Use of risk chart algorithms for the identification of psoriatic arthritis patients at high risk for cardiovascular disease: findings derived from the project CARMA cohort after a 7.5-year follow-up period.

OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.

Phase separation as a strategy to prevent sulfide-related drawbacks in methanogenesis: performance and energetic aspects.

The establishment of sulfate (SO42-) reduction during methanogenesis may considerably hinder the efficient energetic exploitation of methane, once removing sulfide from biogas is obligate and can be costly. In addition, sulfide generation can negatively impact the performance of methanogens by triggering substrate competition and sulfide inhibition. This study investigated the impacts of removing SO42- during fermentation on the performance of a second-stage methanogenic continuous reactor (R2), comparing the results with those obtained in a single-stage system (R1) fed with SO42--rich wastewater (SO42- of up to 400 mg L-1, COD/SO42- of 3.12-12.50). The organic load (OL) was progressively increased to 5.0 g COD d-1 in both reactors, showing completely discrepant performances. Sulfate-reducing bacteria outperformed methanogens in the consumption for organic matter during the start-up phase (OL = 2.5 g COD d-1) in R1, directing up to 73% of the electron flow to SO42- reduction. An efficient methanogenic activity was established in R1 only after decreasing the OL to 0.625 g COD d-1, after which methanogenesis prevailed by consuming ca. 90% of the removed COD. Nevertheless, high sulfide proportions (up to 3.1%) were measured in biogas. Conversely, methanogenesis was promptly established in R2, resulting in a methane-rich (> 80%) and sulfide-free biogas regardless of the operating condition. From an economic perspective, processing the biogas evolved from R2 would be cheaper, although the techno-economic impacts of managing the sulfur pollution in the fermentative reactor still need to be understood.

Evolutionary relationships, hybridization and diversification under domestication of the locoto chile (Capsicum pubescens) and its wild relatives.

Patterns of genetic variation in crops are the result of multiple processes that have occurred during their domestication and improvement, and are influenced by their wild progenitors that often remain understudied. The locoto chile, Capsicum pubescens, is a crop grown mainly in mid-highlands of South-Central America. This species is not known from the wild and exists only as a cultigen. The evolutionary affinities and exact origin of C. pubescens have still not been elucidated, with hypotheses suggesting its genetic relatedness and origin to two wild putative ancestral Capsicum species from the Central Andes, C. eximium and C. cardenasii. In the current study, RAD-sequencing was applied to obtain genome-wide data for 48 individuals of C. pubescens and its wild allies representing different geographical areas. Bayesian, Maximum Likelihood and coalescent-based analytical approaches were used to reconstruct population genetic patterns and phylogenetic relationships of the studied species. The results revealed that C. pubescens forms a well-defined monotypic lineage closely related to wild C. cardenasii and C. eximium, and also to C. eshbaughii. The primary lineages associated with the diversification under domestication of C. pubescens were also identified. Although direct ancestor-descendant relationship could not be inferred within this group of taxa, hybridization events were detected between C. pubescens and both C. cardenasii and C. eximium. Therefore, although hybrid origin of C. pubescens could not be inferred, gene flow involving its wild siblings was shown to be an important factor contributing to its contemporary genetic diversity. The data allowed for the inference of the center of origin of C. pubescens in central-western Bolivia highlands and for better understanding of the dynamics of its gene pool. The results of this study are essential for germplasm conservation and breeding purposes, and provide excellent basis for further research of the locoto chile and its wild relatives.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Hydrogels with dual sensitivity to temperature and pH in physiologically relevant ranges as supports for versatile controlled cell detachment.

