A New Tool for Assessing Environmental Impacts of Altering Short-Term Flow and Water Level Regimes

The computational tool InSTHAn (indicators of short-term hydrological alteration) was developed to summarize data on subdaily stream flows or water levels into manageable, comprehensive and ecologically meaningful metrics, and to qualify and quantify their deviation from unaltered states. The pronunciation of the acronym refers to the recording interval of input data (i.e., instant). We compared InSTHAn with the tool COSH-Tool in a characterization of the subdaily flow variability of the Colorado River downstream from the Glen Canyon dam, and in an evaluation of the effects of the dam on this variability. Both tools captured the hydropeaking caused by a dam operation, but only InSTHAn quantified the alteration of key flow attributes, highlighting significant increases in the range of within-day flow variations and in their rates of change. This information is vital to evaluate the potential ecological consequences of the hydrological alteration, and whether they may be irreversible, making InSTHAn a key tool for river flow management

Alveolar ridge preservation for further rehabilitation with implants: case report

SUB-HEADING: Alveolar ridge preservation is done when immediate or early implant placement is not indicated. PURPOSE: Report a case of extraction of the maxillary premolar, followed by alveolar preservation and later rehabilitation with implants. CASE REPORT: A 52-year-old male patient sought care for the rehabilitation of upper left second premolar tooth, which had a longitudinal fracture. The radiographic examination revealed the proximity of the root apex to the floor of the maxillary sinus and alveolar preservation was chosen. CONCLUSION: The clinical decision-making process for preservation starts before extraction.  INTRODUÇÃO: Preservação alveolar é realizada quando a instalação de implante imediata ou precoce não é indicada. OBJETIVO: Relatar um caso de extração de um pré-molar superior, seguido pela preservação alveolar e posterior reabilitação com implante. RELATO DE CASO: Paciente do sexo masculino, 52 anos,  necessitando da reabilitação do segundo pré-molar superior esquerdo, que possuía uma fratura longitudinal. O exame radiográfico, revelou proximidade do ápice radicular com o assoalho do seio maxilar e a preservação alveolar foi o tratamento de escolha. CONCLUSÕES: O processo de decisão clinica para a preservação alveolar deve iniciar antes da extração

Luces y sombras de la Guía Europea ESC-2021 de Prevención de la Enfermedad Cardiovascular en la Práctica Clínica

General practitioners see in their consultation a a significant number of patients at high vascular risk (VR). The European Guidelines for Cardiovascular Disease Prevention (2021) recommend a new risk classification and intervention strategies on on vascular risk factors (RF), with the aim of providing a shared decision-making recommendations between professionals and patients. In this document we present a critical analysis of these guidelines, offering possible solutions that can be implemented in Primary Care. It should be noted that there are positive aspects (lights) such as that the SCORE2 (from forty to sixty-nine years) and SCORE2-OP models (from seventy to eighty-nine years) are based on more current cohorts and measure cardiovascular risk in a more accurately manner. In addition, it is proposed to differentiate different risk thresholds according to age-groups. For sake of practicality, cardiovascular risk can be estimated using different websites with the new computer models. However, among the negative aspects (shadows), it seems to be add complexity implementing nine subgroups of subjects according to their age or level of risk, with a defined thresholds that could cause a substantial increase in the potential number of subjects susceptible to treatment without a clear evidence that supports it. In addition, two-step RF interventions could delay achievement of therapeutic goals, especially in very high-risk patients, diabetics, or patients with cardiovascular disease. Given these limitations, in this document we propose practical recommendations in order to simplify and facilitate the implementation of the guideline in primary care.Los médicos de familia atienden un importante número de pacientes con alto riesgo vascular (RV). Las Guías Europeas de Prevención Cardiovascular (2021) proponen una nueva clasificación del riesgo y estrategias de intervención sobre los factores de riesgo (FRV), orientada a la toma de decisiones compartidas entre profesionales y pacientes. En el presente trabajo realizamos un análisis crítico de dichas guías, ofreciendo posibles soluciones prácticas para la Atención Primaria. Son destacables aspectos positivos (luces) que los modelos de RV SCORE2 (entre cuarenta y sesenta y nueve años) y SCORE2-OP (entre setenta y ochenta y nueve años) se basan en cohortes más actuales y miden con mayor exactitud y discriminación dicho riesgo. Además, se propone actuar diferenciadamente sobre el riesgo según la edad. Pragmáticamente, se presentan nuevos modelos informáticos para calcular el riesgo. Sin embargo, entre los aspectos negativos (sombras), parece colegirse una mayor dificultad de implementación al proponerse nueve subgrupos de sujetos según su edad o nivel de riesgo, con un dintel definitorio de alto RV subjetivo que podría ocasionar un incremento sustancial en el número de sujetos susceptibles de tratar sin una discriminación objetiva que lo sustente. Además, las intervenciones sobre los FRV en dos pasos podrían retrasar la consecución de objetivos terapéuticos, sobre todo en pacientes de muy alto riesgo, diabéticos o con enfermedad cardiovascular. Ante las dificultades que plantea la valoración del riesgo, proponemos unificar criterios y simplificar los mensajes claves para hacer unas guías más atractivas y que realmente ayuden a los profesionales de Atención Primaria en su práctica habitual

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with the origin and progression of neurodegenerative disorders such as Parkinson’s disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates the cellular response to oxidative stress. The regulation of NRF2 signalling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson’s disease. The NRF2 pathway has been shown to be affected in patients with this disease, and activation of NRF2 has neuroprotective effects in preclinical models, demonstrating the therapeutic potential of this pathway. In this review, we highlight recent advances regarding the regulation of NRF2, including the effect of Angiotensin II as an endogenous signalling molecule able to regulate ROS production and oxidative stress in dopaminergic neurons. The genes regulated and the downstream effects of activation, with special focus on Kruppel Like Factor 9 (KLF9) transcription factor, provide clues about the mechanisms involved in the neurodegenerative process as well as future therapeutic approaches