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Abstract Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.

Abstract Coevolutionary antagonism generates relentless selection that can favour genetic exchange, including transfer of antibiotic synthesis and resistance genes among bacteria, and sexual recombination of disease resistance alleles in eukaryotes. We report an unusual link between biological conflict and DNA transfer in bdelloid rotifers, microscopic animals whose genomes show elevated levels of horizontal gene transfer from non-metazoan taxa. When rotifers were challenged with a fungal pathogen, horizontally acquired genes were over twice as likely to be upregulated as other genes — a stronger enrichment than observed for abiotic stressors. Among hundreds of upregulated genes, the most markedly overrepresented were clusters resembling bacterial polyketide and nonribosomal peptide synthetases that produce antibiotics. Upregulation of these clusters in a pathogen-resistant rotifer species was nearly ten times stronger than in a susceptible species. By acquiring, domesticating, and expressing non-metazoan biosynthetic pathways, bdelloids may have evolved to resist natural enemies using antimicrobial mechanisms absent from other animals.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Abstract Background To our knowledge, only one study has examined the association between glucose variability (GV) and mortality in the elderly population with diabetes. GV was assessed by HbA1c, and a J-shaped curve was observed in the relationship between HbA1c thresholds and mortality. No study of GV was conducted during the COVID-19 pandemic and its lockdown. This study aims to evaluate whether GV is an independent predictor of all-cause mortality in patients aged 75 years or older with and without COVID-19 who were followed during the first year of the COVID-19 pandemic and its lockdown measures. Methods This was a retrospective cohort study of 407,492 patients from the AGED-MADRID dataset aged 83.5 (SD 5.8) years; 63.2% were women, and 29.3% had diabetes. GV was measured by the coefficient of variation of fasting plasma glucose (CV-FPG) over 6 years of follow-up (2015–2020). The outcome measure was all-cause mortality in 2020. Four models of logistic regression were performed, from simple (age, sex) to fully adjusted, to assess the effect of CV-FPG on all-cause mortality. Results During follow-up, 34,925 patients died (14,999 women and 19,926 men), with an all-cause mortality rate of 822.3 per 10,000 person-years (95% confidence interval (CI), 813.7 to 822.3) (739 per 10,000; 95% CI 728.7 to 739.0 in women and 967.1 per 10,000; 95% CI 951.7 to 967.2 in men). The highest quartile of CV-FPG was significantly more common in the deceased group (40.1% vs. 23.6%; p

Este texto indaga la posibilidad de definir un nuevo paradigma arquitectónico a partir de la detección de una serie de características comunes a una arquitectura contemporánea aparentemente preocupada por la construcción de lo mínimo y de lo esencial. El análisis de determinados proyectos y posiciones críticas clave acontecidas en los últimos años permite construir una posible genealogía proyectual con la que aproximarse a la definición de la idea de “nueva esencialidad”: una manera de operar que recupera el interés por el suelo y la flexibilidad de los soportes, que persigue la adaptabilidad a diferentes contextos y programas, que refuerza el orden y la organización a través de la sencillez geométrica de la planta y que se manifiesta con una nítida honestidad constructiva.

Abstract Background Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. Methods 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. Results Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p

Abstract Background Dairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest. Methods We analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses’ Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty. Results During follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty. Conclusions The results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk.

Objectives To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD).Design Prospective population-based cohort study.Setting 10 primary healthcare centres in the north of the city of Madrid (Spain).Participants A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose

Background: The positive influence of most types of exercise has been reported repeatedly, but what the most effective exercise approaches are for improving health-related quality of life (HRQoL) in people with cancer remains unknown. The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment. Methods: MEDLINE, SPORTDiscus, the Cochrane Library, Web of Science, and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer. Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires. We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains. Results: In total, 93 studies involving 7435 people with cancer were included. Network effect size estimates comparing exercise intervention vs. usual care were significant for combined exercise (0.35, 95% confidence interval (95%CI): 0.14–0.56) for HRQoL as measured by general questionnaires, and for combined (0.31, 95%CI: 0.13–0.48), mind–body exercise (0.54, 95%CI: 0.18–0.89), and walking (0.39, 95%CI: 0.04–0.74) for HRQoL as measured by cancer-specific questionnaires. Conclusion: Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment. The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.