Thermosensitive hydrogels based on the N-vinyl caprolactam (VCL), capable of allowing for cell adhesion and proliferation, as well as non-aggressive detachment by controlled temperature drop, were functionalized with 23 % or lower molar percentages of the cationizable hydrophobic unit 2-(diisopropylamino) ethyl methacrylate (DPAEMA), to obtain networks with dual sensitivity to temperature and pH. The swelling analysis of the systems has shown a transition pK (pKb) close to physiological values, dependent on the temperature of the medium (pKb of 6.6 and 6.9 when the temperature of the medium is above and below the transition temperature VPTT, respectively) and little dependence on the degree of functionalization of DPAEMA. In addition, at temperatures below the transition temperature (VPTT), the systems have shown large swelling variations as a function of the pH (i.e. below and above the pKb), exhibiting greater absorption capacity at pHs below pKb, where the DPAEMA units are cationized. Cytocompatibility and transplant capacity have been evaluated using the C166-GFP endothelial cell line. None of the thermosensitive hydrogels with variable DPAEMA content showed a delay with respect to the control without DPAEMA neither in terms of adhesion nor in proliferation. However, by increasing the percentage of DPAEMA functionalization -and decreasing thermosensitivity-, a correlative decrease in mitochondrial activity was obtained in the transplant, with significant differences for the hydrogels with DPAEMA molar percentage of 3 % or higher. Taking advantage of the proximity of the pKb to the physiological value, we have evaluated the cellular response and the capacity for transplantation after lowering the pH to 6.5, below pKb. A direct relationship of the DPAEMA functionalization degree on the detachment efficiency was observed, since the hydrogels with the highest molar load of DPAEMA showed higher mitochondrial metabolic activity after cell detachment.

Serum Advanced Glycation End Products and Their Soluble Receptor as New Biomarkers in Systemic Lupus Erythematosus.

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE-sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

Chromoproduct approach to achieve environmentally sound management of e-waste plastics: Colombian project case.

Research to prevent releases of brominated flame retardants listed as persistent organic pollutants by the Stockholm Convention (POP-BFRs) was conducted through an international cooperation project in Colombia. Six waste electrical and electronic equipment (WEEE) management facilities implemented: 1) sorting e-waste by product type and color (black, white, and other; henceforth called chromoproducts), 2) sampling test products and their plastic fraction (called sets, separated by polymer type), 3) monitoring mass, bromine and antimony contents by hand-held X-ray fluorescence (XRF) and POP-BFRs such as polybrominated diphenyl ethers (PBDEs) by gas chromatography and mass spectrometry (GC-MS), and 4) differentiated treatment according to categories that used the Restriction of Hazardous Substances in Electrical and Electronic Equipment Directive (RoHS) hazardousness threshold of 1000 mg ∑PBDEs/kg. This scheme led to the proposal of a methodology for WEEE management called the "chromoproduct approach". 994,230 products were managed and grouped into 222 chromoproducts, from which 77 were analyzed: 50 below RoHS hazardousness (BRH), 16 above RoHS hazardousness (ARH), and 11 unknown RoHS hazardousness (URH). XRF indicators using bromine and antimony contents could rule out pollution in BRH chromoproducts; however, categorization still required GC-MS. One ARH plastics sample had 3620 mg ∑PBDEs/kg, while no POP-BFRs were found in the BRH plastics sample. The implementation of the chromoproduct approach traced 153.6 tonnes of ARH plastics. BRH plastics composition was estimated and used in a pilot-scale closed-loop economic activity. The chromoproduct approach seems promising for avoiding POP-BFR releases and promoting the upcycling of recyclable e-waste plastics.

Natural history of craniovertebral abnormalities in a single-center study in 54 patients with Hurler syndrome.

OBJECTIVE: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. METHODS: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. RESULTS: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. CONCLUSIONS: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Neurosurgery residency match for international medical graduates in the United States.

