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In the context of “TO CHAIR” project, this work aims to improve the accuracy of short-term forecasts of maximum air temperature obtained from the https://weatherstack.com/website. The proposed methodology is based on a state-space representation that incorporates the latent process, the state, which is estimated recursively using the Kalman filter. The proposed model linearly and stochastically relates the forecasts from the website (as a covariate) to the observations of the maximum temperature recorded at the study site. The specification of the state-space model is performed using the maximum likelihood method under the assumption of normality of errors, where empirical confidence intervals are presented. In addition, this work also presents a treatment of outliers based on the ratios between the observed maximum temperature and the website forecasts. published

Achyrocline satureioides (Lam.) DC is a plant in the Asteraceae family that is commonly known as macela or marcela. It has antidiarrheal, antispasmodic, analgesic, anti-inflammatory and antimicrobial properties. The species Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are of great clinical importance, thus more evidence on the discovery of new compounds from plant species is required. The aim of this study was to evaluate the phytochemical profile and in vitro antimicrobial potential of essential oils from A. satureioides. A Minimal Inhibitory Concentration (MIC) test was performed using microdilution, and the chemical composition of the essential oil was analyzed using Gas Chromatography coupled to Mass spectrometry (GC / MS). Using the GC / MS analysis, we identified alpha-pinene and (E)-cariophilene as major phytoconstituents. We observed synergisms when the essential oil was combined with gentamicin and ampicillin against the S. aureus strain, as well as against E. coli when combined with gentamicin and norfloxacin. The results were promising, but further research is needed to assess the toxicity of A. satureioides oil and its potential for therapeutic use in humans.

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activation which is an important driver of sterile inflammation, however, the underlying molecular basis remains unclear. This work aimed to investigate the role of ER-mitochondria communication during ER stress-induced NLRP3 inflammasome activation in both peripheral and central innate immune systems, by using THP-1 human monocytes and BV2 microglia cells, respectively, as in vitro models. Markers of ER stress, mitochondrial dynamics and mass, as well as NLRP3 inflammasome activation were evaluated by Western Blot, IL-1β secretion was measured by ELISA, and ER-mitochondria contacts were quantified by transmission electron microscopy. Mitochondrial Ca

Despite clear technical superiority of genome sequencing (GS) over other diagnostic methods such as exome sequencing (ES), few studies are available regarding the advantages of its clinical application. We analyzed 1007 consecutive index cases for whom GS was performed in a diagnostic setting over a 2-year period. We reported pathogenic and likely pathogenic (P/LP) variants that explain the patients’ phenotype in 212 of the 1007 cases (21.1%). In 245 additional cases (24.3%), a variant of unknown significance (VUS) related to the phenotype was reported. We especially investigated patients which had had ES with no genetic diagnosis (n = 358). For this group, GS diagnostic yield was 14.5% (52 patients with P/LP out of 358). GS should be especially indicated for ES-negative cases since up to 29.6% of them could benefit from GS testing (14.5% with P/LP, n = 52 and 15.1% with VUS, n = 54). Genetic diagnoses in most of the ES-negative/GS-positive cases were determined by technical superiority of GS, i.e., access to noncoding regions and more uniform coverage. Importantly, we reported 79 noncoding variants, of which, 41 variants were classified as P/LP. Interpretation of noncoding variants remains challenging, and in many cases, complementary methods based on direct enzyme assessment, biomarker testing and RNA analysis are needed for variant classification and diagnosis. We present the largest cohort of patients with GS performed in a clinical setting to date. The results of this study should direct the decision for GS as standard second-line, or even first-line stand-alone test.

Background Falls and violence against older people might represent a joint public health problem, as both may result in injury, fear, social isolation, sedentary behavior and dependence or even death. The ESACA project “Aging safely in Alentejo - Understanding for action” was designed to promote the healthy aging of older people in Alentejo by preventing the occurrence of falls and violence. This study aimed to report the ESACA protocol and the preliminary outcomes. Methods The ESACA study has a twofold design as a cross-sectional study that included retrospective and prospective surveys. The participants were 508 community-dwelling older people. Assessments included falls, the risk of violence against older people, sociodemographic characteristics, health-related measurements, fear of falling, anthropometric measures and body composition, functional physical fitness, physical activity, and environmental hazards. Results Among the participants, 43% were fallers, 21% were recurrent fallers, and 22% were victims of one or more kinds of violence (psychological: 17.1%, physical: 5.6%, and patrimonial: 3.0%). Moreover, the cumulative results suggested high risk on several risk factors for falling (7 factors: 0.6% to 2 factors: 17.4%) and of violence (26.7%). Conclusions In the ESACA project, a wide range of potential influencing factors on falls and violence risk factors were measured, and comprehensive quality control measures were applied. Overall, the results suggest that for falls and violence prevention strategies to be effective, it is essential to evaluate, diagnose, and inform all stakeholders in a directed and useful way. Moreover, we believe that our project outcomes may help change mindsets and behaviors by involving people in active aging and well-being programs that promote exercise and avoid isolation.

