions: Even in early phases, this novel patient and carepartner-centered approach improves QoL and reduces carepartner burden in PPS in advanced disease stages.
Background: Pain is one of the most bothersome symptoms reported in Parkinson’s disease (PD), yet its underlying pathophysiological mechanisms are not well understood. Its prevalence and effects on quality of life in patients with monogenic forms of PD have not been systematically explored. Methods: Comprehensive literature review exploring the association between monogenic forms of PD (SNCA, PRKN, PINK1, DJ1, and LRRK2) and pain. We included pain in ATP13A2, VPS35, and GBA1 mutation carriers. After initial screening, sixty-five relevant articles were identified. Studies’ design, sample sizes, and pain outcome measures were highly heterogeneous. Results: Our review suggests that patients with some PD monogenic causes show a higher prevalence of specific pain subtypes. While painful foot dystonia is more frequently reported in SNCA and PRKN carriers, the last ones also describe frequent lower back pain mostly. Pain in general is most commonly reported in PINK1 mutation carriers followed by patients with LRRK2 mutations. Pain as an initial symptom and severe symptom is well described in GBA1-PD patients. There is limited and insufficient evidence to report on pain and ATP13A2, DJ1, and VPS35 mutations. Conclusions: Linking genetic profiles to pain outcomes may have a meaningful clinical impact, facilitating individualized treatment for pain in PD.
The home-field advantage (HFA) hypothesis establishes that plant litter decomposes faster at ‘home’ sites than in ‘away’ sites due to more specialized decomposers acting at home sites. This hypothesis has predominantly been tested through ‘yes or no’ transplanting experiments, where the litter decomposition of a focal species is quantified near and away from their conspecifics. Herein, we evaluated the occurrence and magnitude of home-field effects on the leaf litter decomposition of Myrcia ramuliflora (O.Berg) N. Silveira (Myrtaceae) along a natural gradient of conspecific litterfall input and also if home-field effects are affected by litter and soil traits. Litter decomposition of M. ramuliflora was assessed through litterbags placed in 39 plots in a tropical heath vegetation over a period of 12 months. We also characterized abiotic factors, litter layer traits, and litter diversity. Our results indicated the occurrence of positive (i.e. Home-field advantage) and negative (i.e. Home-field disadvantage) effects in more than half of the plots. Positive and negative effects occurred in a similar frequency and magnitude. Among all predictors tested, only the community weighted mean C/N ratio of the litterfall input was associated with home-field effects. Our results reinforce the lack of generality for home-field effects found in the literature and thus challenge the understanding of litter-decomposer interaction in tropical ecosystems.
Bemisia tabaci is a complex of species, which is considered the most common and important pest of a wide range of crops belonging to many different botanical families. In Argentina, this species is recognized as a vector of geminiviruses, and Middle East-Asia Minor 1, Mediterranean, New World and New World 2 have been found to coexist in the same area. Landscape elements, like habitat patch area and isolation, define the habitat configuration and have a direct effect on insect populations between and within host patches. In this paper, we analyse the effect of potato patch configuration on the distribution and abundance of B. tabaci. Potato patches were identified using Landsat TM5 and TM7 images, and a supervised classification was performed to quantify the spatial distribution of the patches in the whole study area. Potato patch metrics were estimated using Fragstats 4.4. Generalized linear mixed models were employed to analyse the relationship between whiteflies and landscape configuration, through a multimodel inference approach, finding that B. tabaci abundance and landscape metrics were very variable. After a multimodel selection process, we found that perimeter-to-area ratio and Euclidean distance between patches were the variables that best explained whitefly abundance in potato patches. Implications of these findings are discussed.
Overnutrition or undernutrition during all or part of the reproductive cycle predisposes sows to metabolic consequences and poor reproductive health which contributes to a decrease in sow longevity and an increase in perinatal mortality. This represents not only an economic problem for the pig industry but also results in poor animal welfare. To maximise profitability and increase sustainability in pig production, it is pivotal to provide researchers and practitioners with synthesised information about the repercussions of maternal obesity or malnutrition on reproductive health and perinatal outcomes, and to pinpoint currently available nutritional managements to keep sows’ body condition in an optimal range. Thus, the present review summarises recent work on the consequences of maternal malnutrition and highlights new findings.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Rayleigh–Bénard convection (RBC) and Taylor–Couette flow (TCF) are two paradigmatic fluid dynamical systems frequently discussed together because of their many similarities despite their different geometries and forcing. Often these analogies require approximations, but in the limit of large radii where TCF becomes rotating plane Couette flow (RPC) exact relations can be established. When the flows are restricted to two spatial independent variables, there is an exact specification that maps the three velocity components in RPC to the two velocity components and one temperature field in RBC. Using this, we deduce several relations between both flows: (i) heat and angular momentum transport differ by $(1-R_{\Omega })$, explaining why angular momentum transport is not symmetric around $R_{\Omega }=1/2$ even though the relation between $Ra$, the Rayleigh number, and $R_{\Omega }$, a non-dimensional measure of the rotation, has this symmetry. This relationship leads to a predicted value of $R_{\Omega }$ that maximizes the angular momentum transport that agrees remarkably well with existing numerical simulations of the full three-dimensional system. (ii) One variable in both flows satisfies a maximum principle, i.e. the fields’ extrema occur at the walls. Accordingly, backflow events in shear flow cannot occur in this quasi two-dimensional setting. (iii) For free-slip boundary conditions on the axial and radial velocity components, previous rigorous analysis for RBC implies that the azimuthal momentum transport in RPC is bounded from above by $Re_S^{5/6}$, where $Re_S$ is the shear Reynolds number, with a scaling exponent smaller than the anticipated $Re_S^1$.
Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non–treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values.
Methods
TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB’s Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05.
Results
We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC.
Conclusion
Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.
Near 20% of the Portuguese population is aged 65 years or above, a value similar to most developed countries. This older adult population also suffers from obesity and obesity-related pathologies. The environment encompasses a set of obesity determinants and knowing the associations between the environment and obesity may help health professionals and caregivers to provide for the older adults.
In this study, we aimed to relate anthropometric measures with socio-demographic data in older adults.
This is a cross-sectional study using data from the Pronutrisenior project, collected in Vila Nova de Gaia, Portugal. The sample consists of 456 older adults, aged 65 to 92 years without cognitive impairment. The sample consisted of older adults living at their homes. Socio-demographic, clinical, geographical, and anthropometric data was collected. The statistical analysis used IBM-SPSS-22.0 and consisted on descriptive statistics, Pearson correlations and UniANOVA. Significantly results (p < 0.05) are reported.
These older adults were mostly females (54.2%) with a mean age of 73.8 years (sd = 6.3), mean body mass index (BMI) of 29.1kg/m2 (sd = 4.8), mean waist-to-height ratio (WHtR) of 0.623 (sd = 0.073) and mean percentage of body fat mass (%BFM) of 40.7% (sd = 8.9%) for females and 30.2% (sd = 8.5%) for males. BMI, WHtR and %BFM were positively correlated. In this sample of older adults, higher values of these measures were associated to being female, younger, less educated; to having articular pains and respiratory problems, and not having insomnia, hypertension, chewing problems nor hearing problems; to drink more liquids but not consuming dairy products daily; to not take nutritional supplements but to take more medicines; to be without somebody to talk to and to be more dependent; and to live in a house without stairs to climb and to live near other older adults, and in a more urbanized area with streets with steeper slopes.
In this sample of older adults, obesity is related with health characteristics and those are related with socio-demographic and geographical characteristics of the area of residence. Besides the identification of risk factors for the older adult population, this information may help designing health care policies that takes in consideration the physical and geographical characteristics of the neighbourhood of the area of residence of the older adults.
Malnutrition is a serious health problem among older adults. The Mini Nutritional Assessment (MNA) is the most used tool to assess malnutrition among older adults. It was proposed that the Screening section could be used as a short form of the MNA (MNA-SF), but the study of the two forms show a wide range of agreement (71.8 to 93.3% and Cohen's kappa from 0.52 to 0.78). Nevertheless, most of the studies recommend the use of the MNA-SF, but in some this conclusion is not completely congruent with the results. The aims of this work were to study the agreement between the nutritional status classification using the MNA-SF and the MNA-FF among Portuguese older adults living in the community, to compare the scores in each question of the MNA-FF between participants correctly or incorrectly classified using the MNA-SF, and to develop a more sensible version of the MNA-SF. The current study is part of the PRONUTRISENIOR project. Data from 456 older adults (54.2% females) aged 65 to 92 years (mean = 73; SD = 6) living in the community (Vila Nova de Gaia, Portugal) were analyzed. The agreement between the two classifications is 82.7%, but Cohen's k shows a weak agreement (weighted k = 0.497; p < 0,001). MNA-SF showed a very low sensitivity (42.6%) detecting participants malnourished or at risk of malnutrition. Participants classified as normal using the MNA-SF despite at risk using the MNA-SF presented lower scores in two items from the Assessment section: number of full meals eaten daily and amount of fluid consumed per day. These two items were included in MNA-SF to obtain an extended short-version (MNA-SF8), which presented a sensitivity of 91.8% (and a specificity of 79.9%). The areas under the ROC curves were 0.858 and 0.929, respectively for MNA-SF and MNA-SF8. The addition of two items to the MNA-SF provides a more sensible tool to detect risk of malnutrition among elderly. These findings suggest that, among the studied population, general eating-related questions regarding (full meals and fluid intake) are relevant to assess malnutrition. Similar studies should be carried out among other populations in order to verify the possibility of their generalization. [The PRONUTRISENIOR project was financed by Iceland, Liechtenstein and Norway through the EEA Grants (PT06 – Public Health Initiatives, reference 81NU5).]
According to the World Health Organization obesity it's the result of an abnormal or excessive body fat accumulation, which presents a high risk for the health. Bariatric surgery appears as an alternative to the conventional treatment for the morbid obese individuals. However, this type of intervention causes changes in the anatomy and physiology of the gastrointestinal tract, which may lead to the development of nutritional deficiencies in patients, in particular anemia.
Aim:
To evaluate micronutrient deficiencies in patients submitted to bariatric surgery in preoperative and postoperative periods, in particular iron, ferritin, and B12 vitamin.
Methods:
In this longitudinal study, we evaluated, retrospectively and prospectively, patients who attended the nutrition appointment at a central hospital. We completed a preexisting database containing anthropometric and biochemical data, adding biochemical data, at various periods: pre at 6th, 12th, 18th, 24th, 30th and 36th months post-surgery.
Results:
from the 121 patients submitted to bariatric surgery, 79,3% were female. The prevalence or iron deficiency reached 15%, ferritin deficiency reached almost 10% and B12 vitamin deficiency reached 18%. Furthermore there were deficiencies in other nutrients, e.g., vitamin D, magnesium and zinc. There was more than 85% adhesion to take the multivitamin supplementation and frequent use of specific supplementation.
Conclusion:
The prevalence of nutritional deficiencies is high, with a tendency to persist over time even with use of multivitamin supplementation, leading to the need for complementary supplementation, in particular to prevent the risk of anemia. Hence, periodic and long term monitoring is fundamental.