OBJECTIVE: Training of international medical graduates (IMGs) offers opportunities for the US neurosurgery community to engage the global talent pool and impact national and international healthcare. Here, the authors analyzed the time trend of IMGs matching into US neurosurgery programs and identified potential opportunities for enhancing IMG engagement. METHODS: The authors analyzed the National Resident Matching Program (NRMP) match results, NRMP program director (PD) surveys, and applicant surveys from 2013 to 2022. Regression methods were used to analyze time trends. RESULTS: Between 2013 and 2022, the number of US neurosurgery residency positions increased by 17.6% (from 204 to 240). During this period, the percentage of IMGs matching into neurosurgery increased from 3.5% to 7%, translating into a 6.8% increase in the likelihood of a successful IMG match per year (95% CI 0.3%-13.8%, p = 0.042). The likelihoods of a successful match for US MDs and IMGs scoring > 260 on the USMLE Step 1 were > 90% and approximately 55%, respectively. In PD surveys, approximately 90% of PDs indicated that they seldom/never interview or rank IMGs. In terms of factors that influenced the PD decision for interviewing/ranking, IMGs are disadvantaged in several categories, including the ability to secure an audition elective/rotation, and proper letters of recommendation, as well as the influence of the culture on the preconceived perception of poor interpersonal skills. CONCLUSIONS: The number of IMGs matching successfully in neurosurgery has increased marginally during the past decade. The authors outline the challenges that IMGs encounter in this process and suggest strategies for considerations of IMG training in NRMP-associated institutions.

Exchangeable Self-Assembled Lanthanide Antennas for PLIM Microscopy.

Lanthanides have unique photoluminescence (PL) emission properties, including very long PL lifetimes. This makes them ideal for biological imaging applications, especially using PL lifetime imaging microscopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lanthanide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous-soluble, lanthanide antenna, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self-assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self-assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well-established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging.

Peri-operative night-time work of anaesthesiologists: A qualitative study of critical issues and proposals.

BACKGROUND: Qualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking. OBJECTIVES: This study aimed to achieve in-depth understanding of anaesthesiologists' perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks. DESIGN: Qualitative analysis of responses to two open-ended questions. SETTING: Online platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC). PARTICIPANTS: The survey sample consisted of an international cohort of anaesthesiologists. MAIN OUTCOME MEASURES: We identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions. RESULTS: We analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%). CONCLUSION: Overall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targets for improvement measures. Further studies should investigate whether countermeasures can improve patient safety as well as the quality of life of anaesthesia professionals. Regulations to improve homogeneity, safety, and quality of anaesthesia practice at night seem to be urgently needed.

Cancer risk with biologic and targeted synthetic DMARDs in patients with rheumatic diseases and previous malignancies: Results from the BIOBADASER register.

OBJECTIVE: to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95 % confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared. RESULTS: A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95 % CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95 % CI 0.2-1.7)], anti-CD20 [0.4(95 % CI 0.1-1)], or anti-IL6 [1.1(95 % CI 0.5-2.4)], anti-CTLA-4 [1.5 (95 % CI 0.7-3.1) or anti-IL17 [0.7 (95 % CI 0.2-2.4) versus TNFi therapy. CONCLUSIONS: We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.

Efectos de una sesión de juegos reducidos basados en balonmano sobre la atención selectiva, sostenida y amplitud atencional en una muestra de adultos jóvenes / Efeitos de uma sessão de jogo pequeno baseado em handebol na atenção seletiva e sustentada e atenção em uma amostra de adultos jovens / Effects of a small-sided handball game on selective, sustained attention and attentional amplitude in a sample of young adults