Background Multimodal forms of exercise can influence several physical and mental factors important for successful aging. In the present study, we introduce a new type of multimodal intervention, combining movement (creative dance) with traditional singing. This study aims to compare physical fitness, functional physical independence, depressive symptoms, general cognitive status, and daytime sleepiness among older adults participating in multimodal exercise, those participating in traditional physical exercise, and those not actively engaged in physical exercise. Methods This cross-sectional study included 112 people aged ≥ 65 years (75.3 ± 0.7 years) living independently in the community, divided into 3 groups: multimodal exercise (n = 34), traditional exercise (n = 41), and no physical exercise (n = 37). Results The multimodal exercise group showed greater flexibility of the lower limbs and upper limbs/shoulders and better general cognitive status than the traditional exercise group (p p Conclusions The results suggest that the two types of programs studied may have different impacts on some of the variables investigated and support the design of future experimental studies that include interventions based on the combination of creative dance and traditional Portuguese singing.

Background Fall risk assessment and determination of older adults’ individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults. Methods Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics. Results The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32–33, high risk: score 30–31, and very high: score 44 kg, moderate risk: 42–44 kg, high risk: 39–41 kg, and very high: 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300–2800 Met-min/wk., high risk: 1900–2300 Met-min/wk., and very high: 5 h/day); health conditions (low risk: n n = 3, high risk: n = 4–5, and very high: n > 5); and environmental hazards (low risk: n n = 5, high risk: n = 6–8, and very high: n > 8). Conclusions Assessment of community-dwelling older adults’ fall risk should focus on the above outcomes to establish individual older adults’ fall risk profiles. Moreover, the design of fall prevention interventions should manage a person’s identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification.

Chestnut is an important crop in Portugal, representing an important source of revenue for mountain regions in this country. However, it has been strongly affected by the chestnut blight, a severe disease with negative consequences to fruit production, since there is still no definitive solution to this problem. Silicon is considered a nutrient for agricultural crops by conferring resistance to plants under biotic stress conditions through the combination of a physical and chemical defense system to fight against pathological fungi which attack leaves, roots and stems. Based on these factors, this study evaluates the influence of SiK® on chestnut plants infected with Cryphonectria parasitica. Three concentrations were studied: 5 mM, 7.5 mM and 10 mM SiK®. Results showed that Si fertilization can reduce the disease severity and the mortality rate of chestnut plants. The supply of 7.5 and 10 mM SiK® on PDA petri plates resulted in a total capacity of suppression (100% PI) of C. parasitica mycelium growth as opposed to the control petri plates (PDA). These concentrations also increased the antioxidant enzyme activity, catalase (CAT) and superoxide dismutase (SOD) measured 60 days after the inoculation with the fungus. In addition, the SiK® application increased the total phenolic compounds and soluble proteins content, which occurred over time. Also, increasing concentrations of SiK® increased the tolerance of seedlings to C. parasitica. The present study indicates that Si fertilization may be used in the future as a control method against chestnut blight.

Background Vici syndrome is a severe inherited multisystem disease caused by mutations in the EPG5 gene. The diagnosis depends on the constellation of cardinal features of agenesis of the corpus callosum, cataracts, oculocutaneous hypopigmentation, cardiomyopathy, and a combined immunodeficiency followed by confirmation by genetic testing. We report an Egyptian infant with Vici syndrome carrying a homozygous splice site variant (c.1252+1G>T; NM_020964.2) in the EPG5 gene, detailed clinical description, outcome, and differential diagnosis of inherited hypopigmentation disorders associated with neurological manifestations. Case presentation The infant initially presented with oculocutaneous hypopigmentation, agenesis of the corpus callosum, and immunodeficiency. A few months later, a diagnosis of dilated cardiomyopathy was made. Family history revealed 2 deceased siblings phenotypically matching our index infant. He died at the age of 15 months with acute respiratory failure. Conclusion The accurate diagnosis of such rare diseases with genetic confirmation is vital for proper clinical decision-making, genetic counseling of the affected families, and future genotype-phenotype correlation studies.

We implemented a collaborative diagnostic program in Lahore (Pakistan) aiming to establish the genetic diagnosis, and to asses diagnostic yield and clinical impact in patients with suspected genetic diseases. Local physicians ascertained pediatric patients who had no previous access to genetic testing. More than 1586 genetic tests were performed in 1019 individuals (349 index cases, 670 relatives). Most frequently performed tests were exome/genome sequencing (ES/GS, 284/78 index cases) and specific gene panels (55 index cases). In 61.3% of the patients (n = 214) a genetic diagnosis was established based on pathogenic and likely pathogenic variants. Diagnostic yield was higher in consanguineous families (60.1 vs. 39.5%). In 27 patients, genetic diagnosis relied on additional biochemical testing, allowing rapid assessment of the functional effect of the variants. Remarkably, the genetic diagnosis had a direct impact on clinical management. Most relevant consequences were therapy related such as initiation of the appropriated treatment in a timely manner in 51.9% of the patients (n = 111). Finally, we report 12 candidate genes among 66 cases with no genetic diagnosis. Importantly, three of these genes were validated as ‘diagnostic’ genes given the strong evidence supporting causality derived from our data repository (CAP2-dilated cardiomyopathy, ITFG2-intellectual disability and USP53-liver cholestasis). The high diagnostic yield, clinical impact, and research findings demonstrate the utility of genomic testing, especially when used as first-line genetic test. For patients with suspected genetic diseases from resource-limited regions, ES can be considered as the test of choice to achieve genetic diagnosis.