IntroductionThe COVID-19 pandemic lockdowns (people confined to home, with movement restrictions) presented an external shock to livelihoods and food systems worldwide, most severely affecting vulnerable households in low-income countries. While evidence is available regarding how COVID-19 generally affected low-income countries, the specific dynamics of local food-system responses and sustainably-certified coffee farm households has not been examined, despite them being usually deemed to be more resilient to shocks. This research examines how local food systems in Honduras changed during lockdowns, how certified coffee households coped with the shock, especially food insecurity, and the potential role of coffee cooperatives in increasing households’ resilience under future shocks and stressors.MethodsWe applied a mixed-methods approach that combined a structured household survey with semi-structured qualitative interviews with 91 households, 6 cooperative representatives, and 18 food-system representatives.ResultsWe found that coffee-income-dependent households experienced greater food insecurity during lockdown than coffee households with diversified incomes. Before lockdown the local food system was highly dependent on external fresh food from outside the state. Food suppliers changed altered fresh-food procurement strategies, mostly to maintain fresh-food availability at the beginning of the pandemic. However, more than half the interviewed households lacked confidence regarding food security, amid rising food prices and local shortages. Certified coffee cooperatives supported their members by providing food assistance, cash transfers, and credit.DiscussionSome of these strategies are difficult to maintain where crises are recurrent and that may render households more vulnerable to future extreme events. Rather, coffee cooperatives could diversify and support their members in growing and marketing additional food crops. This could be a key approach for boosting local food security and strengthening the local food system.

Background. Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson’s disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge. Methods. We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques. Results. Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88. Conclusion. We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson’s disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life.

The present study evaluated the mechanical behavior of five designs of Morse taper (MT) connections with and without the application of loads. For this, the detorque of the fixing screw and the traction force required to disconnect the abutment from the implant were assessed. A total of 100 sets of implants/abutments (IAs) with MT-type connections were used, comprising five groups (n = 20/group): (1) Group Imp 11.5: IA sets with a cone angulation of 11.5°; (2) Group SIN 11.5: with a cone angulation of 11.5°; (3) Group SIN 16: with a cone angulation of 16°; (4) Group Neo 16: with a cone angulation of 16°; and (5) Group Str 15: with a cone angulation of 15°. All sets received the torque recommended by the manufacturer. After applying the torque, the counter torque of the fixing screws was measured in ten IA sets of each group without the application of cyclic loads (frequencies ≤ 2 Hz, 360,000 cycles, and force at 150 Ncm). The other ten sets of each group were subjected to cyclic loads, after which the detorque was measured. Afterwards, the force for disconnection between the implant and the abutment was measured by traction on all the samples. The untwisting of the abutment fixation screws showed a decrease in relation to the initial torque applied in all groups. In the unloaded samples, it was found to be −25.7% in Group 1, −30.4% in Group 2, −36.8% in Group 3, −29.6% in Group 4, and −25.7% in Group 5. After the applied loads, it was found to be −44% in Group 1, −43.5% in Group 2, −48.5% in Group 3, −47.2% in Group 4, and −49.8% in Group 5. The values for the IA sets were zero for SIN 16 (Group 3) and Neo16 (Group 4), both without and with loads. In the other three groups, without loads, the disconnection value was 56.3 ± 2.21 N (Group 1), 30.7 ± 2.00 N (Group 2), and 26.0 ± 2.52 N (Group 5). After applying loads, the values were 63.5 ± 3.06 N for Group 1, 34.2 ± 2.45 N in Group 2, and 23.1 ± 1.29 N in Group 5. It was concluded that in terms of the mechanical behavior of the five designs of MT IA sets, with and without the application of loads, the Imp 11.5, SIN 11.5, and Srt 15 groups showed better results compared to the SIN 16 and Neo 16 groups, showing that lower values of cone angulation increase the friction between the parts (IA), thus avoiding the need to maintain the torque of the fixing screw to maintain the union of the sets.

African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas.

Contemporary environmental awareness requires new architectural practices to reformulate the relationship between buildings and the ground. Among these, the way in which buildings land on the site emerges as a key architectural condition that must be reviewed, focusing on generating new systems of articulation, more sensitive and attentive to the specific conditions of the grounds. Drawing on the ecological perspectives put forth by authors like Bruno Latour in recent years, this article presents a critical analysis of the rooting systems developed by some of the most significant architectural practices today. This case study provides a catalogue of various sustainable topographical strategies that prioritize the conservation and nurturing of soil properties. The discussion of these strategies enables the synthesis of a series of design guidelines to foster new relationships of affinity with the land, positioning architecture not as an imposition on the territory but as a facilitator of its natural development.