Estudios previos han puesto de relieve los efectos crónicos y agudos que el ejercicio físico tiene sobre el funcionamiento cognitivo. Sin embargo, es necesario seguir profundizando para obtener información precisa sobre qué tipo de ejercicio es más favorable sobre determinadas capacidades cognitivas. Así, el objetivo de este trabajo fue analizar los efectos de una sesión de juegos reducidos basados en el balonmano sobre la atención selectiva, sostenida y amplitud atencional en una muestra de adultos jóvenes. Formaron parte de este estudio 52 participantes con edades entre 21 y 25 años (M = 21.83; DT = .94) procedentes de la ciudad de Málaga (España). Se empleó un diseño de investigación cuasiexperimental intersujetos con grupo control y experimental. Mediante análisis estadísticos no paramétricos (U Mann Whitney y Wilcoxon) se trató de explorar los efectos de la sesión de actividad físico/deportiva sobre cuatro pruebas de amplitud atencional, dos de atención selectiva y una de atención sostenida. Los resultados mostraron efectos estadísticamente significativos sobre las pruebas de atención selectiva y amplitud atencional, aunque no en la prueba de atención sostenida. Los hallazgos encontrados sugieren que la actividad físico-deportiva colectiva podría tener un efecto agudo significativo sobre la atención, aunque sería necesario seguir indagando sobre qué dimensiones específicas de la atención, dadas las diferencias encontradas entre unos parámetros y otros. (AU)

Previous studies have highlighted the chronic and acute effects that physical exercise has on cognitive functioning. However, it is necessary to go deeper in order to obtain precise information on what typeof exercise is more favorable for certain cognitive abilities. Thus, the objective of this work was to analyze the effects of a session of small games based on handball on selective, sustained attention and attention span in a sample of young adults. Fifty-two participants between the ages of 21 and 25 (M= 21.83; SD= .94) from the city of Malaga (Spain) took part in this study. A quasi-experimental intersubject's research design was used with a control and experimental group. Using non-parametric statistical analyzes (U Mann Whitney and Wilcoxon) we tried to explore the effects of the physical/sports activity session on four tests of attention span, two of selective attention and one of sustained attention. The results showed statistically significant effects on the selective tests and attention span, although not on the sustained attention test. The findings suggest that collective physical-sporting activity could have a significant acute effect on attention, although it would be necessary to continue investigating the specific dimensions of attention, given the differences found between some parameters and others. (AU)

Estudos anteriores destacaram os efeitos crônicos e agudos que o exercício físico tem no funcionamento cognitivo. No entanto, é necessário aprofundar este conhecimento para obter informações mais precisas sobre qual tipo de exercício mais favorável para determinadas habilidades cognitivas. Assim, o objetivo deste trabalho foi analisar os efeitos de uma sessão de pequenos jogos baseados no andebol na atenção seletiva, sustentada e capacidade de atenção numa amostra de adultos jovens. Cinquenta e dois participantes com idades compreendidas entre 21 e 25 anos (M= 21,83; DP= ,94)da cidade de Málaga (Espanha) participaram deste estudo. Um projeto de pesquisa intersujeitos quase-experimental foi usado com um grupo de controlo e experimental. Através de análises estatísticas não paramétricas (U Mann Whitney e Wilcoxon) procurámos explorar os efeitos da sessão de atividade física/desportiva em quatro testes de capacidade de atenção, dois de atenção seletiva e um de atenção sustentada. Os resultados evidenciaram diferenças estatisticamente significativos nos testes de atenção e seletivos, mas não no teste de atenção sustentada. Os resultadosencontrados sugerem que a atividade físico-desportiva coletiva pode ter um efeito agudo significativo na atenção, embora seja necessário continuar a investigar as dimensões específicas da atenção, dadas as diferenças encontradas entre alguns parâmetros. (AU)

Molecular Identification and Fungal Diversity Associated with Diseases in Hass Avocado Fruit Grown in Cauca, Colombia.

Hass avocado fruit diseases are one of the main marketing constraints in Colombia. To identify and reveal the diversity of fungi associated with diseases in fruits and peduncles, symptomatic samples were collected from 67 farms in the 9 main Hass avocado-producing municipalities of the department of Cauca located in southwestern Colombia. A total of 237 monosporic isolates were obtained that were subjected to DNA extraction, amplification of the ITS region, sequencing and functional diversity analysis based on Hill numbers by municipality and altitude. The results indicated that the genera Pseudocercospora, Diaporthe, Colletotrichum, Neofusiococcum, Lasiodiplodia and Pestatoliopsis were associated with fruit diseases. The genus with the highest number of effective species was Colletotrichum. The ITS region revealed 100% identity of the species Pseudocercospora norchiensis, which was the first report of this pathogen in the crop. There was a greater richness and diversity of associated species in the three municipalities, revealing that the higher the altitude was, the lower the richness and diversity of fungi associated with fruit diseases. These results will provide a better understanding of the identification and diversity of pathogenic microorganisms present in avocado production systems in this region of Colombia.

