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ABSTRACT Objective: The objective of this study was to determine how arch form and interproximal contact size displace mandibular teeth subjected to an anterior component of force (ACF). Methods: Nine finite element models (FEM) of the mandibular arch were developed using Ansys® v. 16.0 software. They were designed to evaluate the effects of three arch forms (triangular, oval, and square) and three contact sizes (point-to-point, 1 mm diameter, and 2 mm diameter). All nine models were subjected to an ACF of 53.8 N (5486 gm). Three-dimensional tooth rotations and displacements of the mandibular teeth were evaluated, from the right first molar to the left first molar. Results: Arch form had a greater effect on tooth movements than contact size. Triangular arches and point-to-point contacts produced the greatest displacements and rotations of teeth. Oval arches with 2 mm wide interproximal contact points showed the greatest stability. The right first premolar showed the greatest displacements in all of the models. Conclusions: Arch form and contact size affect interproximal tooth stability. Teeth are least stable in narrow arches with point-to-point interproximal contacts, and most stable in wider arches with larger contacts.

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people’s lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population. Resumen: El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales y pandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personas a nivel individual y social, así como una importante sobrecarga para el sistema sanitario. El presente documento de consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de la infección por virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidad disponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento de consenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención de la transmisión y en relación con la vacunación) de la gripe, tanto para población pediátrica como para adultos. Este documento de consenso pretende ayudar a facilitar el abordaje clínico, microbiológico y preventivo de la infección por virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad de la población.

Objetivos: Determinar los hallazgos manométricos en el esófago de pacientes con Esclerosis Sistémica (ES). Materiales y Métodos: Estudio descriptivo de corte transversal, realizado en pacientes con diagnóstico de ES atendidos en el Servicio de Reumatología del Hospital Hermanos Ameijeiras, durante el periodo enero 2020 a diciembre 2021 y que accedieron a realizarse manometría. Resultados: De los 86 pacientes, la edad media fue de 49,5 ± 15,3 años, y 94,3% fueron del sexo femenino. El 90,7% presentó trastornos de la motilidad esofágica (TME), principalmente trastorno motor mayor (58,1%) y el esfínter inferior corto (62,8%). La presencia de síntomas (regurgitación, pirosis y disfagia) se relacionaron con la mayoría de las alteraciones manométricas. De la misma forma, el tiempo de evolución de la enfermedad (10,1 ± 9,1 frente a 5,9 ± 5,9 años [p:0,027]), el fenómeno de Raynaud (93,9% frente a 25,0%, [p:0,002]) y la ES difusa (96,2% frente a 82,4% [p:0,039]) fueron mayores en pacientes con TME. Conclusión: Los pacientes con ES difusa, fenómeno de Raynaud, presencia de síntomas y mayor tiempo de evolución de la enfermedad se asociaron con TME.

El sistema de préstamos financieros hacia el sector agropecuario ha experimentado una evolución significativa en términos de su estructura y características a lo largo del tiempo. La fuente de financiamiento desempeña un papel fundamental en el desarrollo y crecimiento de la actividad, proporcionando el capital necesario para financiar la producción, la adquisición de insumos y maquinaria, y otras necesidades relacionadas. El objetivo del presente trabajo es desarrollar un análisis del sistema de préstamos financieros al sector agropecuario nacional y de La Pampa en particular. En los resultados obtenidos, se observa que el sector agropecuario representa alrededor del 16 % del total de préstamos financieros en la economía nacional y del 29 % en La Pampa. Se observa una evolución similar entre los préstamos totales y los del sector agropecuario, con un crecimiento significativo hasta 2013, seguido de una caída hasta 2016 y un repunte hasta 2018. Se destaca la concentración de los préstamos en el sector, principalmente en cultivos y servicios agrícolas.