Abstract Background This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes. Methods Peripheral blood samples from the CLEAR trial IS patients at ≤ 3 h, 5 h, and 24 h after stroke were compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome assessed using the modified Rankin Scale (mRS) and the NIH Stroke Scale (NIHSS). Results The expression of 467, 526, and 571 genes measured at ≤ 3, 5 and 24 h after IS, respectively, were associated with poor 90-day mRS outcome (mRS ≥ 3), while 49, 100 and 35 genes at ≤ 3, 5 and 24 h after IS were associated with good mRS 90-day outcome (mRS ≤ 2). Poor outcomes were associated with up-regulated genes or pathways such as IL-6, IL-7, IL-1, STAT3, S100A12, acute phase response, P38/MAPK, FGF, TGFA, MMP9, NF-kB, Toll-like receptor, iNOS, and PI3K/AKT. There were 94 probe sets shared for poor outcomes vs. controls at all three time-points that correlated with 90-day mRS; 13 probe sets were shared for good outcomes vs. controls at all three time-points; and 46 probe sets were shared for poor vs. good outcomes at all three time-points that correlated with 90-day mRS. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome for mRS and NIHSS. Poor outcome modules were enriched with up-regulated neutrophil genes and with down-regulated T cell, B cell and monocyte-specific genes; and good outcome modules were associated with erythroblasts and megakaryocytes. Finally, genes identified by genome-wide association studies (GWAS) to contain significant stroke risk loci or loci associated with stroke outcome including ATP2B, GRK5, SH3PXD2A, CENPQ, HOXC4, HDAC9, BNC2, PTPN11, PIK3CG, CDK6, and PDE4DIP were significantly differentially expressed as a function of stroke outcome in the current study. Conclusions This study suggests the immune response after stroke may impact functional outcomes and that some of the early post-stroke gene expression markers associated with outcome could be useful for predicting outcomes and could be targets for improving outcomes.

The peripheral immune system response to Intracerebral Hemorrhage (ICH) may differ with ICH in different brain locations. Thus, we investigated peripheral blood mRNA expression of Deep ICH, Lobar ICH, and vascular risk factor-matched control subjects (n = 59). Deep ICH subjects usually had hypertension. Some Lobar ICH subjects had cerebral amyloid angiopathy (CAA). Genes and gene networks in Deep ICH and Lobar ICH were compared to controls. We found 774 differentially expressed genes (DEGs) and 2 co-expressed gene modules associated with Deep ICH, and 441 DEGs and 5 modules associated with Lobar ICH. Pathway enrichment showed some common immune/inflammatory responses between locations including Autophagy, T Cell Receptor, Inflammasome, and Neuroinflammation Signaling. Th2, Interferon, GP6, and BEX2 Signaling were unique to Deep ICH. Necroptosis Signaling, Protein Ubiquitination, Amyloid Processing, and various RNA Processing terms were unique to Lobar ICH. Finding amyloid processing pathways in blood of Lobar ICH patients suggests peripheral immune cells may participate in processes leading to perivascular/vascular amyloid in CAA vessels and/or are involved in its removal. This study identifies distinct peripheral blood transcriptome architectures in Deep and Lobar ICH, emphasizes the need for considering location in ICH studies/clinical trials, and presents potential location-specific treatment targets.

Beyond 5G networks, and for short distance but high-speed communication systems, there is an incipient growing interest in visible light communications (VLC). Furthermore, it is an interesting alternative within the framework of the Internet of Things (IoT). However, there is a problem on the part of the receiver in these systems, motivated by the non-existence of photovoltaic elements used particularly for this purpose. Because of their simplicity and small investment, organic-type photodetectors have a high capacity for use in VLC systems. With a structure of polymers represented by an organic photodetector fabricated with poly (3-hexylthiophene) (P3HT) and a bulk heterojunction active layer of phenyl-C61-butyric acid methyl ester (PCBM) and commercial LEDs, we show our system in this paper. The main novelty of this work is in reception. With different upgrade using a new active layer or adding a focal lens or inserting a transimpedance amplifier, we have achieved improved performance results related to voltage and distance, with an increase of more than 40 %, and Bit Error Rate (BER) by modifying the active layer concentration with respect to results obtained in a former work. Also, we have tested the use of a transimpedance amplifier to obtain the best results in distances of 12 cm to 20 cm and a focal lens with the same objective of improving the BER in critical environments, where the Signal-to-Noise Ratio (SNR) is close to zero. To conclude, these modifications show that it is possible to increase the main parameters of our system to be useful in VLC systems.

BackgroundImproving health of children and adolescents is crucial for their overall development. Therefore, it is essential to explore factors that may influence their health at both the public health and school system levels.ObjectiveThis study compares physical fitness components and waist-height-to-ratio (WHtR) in adolescents according to school uniforms, namely the traditional uniform (i.e., shirt and school necktie in boys and skirt and blouse in girls) and the sports uniform (i.e., polo shirts or t-shirts and sport or short trousers). Additionally, it seeks to investigate potential differences in these measures based on sex and school type (i.e., public, subsidized, and private).MethodsThis cross-sectional study used data from the Chilean national learning outcome assessment system (SIMCE)–2014 and involved 8,030 adolescents. Cardiorespiratory fitness (CRF) and muscular fitness (MF) were measured. WHtR was assessed as a health cardiovascular indicator. Mixed models and ANCOVA were performed to compare uniform types, adjusting for multiple covariates. value of p and effect size (ES) was used to establish significant results.ResultsOverall, sports uniforms (SU) were linked to higher CRF (p