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells.

Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) survival and function remain unclear. After radiation, leptin receptor-expressing cells, which include a population of SPCs, become localized to hypoxic regions of the bone and stabilize the transcription factor hypoxia-inducible factor-2α (HIF-2α), thus suggesting a role for HIF-2α in the skeletal response to radiation. Here, we conditionally knocked out HIF-2α in leptin receptor-expressing cells and their descendants in mice. Radiation therapy in littermate control mice reduced bone mass; however, HIF-2α conditional knockout mice maintained bone mass comparable to nonirradiated control animals. HIF-2α negatively regulated the number of SPCs, bone formation, and bone mineralization. To test whether blocking HIF-2α pharmacologically could reduce bone loss during radiation, we administered a selective HIF-2α inhibitor called PT2399 (a structural analog of which was recently FDA-approved) to wild-type mice before radiation exposure. Pharmacological inhibition of HIF-2α was sufficient to prevent radiation-induced bone loss in a single-limb irradiation mouse model. Given that ~90% of patients who receive a HIF-2α inhibitor develop anemia because of off-target effects, we developed a bone-targeting nanocarrier formulation to deliver the HIF-2α inhibitor to mouse bone, to increase on-target efficacy and reduce off-target toxicities. Nanocarrier-loaded PT2399 prevented radiation-induced bone loss in mice while reducing drug accumulation in the kidney. Targeted inhibition of HIF-2α may represent a therapeutic approach for protecting bone during radiation therapy.

Associations of dietary vitamin A and C intake with asthma, allergic rhinitis, and allergic respiratory diseases.

BACKGROUND/OBJECTIVES: Asthma and allergic rhinitis (AR) are closely related and considered as allergic respiratory diseases (ARD), and their prevalence has recently increased. Data on the association of dietary antioxidant vitamin intake with asthma and AR in adults are limited. The present study aimed to investigate the associations of vitamin A and C intake with asthma, AR, and all cases of both diseases in young adults who participated in a cross-sectional national survey, with the use of high-sensitivity C-reactive protein (hs-CRP) level as an effect modifier. SUBJECTS/METHODS: This study included 6,293 male and female adults aged 20-49 years from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2016 and 2018. The questionnaire-based reports on asthma and AR diagnosis were used to determine outcome variables. Further, 24-h recall data on dietary vitamin A and C, carotene, and retinol intake were acquired. Logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence interval (CI). RESULTS: Dietary vitamin C intake was inversely associated with asthma prevalence among participants with hs-CRP levels (≥ 1 mg/L); the OR of asthma prevalence was 0.27 (95% CI, 0.08-0.84) for participants with vitamin C consumption ≥ 75 mg/day compared with those consuming < 20 mg/day. Similar association analyses limiting to non-users of dietary supplements were performed to rule out the potential effects of supplement intake on the outcomes; results showed a stronger association. However, the association between vitamin C and asthma was not significant in participants with hs-CRP levels < 1 mg/L; the OR of asthma was 1.44 (95% CI, 0.66-3.16) for participants with vitamin C consumption ≥ 75 mg/day compared with those consuming < 20 mg/day. Vitamin C intake was not associated with AR. Moreover, there was no association between vitamin A intake and neither asthma nor AR. CONCLUSIONS: These findings suggest that higher vitamin C intake may play a potential role in reducing asthma prevalence. Nevertheless, further studies should be conducted to evaluate whether this association is causal.

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Severe Asthma and Biological Therapies: Now and the Future.

Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.