The province of Buenos Aires (Argentina) introduced its first criminal jury system in 2013. This article discusses the design and initial findings of an ethnographic research project looking at this legal innovation with particular attention to the effects of the introduction of new (lay) actors – and their practices, knowledges, experiences – to the criminal justice system, bringing to the analysis rules, spaces, temporalities and people that are bound by this phenomenon. Focusing on the initial stages of the process – the draw and summoning of prospective jurors and jury selection hearings –, we discuss how material and temporal constraints to fulfill the legal mandate of incorporating lay decision-makers give place to the reshaping and (re)creation of certain roles and positions within the bureaucratic structure. We argue that the jury has become a spectral presence that alters a myriad of existing practices, characters and responsibilities in the criminal justice of Buenos Aires that goes well beyond their verdicts. En el año 2013 se estableció el juicio por jurados en la Provincia de Buenos Aires, Argentina. Este artículo provee una reflexión basada en el diseño y los primeros hallazgos de un proyecto de investigación etnográfica de largo plazo que indaga en los efectos de la incorporación al sistema de justicia penal de nuevos actores (no profesionales del derecho) con sus prácticas, saberes y experiencias, y que integra a su análisis la consideración de las normas, los espacios, las temporalidades y las personas que este fenómeno amalgama. Poniendo el foco en las etapas iniciales del juicio por jurado —las citaciones de candidatos a jurados y la audiencia de selección —buscamos discutir cómo ciertos roles y posiciones dentro de la estructura burocrática se redefinen y (re)crean a partir de condicionamientos materiales y temporales que se presentan al dar cumplimiento a la obligación legal de incorporar la participación ciudadana al proceso judicial. Nuestro argumento es que el jurado se ha vuelto una presencia inmaterial, etérea, que afecta y modifica una variedad de prácticas, piezas y responsabilidades dentro de la justicia penal de Buenos Aires, más allá de su función concreta de alcanzar un veredicto.

ABSTRACT Human leukocyte antigen (HLA) polymorphisms represent the strongest genetic modifier of HIV disease progression. Diverse HLA distributions can lead to distinct HIV control landscapes at the population level. We aimed to describe HLA allele and haplotype frequencies (linkage disequilibrium, LD), CCR5-Δ32 frequency, and the impact of these variants on HIV disease outcome. HLA class I loci were typed at 4-digit resolution, and CCR5 variants were determined in 402 HIV clade B-infected, antiretroviral treatment-naïve individuals from Honduras. HLA LD was assessed using Fisher’s exact test. Using univariable and multivariable analyses, we evaluated HLA associations with HIV plasma viral load (pVL) and CD4 counts. We did not find any effect on HIV control between CCR5 genotypes. The previously defined HLA associations were found to be B*57:01/03, B*42:01, A*25:01, and C*12:03 (protective) and B*53:01 and A*68:01 (risk). Consistent with our previous research in a Mesoamerican HIV cohort, Amerindian B*35:12 was associated with poor HIV control. Other HLA-HIV associations not previously described were C*03:04 and B*08:01, which were associated with higher pVL. Overall, this first report highlights the immunogenetic uniqueness of the Honduras population that expresses Amerindian, Caucasian, and African HLA subtypes. These findings not only support this cohort as ideal for identifying HLA correlates of HIV control but also may improve future research regarding allotransplantation and disease association. IMPORTANCE We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

In this paper we revisit the problem of erasing sensitive data from memory and registers during return from a cryptographic routine. While the problem and related attacker model is fairly easy to phrase, it turns out to be surprisingly hard to guarantee security in this model when implementing cryptography in common languages such as C/C++ or Rust. We revisit the issues surrounding zeroization and then present a principled solution in the sense that it guarantees that sensitive data is erased and it clearly defines when this happens. We implement our solution as extension to the formally verified Jasmin compiler and extend the correctness proof of the compiler to cover zeroization. We show that the approach seamlessly integrates with state-of-the-art protections against microarchitectural attacks by integrating zeroization into Libjade, a cryptographic library written in Jasmin with systematic protections against timing and Spectre-v1 attacks. We present benchmarks showing that in many cases the overhead of zeroization is barely measurable and that it stays below 2% except for highly optimized symmetric crypto routines on short inputs.

Probiotics, including Streptococcus dentisani, have been proposed as an alternative to re-establish the ecology of the oral cavity and inhibit the formation of pathogenic biofilms. The main objective of this work was to assess the probiotic ability of S. dentisani against Streptococcus mutans, Streptococcus mitis, and Candida albicans biofilms. The ability of the strains to form a monospecies biofilm and the probiotic potential of S. dentisani using the competition, exclusion, and displacement strategies were determined. All strains were moderate biofilm producers. The ability of S. dentisani to compete with and exclude S. mutans and S. mitis during biofilm formation was not significant. However, S. dentisani significantly reduced pathologic streptococcal biofilms using the displacement strategy. Also S. dentisani reduced the formation of the C. albicans biofilm mainly through competition and displacement. In vitro, S. dentisani exhibited probiotic potential to reduce the formation of potentially pathogenic biofilms. Further investigation is required to understand the biofilm-inhibiting mechanisms exhibited by this probiotic strain.