Processing incoming neural oscillatory signals in real-time and decoding from them relevant behavioral or pathological states is often required for adaptive Deep Brain Stimulation (aDBS) and other brain-computer interface (BCI) applications. Most current approaches rely on first extracting a set of predefined features, such as the power in canonical frequency bands or various time-domain features, and then training machine learning systems that use those predefined features as inputs and infer what the underlying brain state is at each given time point. However, whether this algorithmic approach is best suited to extract all available information contained within the neural waveforms remains an open question. Here, we aim to explore different algorithmic approaches in terms of their potential to yield improvements in decoding performance based on neural activity such as measured through local field potentials (LFPs) recordings or electroencephalography (EEG). In particular, we aim to explore the potential of end-to-end convolutional neural networks, and compare this approach with other machine learning methods that are based on extracting predefined feature sets. To this end, we implement and train a number of machine learning models, based either on manually constructed features or, in the case of deep learning-based models, on features directly learnt from the data. We benchmark these models on the task of identifying neural states using simulated data, which incorporates waveform features previously linked to physiological and pathological functions. We then assess the performance of these models in decoding movements based on local field potentials recorded from the motor thalamus of patients with essential tremor. Our findings, derived from both simulated and real patient data, suggest that end-to-end deep learning-based methods may surpass feature-based approaches, particularly when the relevant patterns within the waveform data are either unknown, difficult to quantify, or when there may be, from the point of view of the predefined feature extraction pipeline, unidentified features that could contribute to decoding performance. The methodologies proposed in this study might hold potential for application in adaptive deep brain stimulation (aDBS) and other brain-computer interface systems.

Abstract Background Red meat is a nutrient‐dense source of protein fundamental for older adults; however, red meat is also high in detrimental components, including saturated fat. It is unclear whether habitual red meat consumption is associated with risk of frailty. This study aimed to examine the prospective association between the consumption of total, unprocessed, and processed red meat and the risk of frailty in older adults. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Consumption of total, unprocessed, and processed red meat was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses, and unintentional weight loss ≥5%. The occurrence of frailty was assessed every four years from 1992 to 2014. Results During 22 years of follow‐up (median follow‐up 14 years), we identified 13 279 incident cases of frailty. Women with a higher intake of red meat showed an increased risk of frailty after adjustment for lifestyle factors, medication use, and dietary factors. The relative risk (95% confidence interval) for one serving/day increment in consumption was 1.13 (1.08, 1.18) for total red meat, 1.08 (1.02, 1.15) for unprocessed red meat, and 1.26 (1.15, 1.39) for processed red meat. When each component of the frailty syndrome was individually examined, each of them was positively associated with total red meat consumption, except for the weight loss criterion. Replacing one serving/day of unprocessed red meat with other protein sources was associated with significantly lower risk of frailty; the risk reduction estimates were 22% for fish and 14% for nuts, while for replacement of processed red meat, the percentages were 33% for fish, 26% for nuts, 13% for legumes, and 16% for low‐fat dairy. Conclusions Habitual consumption of unprocessed and processed red meat was associated with a higher risk of frailty. Replacement of red meat by other protein sources might reduce the risk of frailty. These findings are in line with dietary guidelines promoting diets that emphasize plant‐based sources of protein.

Eukaryotic DNA can be methylated as 5-methylcytosine and N6-methyladenine, but whether other forms of DNA methylation occur has been controversial. Here the authors show that a bacterial DNA methyltransferase was acquired >60 Mya in bdelloid rotifers that catalyzes N4-methylcytosine addition and is involved in suppression of transposon proliferation.

Abstract An advanced experimental and theoretical model to explain the correlation between the electronic and local structure of Eu $$^{2+}$$ 2 + in two different environments within a same compound, EuS, is presented. EuX monochalcogenides (X: O, S, Se, Te) exhibit anomalies in all their properties around 14 GPa with a semiconductor to metal transition. Although it is known that these changes are related to the $$4f^7 5d^0$$ 4 f 7 5 d 0 $$\rightarrow$$ → $$4f^6 5d^1$$ 4 f 6 5 d 1 electronic transition, no consistent model of the pressure-induced modifications of the electronic structure currently exists. We show, by optical and x-ray absorption spectroscopy, and by ab initio calculations up to 35 GPa, that the pressure evolution of the crystal field plays a major role in triggering the observed electronic transitions from semiconductor to the half-metal and finally to the metallic state.

Abstract Background The contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes. Methods A Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001–2003, and were followed-up to 2015 to ascertain incident type 2 diabetes. Results The HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and − 8.23 (95% CI, − 16.34, − 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes. Conclusions The HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.

Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici (Fol), causes losses in tomato production worldwide, with major impacts on Californian tomato processing. Single-gene resistance is the primary management tool, but its efficacy has been compromised following the emergence of two successive resistance-breaking races, which, in California, emerged within 12 years of resistance deployment. Fol race 3-resistant (F3) processing tomato cultivars (containing the I3 resistance gene) were deployed in the state starting in approximately 2009. The emergence of a new resistance-breaking race (which would be called race 4) is imminent, and early detection will be critical to delay the spread while new resistance is sought. The detection of Fol race 4 is challenged by the lack of validated, rapid, and accurate diagnostic tools. In evaluating in planta phenotyping methods, this study found that rapid seedling phenotyping is not reliable and generates false positives for nonpathogens. Longer (10 weeks) mature plant assays are the most reliable, but may not be sufficiently timely. As an additional challenge, based on field and greenhouse studies, Fol race 3 can cause symptoms in resistant F3 cultivars at frequencies greater (30%) than expected for off-types (

African swine fever virus (ASFV) currently represents the biggest threat to the porcine industry worldwide, with high economic impact and severe animal health and welfare concerns. Outbreaks have occurred in Europe and Asia since ASFV was reintroduced into the continent in 2007 and, in 2021, ASFV was detected in the Caribbean, raising alarm about the reemergence of the virus in the Americas. Given the lack of vaccines against ASFV, control of the virus relies on molecular surveillance, which can be delayed due to the need for sample shipment to specialized laboratories. Isothermal PCR techniques, such as LAMP, have become increasingly attractive as point-of-care diagnostic tools given the minimal material expense, equipment, and training required. The present study aimed to develop a LAMP assay for the detection of ASFV. Four LAMP primer sets were designed, based on a consensus sequence for the ASFV p72 gene, and were tested using a synthetic plasmid containing the cloned ASFV p72 target gene as a positive control. Two primer sets, were selected for further validation, given their very short time for amplification. Both primer sets showed thermal stability, amplifying the ASFV DNA at temperatures between 60-70°C and proved to have an analytical limit of detection as low as one ASFV-plasmid DNA copy/µL, using both fluorometric and colorimetric methods. The selected primers did not yield false positive or cross reactive results with other common swine pathogens, showing high specificity. Testing of DNA-spiked samples showed that LAMP amplification was not affected by the nature of the matrices, including oral fluids, tonsils, blood, or rectal swabs. The primer sets were able to detect the two more prevalent ASFV genotypes in the field. Taken together, the results show that ASFV-LAMP-BG2 and ASFV-LAMP-BG3 would be a useful tool for rapid, highly sensitive on-site diagnostic testing.

Abstract Identification of Parkinson’s disease subtypes may help understand underlying disease mechanisms and provide personalized management. Although clustering methods have been previously used for subtyping, they have reported generic subtypes of limited relevance in real life practice because patients do not always fit into a single category. The aim of this study was to identify new subtypes assuming that patients could be grouped differently according to certain sets of related symptoms. To this purpose, a novel model-based multi-partition clustering method was applied on data from an international, multi-center, cross-sectional study of 402 Parkinson’s disease patients. Both motor and non-motor symptoms were considered. As a result, eight sets of related symptoms were identified. Each of them provided a different way to group patients: impulse control issues, overall non-motor symptoms, presence of dyskinesias and pyschosis, fatigue, axial symptoms and motor fluctuations, autonomic dysfunction, depression, and excessive sweating. Each of these groups could be seen as a subtype of the disease. Significant differences between subtypes (P< 0.01) were found in sex, age, age of onset, disease duration, Hoehn & Yahr stage, and treatment. Independent confirmation of these results could have implications for the clinical management of Parkinson’s disease patients.

Abstract Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.

Abstract Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient’s risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

Background/Aims Peroral endoscopic myotomy (POEM) has been increasingly used for achalasia in Latin America, where Chagas disease is prevalent, and this makes POEM more challenging. The aim of this study was to determine the learning curve for POEM in Latin America. Method: Patients undergoing POEM in Latin America with a single operator were included from a prospective registry over 4 years. Non-linear regression and cumulative sum control chart (CUSUM) analyses were conducted for the learning curve. Results A total of 125 patients were included (52% male; mean age, 59 years), of which 80 had type II achalasia (64%), and 38 had Chagas disease (30%). The average pre-procedure and post-procedure Eckardt scores were 6.79 and 1.87, respectively. Technical success was achieved in 93.5% of patients, and clinical success was achieved in 88.8%. Adverse events occurred in 27 patients (22%) and included bleeding (4 patients), pneumothorax (4 patients), mucosal perforation (13 patients), mediastinitis (2 patients), and leakage (4 patients). The CUSUM chart showed a median procedure time of 97 min (range, 45-196 min), which was achieved at the 61st procedure. Procedure duration progressively decreased, with the last 10 procedures under 50 min approaching a plateau (p-value

SARS-CoV-2 is responsible for the COVID-19 pandemic, which has caused almost 570 million infections and over six million deaths worldwide. To help curb its spread, solutions using ultraviolet light (UV) for quick virus inactivation inside buildings without human intervention could be very useful to reduce chances of contagion. The UV dose must be sufficient to inactivate the virus considering the different materials in the room, but it should not be too high, not to degrade the environment. In the present study, we have analyzed the ability of a 254 nm wavelength UV-C lamp to inactivate dried samples of SARS-CoV-2 exposed at a distance of two meters, simulating a full-scale scenario. Our results showed that virus inactivation was extremely efficient in most tested materials, which included plastic, metal, wood, and textile, with a UV-C exposure of only 42 s (equivalent to 10 mJ/cm2). However, porous materials like medium density fibreboard, were hard to decontaminate, indicating that they should be avoided in hospital rooms and public places.