Chronic lymphocytic leukaemia (CLL) mostly affects patients with comorbidities and limited therapeutic options. Obinutuzumab in combination with chlorambucil (GClb) is a new therapeutic option for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy. This combination delays disease progression but incurs additional costs; thus, an assessment of its value for money is relevant. To estimate the incremental cost-utility ratio of GClb in comparison with (i) rituximab in combination with chlorambucil (RClb), and (ii) chlorambucil alone (Clb) from the perspective of the Portuguese National Health Service (NHS). A Markov model was used to predict disease progression. Pre‐progression clinical data were based on the latest CLL11 trial data, and post‐progression clinical data were obtained from CLL5 trial data. Utility values are from Kosmas et al. (Leuk Lymphoma 56:1320–1326, 14). Only direct medical costs were included. The resource consumption was estimated by a panel of Portuguese experts, and the unit costs were obtained from official sources. A discount rate of 5% was applied to costs and consequences. GClb and RClb were associated with an increase of 1.06 and 0.39 quality-adjusted life-years (QALY) at an additional cost of €21,720 and €9836 when compared to Clb, respectively. The cost-utility ratio of GClb versus Clb was €20,397/QALY, while RClb was extendedly dominated. The use of GClb for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy incurs an incremental cost per QALY that is generally accepted in Portugal. Therefore, although there is some uncertainty, obinutuzumab is probably a cost-effective therapy in the Portuguese setting.

It is already known by the scientific and industrial communities that lignocellulosic substrates are, to a certain extent, inhibitors of the hydration reaction of cement. The extent to which and how they influence such reactions is still a matter of debate. Several techniques, such as calorimetry, i.e., the measurement of the heat evolved or obtaining temperature profiles during the hydration, the determination of extractive contents of lignocellulosic substrates and their relation with the characteristics of the hydration curves, or even testing of the mechanical properties of the wood-cement composites, have been used in previous research. This study complements past research using two techniques that have been used in the analysis of cement hydration but are not usually applied to lignocellulose-cement mixes, namely X-ray diffraction (XRD) and differential thermal analysis (DTA). The raw materials for this study were three lignocellulosic materials of Portuguese origin: cork (the bark of Quercus suber L.), blue gum (Eucalyptus globulus Labill.), and maritime pine (Pinus pinaster Ait); and Portland cement. The two techniques allowed tracking of the evolution of the main cement constituents during hydration. It was found that all the lignocellulosic substrates had detrimental effects on cement hydration. The blue gum exhibited the fastest hydration kinetics in the initial stage of reaction, but was then overtaken by cork, which at the end gave the highest hydration conversion amongst the three lignocellulosic substrates. Although pine caused the slowest initial hydration kinetics, with the passage of time its effect approached that of blue gum. At the end of the hydration period, specimens containing either species had similar quantities of hydration reaction products. The DTA and XRD results were consistent and are in good agreement with the temperature profiles and compatibility indexes reported in a previous work.

Data are presented on the effects that cork, blue gum, or maritime pine, all grown in Portugal, have on cement setting. These materials were mixed with cement either without any treatment or after being extracted previously with a range of solvents (ranging from nonpolar to very polar). Other experiments were carried out in which extractives or calcium chloride were added to the cement paste. All lignocellulosic substrates have detrimental effects on cement setting, which is mostly seen by a delay in attaining the maximum temperature in the process. However, the addition of calcium chloride was able to overcome this disadvantage. Extraction of the substrates with some polar extraction agents before addition to the cement paste only slightly improved compatibility, and the addition of water-based extractives to a cement paste affects the setting much less than the lignocellulosic material by itself. Several thermal compatibility indices, including a new index proposed in this article, were calculated from data taken from temperature profiles, and conclusions are presented on the performance of the setting systems, as compared with a neat cement paste. In addition, comments are expressed on the level of accuracy offered by the indices applied in this study, and how such accuracy can be checked or improved by matching them to the physical properties of the wood-cement composites.

This paper reviews the research reported mostly in the last 10 years in the most common journals on the wood-cement composites field. The focused topics include: the problem of the compatibility (or not) between cement and woods, what causes it, ways of overcoming the problem; methods for manufacture and the properties exhibited by common wood-composites; special techniques to accelerate the curing of cement and to improve the properties of wood-cement composites; manufacture of nonwood vegetable raw materials-cement composites; durability against weathering and fungi; and construction materials. A discussion on the state-of-the-art is also presented.