A large number of materials with different compositions and shapes have been proposed and studied for the purpose of bone tissue regeneration. Collagen-based materials have shown promising results for this application, with improved physicochemical properties. The aim of the present in vivo animal study was to evaluate and compare two commercially available collagen-based biomaterials for bone regeneration, with these being implanted in circumferential bone defects created in the calvarium of rabbits. Twenty rabbits received bilateral parietal osteotomies, performed with the aid of a 6.5 mm diameter trephine. Two groups were created: the BC group, where the defect was filled with a scaffold composed of 90% bovine bone particles and 10% porcine collagen, and the EG group, where the defect was filled with a scaffold composed of 75% hydroxyapatite particles of bovine origin and 25% bovine collagen. Ten animals were sacrificed at 30 days and another 10 at 45 days after implantation, and the samples were processed and histologically analyzed. In the evaluations of the samples at 30 days, no important differences were found in the results. However, in the samples at 45 days after surgery, the EG group showed better results than the BC group samples, mainly in terms of the amount of bone matrix formation ( P < 0.0001) and the volume in area measured in each sample, where the EG group had a value 65% higher than that in the BC group samples. Based on the results obtained, we conclude that the amount of collagen and the particle characteristics present in the composition of the scaffolds can directly influence the amount of neoformation and/or bone regeneration.

The Mediterranean diet (MedDiet) represents the traditional food consumption patterns of people living in countries bordering the Mediterranean Sea and is associated with a reduced incidence of obesity and type-2 diabetes mellitus (T2DM). The objective of this study was to examine differences in the composition of the oral microbiome in older adults with T2DM and/or high body mass index (BMI) and whether the microbiome was influenced by elements of a MedDiet. Using a nested case-control design individuals affected by T2DM were selected from the Seniors-ENRICA-2 cohort concurrently with non-diabetic controls. BMI was measured, a validated dietary history taken, and adherence to a Mediterranean diet calculated using the MEDAS (Mediterranean Diet Adherence Screener) index. Oral health status was assessed by questionnaire and unstimulated whole mouth saliva was collected, and salivary flow rate calculated. Richness and diversity of the salivary microbiome were reduced in participants with T2DM compared to those without diabetes. The bacterial community structure in saliva showed distinct “signatures” or “salivatypes,” characterized by predominance of particular bacterial genera. Salivatype 1 was more represented in subjects with T2DM, whilst those with obesity (BMI ≥ 30 kg/m2) had a predominance of salivatype 2, and control participants without T2DM or obesity had an increased presence of salivatype 3. There was an association of salivatype 1 with increased consumption of sugary snacks combined with reduced consumption of fish/shellfish and nuts. It can be concluded that the microbial community structure of saliva is altered in T2DM and obesity and is associated with altered consumption of particular food items. In order to further substantiate these observations a prospective study should be undertaken to assess the impact of diets aimed at modifying diabetic status and reducing weight.

Abstract Epidemiological studies have yielded conflicting results regarding climate and incident SARS-CoV-2 infection, and seasonality of infection rates is debated. Moreover, few studies have focused on COVD-19 deaths. We studied the association of average ambient temperature with subsequent COVID-19 mortality in the OECD countries and the individual United States (US), while accounting for other important meteorological and non-meteorological co-variates. The exposure of interest was average temperature and other weather conditions, measured at 25 days prior and 25 days after the first reported COVID-19 death was collected in the OECD countries and US states. The outcome of interest was cumulative COVID-19 mortality, assessed for each region at 25, 30, 35, and 40 days after the first reported death. Analyses were performed with negative binomial regression and adjusted for other weather conditions, particulate matter, sociodemographic factors, smoking, obesity, ICU beds, and social distancing. A 1 °C increase in ambient temperature was associated with 6% lower COVID-19 mortality at 30 days following the first reported death (multivariate-adjusted mortality rate ratio: 0.94, 95% CI 0.90, 0.99, p = 0.016). The results were robust for COVID-19 mortality at 25, 35 and 40 days after the first death, as well as other sensitivity analyses. The results provide consistent evidence across various models of an inverse association between higher average temperatures and subsequent COVID-19 mortality rates after accounting for other meteorological variables and predictors of SARS-CoV-2 infection or death. This suggests potentially decreased viral transmission in warmer regions and during the summer season.

Abstract Background Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain. Methods Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008–2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence). Results Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend

We developed a portable ultra-wideband radar system capable of reconfigurable operation in multiple frequency bands (separate or simultaneous) spanning from microwaves through millimeter waves. The instrument provides a compact solution for fine-resolution measurements of elevation changes and superficial snow/firn thickness from low-altitude, mid-sized airborne platforms. In this article, we provide an overview of the radar system design and its performance during laboratory testing. We demonstrate its application in aerial surveys of snow layer thickness at S/C bands, dual-band airborne altimetry at Ku-/Ka-bands, and present first-order comparisons with coincident airborne lidar data.

Background and Aimsrs964184 variant in the ZPR1 gene has been associated with blood lipids levels both in fasting and postprandial state and with the risk of myocardial infarction in high-risk cardiovascular patients. However, whether this association is modulated by diet has not been studied.ObjectiveTo investigate whether the type of diet (low-fat or Mediterranean diets) interacts with genetic variability at this loci to modulate fasting and postprandial lipids in coronary patients.Materials and MethodsThe genotype of the rs964184 polymorphism was determined in the Cordioprev Study population (NCT00924937). Fasting and Postprandial triglycerides were assessed before and after 3 years of dietary intervention with either a Mediterranean or a low-fat diet. Postprandial lipid assessment was done by a 4-h oral fat tolerance test (OFTT). Differences in triglycerides levels were identified using repeated-measures ANCOVA.ResultsFrom 523 patients (85% males, mean age 59 years) that completed the OFTT at baseline and after 3 years of intervention and had complete genotype information, 125 of them were carriers of the risk allele G. At the start of the study, these patients showed a higher fasting and postprandial triglycerides (TG) plasma levels. After 3 years of dietary intervention, G-carriers following a Mediterranean Diet maintained higher fasting and postprandial triglycerides, while those on the low-fat diet reduced their postprandial triglycerides to similar values to the population without the G-allele.ConclusionAfter 3 years of dietary intervention, the altered postprandial triglyceride response induced by genetic variability in the rs964184 polymorphism of the ZPR1 gene can be modulated by a low-fat diet, better than by a Mediterranean diet, in patients with coronary artery disease.

The main objective of the current study was to analyze how parents' sociodemographic characteristics, mode of commuting and physical activity (PA) act as indicators of active commuting to school (ACS) in their children and adolescents. A total of 684 paired parents (52.8% mothers) and their respective offspring (33.7% girls) were included. The participants self-reported their sociodemographic characteristics, mode of commuting, and PA. Logistic regression analyses were performed using a stepwise approach, including, as indicators, parental characteristics, mode of commuting and PA. The main outcome was child and adolescent ACS. The odds ratio (OR) and R2 of Nagelkerke were obtained for each step. Parental sociodemographic characteristics were greater indicators of child ACS than the parental mode of commuting and PA. In children, the greatest predictive variables of ACS explained 38% of the variance and were as follows: car availability (OR = 0.24), father's educational level (OR = 0.47), mother's educational level (OR = 1.95), mother's active commuting to work (OR = 4.52) and mother's salary/month (OR = 0.67). In adolescents, the greatest predictive variables of ACS explained 40% of the variance and were as follows: socioeconomic level (OR = 0.43) and father's active commuting (OR = 10.6). In conclusion, sociodemographic factors are better indicators of ACS than parents' physical activity and active commuting to work.

Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.

Ancient, asexual lineages are rare as a lack of recombination is usually an evolutionary dead end. Here, authors compare complete genomes of 11 individual bdelloid rotifers that suggest evidence of regular genetic exchange between individuals in a species that was previously thought to be asexual.

Several stakeholders have joined forces in recent years to facilitate consensus building on practices, indicators and standards that might serve to increase accountability and improve microfinance social performance. As a result, several sets of social standards have been developed to provide social performance assessment with a similar level of consistency and acceptance as those of financial performance. In this paper it is explored how standard-based evaluation methods may be used to test the underlying theory of change of microfinance, and the rate of use of existing methods in practice. Our findings suggest that social rating and social performance assessment using SPI4 are the most used methods. Nevertheless, standard-based methods are not suitable to assess the complete magnitude of microfinance social performance. Hence, microfinance social performance cannot rely on standard-based methods only, but need to use specific evaluation frameworks and indicators to fully measure microfinance effectiveness.

Abstract African swine fever (ASF), a disease of obligatory declaration to the World Organization for Animal Health (OIE), has contributed to poverty and underdevelopment of affected areas. The presence of ASF has been historically neglected in Africa, contributing to its uncontrolled expansion and favouring its spread to continental Europe on at least three occasions, the last one in 2007 through the Republic of Georgia. Since then, African swine fever virus (ASFV) has spread to neighbouring countries, reaching the European Union in 2014, China in the summer of 2018 and spreading through Southeast Asia becoming a global problem. Lack of available vaccines against ASF makes its control even more difficult, representing today the number one threat for the swine industry worldwide and negatively affecting the global commerce equilibrium. Main body In this review, we intend to put in perspective the reality of ASF vaccination today, taking into account that investment into ASF vaccine development has been traditionally unattractive, overall since ASF-free areas with large swine industries applied a non-vaccination policy for diseases listed by the OIE. The dramatic situation suffered in Asia and the increasing threat that ASF represents for wealthy countries with large swine industries, has dramatically changed the perspective that both private and public bodies have about ASF vaccinology, although this is controversial. The feasibility of modifying the ASFV genome has led to safe and efficacious experimental recombinant live attenuated viruses (LAVs). The main challenge today will be confirming the safety and efficacy of these technologies in the field, accelerating transfer to the industry for official registration and commercialization. The complexity of ASFV, together with the lack of knowledge about the mechanisms involved in protection and the specific antigens involved in it, requires further investment in research and development. Although far from the efficacy achieved by LAVs, subunit vaccines are the optimal choice for the future. If the world can wait for them or not is a contentious issue. Conclusion Despite their inherent disadvantages, LAVs will be the first technology to reach the market, while subunit vaccines will need much further research to become a successful commercial reality.

Abstract Background Leishmaniases are a group of neglected tropical parasitic diseases, mainly affecting vulnerable populations of countries with poor socioeconomic status. Development of efficient vaccines is a priority due to the increasing incidence of drug resistance and toxicity to current treatments. In the search for a safe and efficient protective vaccine for human and dog visceral leishmaniases, we analyzed the suitability of the immunomodulatory drug sirolimus (SIR) to boost a preventive DNA vaccine against leishmaniasis. SIR is an already marketed drug that has been described to boost immune protection against different disease models and has also emerged as a promising therapeutic drug against L. major. Methods Syrian hamsters were treated with SIR concomitantly with the administration of a DNA vaccine formulation consisting in four plasmids carrying the Leishmania genes LACK, TRYP, PAPLE22 and KMPII, respectively. Two weeks after the last vaccination, the animals were infected intraperitoneally with L. infantum parasites. Five weeks post-infection the parasite load was measured by real-time PCR in target tissues and immune response was evaluated by determining anti-Leishmania specific antibodies in combination with cytokine expression in the spleen. Results Our results show that the DNA vaccine itself efficiently reduced the burden of parasites in the skin (P = 0.0004) and lymph nodes (P = 0.0452). SIR administration also enhanced the protection by reducing the parasite load in the spleen (P = 0.0004). Vaccinated animals with or without SIR co-treatment showed lower IFN-γ expression levels than those found in the spleen of control animals. mRNA expression levels of NOS2 and IL-10 were found to be significantly higher in the vaccinated plus SIR treated group. Conclusions Co-administration of SIR enhances a DNA vaccination regimen against L. infantum, improving the reduction of parasite load in skin, lymph node and spleen. The analysis of immune markers in the spleen after challenge suggests that the trend to recover naïve levels of IFN-γ and IL-10, and the concurrent higher expression of NOS2, may be responsible for the protection induced by our vaccine co-administered with SIR.

This paper provides an update and overview of the Center for Remote Sensing of Ice Sheets (CReSIS) radars and platforms, including representative results from these systems. CReSIS radar systems operate over a frequency range of 14–38 GHz. Each radar system's specific frequency band is driven by the required depth of signal penetration, measurement resolution, allocated frequency spectra, and antenna operating frequencies (often influenced by aircraft integration). We also highlight recent system advancements and future work, including (1) increasing system bandwidth; (2) miniaturizing radar hardware; and (3) increasing sensitivity. For platform development, we are developing smaller, easier to operate and less expensive unmanned aerial systems. Next-generation platforms will further expand accessibility to scientists with vertical takeoff and landing capabilities.

Abstract Student clickstream data—time-stamped records of click events in online courses—can provide fine-grained information about student learning. Such data enable researchers and instructors to collect information at scale about how each student navigates through and interacts with online education resources, potentially enabling objective and rich insight into the learning experience beyond self-reports and intermittent assessments. Yet, analyses of these data often require advanced analytic techniques, as they only provide a partial and noisy record of students’ actions. Consequently, these data are not always accessible or useful for course instructors and administrators. In this paper, we provide an overview of the use of clickstream data to define and identify behavioral patterns that are related to student learning outcomes. Through discussions of four studies, we provide examples of the complexities and particular considerations of using these data to examine student self-regulated learning.

Abstract Background Aging is associated with a high risk for cardiovascular disease. The relation of obesity and risk of cardiovascular events appears to be more closely linked to certain clinical or metabolic phenotypes than to obesity itself. Our aim was to establish whether aging influenced the metabolic phenotypes regarding to cardiovascular risk, evaluated by changes in the intima media thickness-common carotid (IMT-CC), in coronary heart disease (CHD) patients. Methods In this cross-sectional study, 1002 CHD patients were studied at entry from the CORDIOPREV study. We performed carotid ultrasound assessment to obtain their IMT-CC values. Carotid atherosclerosis was considered to exist if IMT-CC > 0.7 mm. Results Age determined a higher IMT-CC, regardless metabolic phenotype (all p