Se realizó un trabajo de investigación basado en el Sistema Globalmente Armonizado (SGA), aplicable al inventario de reactivos del Laboratorio de Bioquímica del Politécnico Colombiano Jaime Isaza Cadavid de Medellín; creando un sitio web empleado para la elaboración de las etiquetas y hojas de seguridad facilitando su lectura mediante un código QR. Esta nueva tecnología de información permite observar desde cualquier dispositivo móvil las características químicas de los insumos del laboratorio, los riesgos potenciales para la salud por exposición o contacto accidental, las afectaciones al medio ambiente por vertimiento involuntario, la neutralización de la sustancia en caso de derrame accidental, los primeros auxilios y la disposición final de los residuos generados. Este proyecto presenta ventajas aportadas por el sistema integrado de información, con las herramientas tecnológicas que permiten hoy en día una comunicación ágil y rápida, además de estar inscrito dentro del Plan de Desarrollo 2022-2025 “Calidad Académica y Humana”.

Herein, the synthesis and characterization methods of natural deep eutectic solvents based on monoterpenoids have been presented. Low viscous fluids with suitable physicochemical properties are produced. The materials are non-toxic, biodegradable, and cost-effective. Thus, they can be used to develop sustainable solvents for various processes and can find their applications in various fields. A theoretical study based on quantum chemistry and classical molecular dynamics is used for the nanoscopic characterization of structure, dynamics, and hydrogen bonding. The reported results help analyze the properties of this new family of solvents. The required information for developing structure–property relationships for proper solvent design to form a sustainable chemistry framework is obtained.

The rising global suicide rate presents a major public health concern, resulting in the loss of over 700,000 lives annually. Discrepancies in the impact of suicide among diverse populations underscore the necessity for targeted prevention strategies. Primary care providers (PCPs) play a crucial role in identifying and managing suicide risk, particularly in underserved areas with limited access to mental health care. Educating PCPs about evidence-based interventions and suicide prevention strategies has demonstrated effectiveness in reducing suicide rates. Landmark initiatives in Australia, Sweden, and Hungary have successfully lowered suicide rates by implementing educational programs for PCPs focused on suicide prevention. Denmark, previously afflicted by some of the highest rates globally in the 1980s, has significantly reduced its figures and now ranks among countries with the lowest rates in high-income nations. Collaborative programs involving PCPs and health workers in low-resource regions have also shown promising outcomes in suicide prevention efforts. Enhancing the expertise of PCPs in suicide prevention can fortify healthcare systems, prioritize mental health, and ultimately save lives, contributing to global health endeavors aimed at addressing the pervasive issue of suicide.

Background: Classification of athletes in cerebral palsy (CP) football is a key action that aims to promote the participation of all players by minimizing the impact of their physical disabilities on the outcome of the competition by establishing sports classes. As such, a new research line has been included in the classification process at an international level; that is, the analysis of locomotor demands during competition helps classifiers to understand the para-footballers’ profile. Therefore, the main aim of this systematic review was to summarize the physical and physiological responses of players with CP in different sport classes during competition. Methods: A bibliographic search was conducted using PubMed, SCOPUS, and Web Of Science databases following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PICOS strategy. Results: Six studies meeting inclusion criteria analyzing physical (i.e., total distances, distances at different speeds, high-intensity and short-term actions, change of directions, etc.) and physiological (heart rate (HR), time spent at different zones of maximum HR, etc.) responses. Findings revealed that para-footballers with CP and minimal impairment impact covered greater total and distance above 23.04 km·h−1 and achieved higher maximum speeds during match-play. Notably, no significant differences in physiological responses were observed based on classification. Conclusions: The research suggests that para-footballers with CP and lower physical impairment may exhibit enhanced performance in terms of distance covered and speed during gameplay, highlighting their potential competence in the sport. In addition, the limited number of studies examining the physiological response of para-footballers prevents conclusive results and differentiating between classification groups.

This study aimed to compare the acute effect of four back squat velocity-based training (VBT) protocols in terms of intensity (60% vs. 80% of the one repetition maximum [1RM]) and volume (10% vs. 30% threshold for velocity loss in the set) on the maximal aerobic speed (MAS) estimated from a running track test (RTT) in recreationally trained young adult men and women. Twenty participants (eleven men and nine women) undertook five randomized protocols in separate occasions: (i) RTT alone (control condition); (ii) VBT with 60% 1RM and a 10% velocity loss followed by RTT (VBT60–10 + RTT); (iii) VBT with 60% 1RM and a 30% velocity loss followed by RTT (VBT60–30 + RTT); (iv) VBT with 80% 1RM and 10% velocity loss followed by RTT (VBT80–10 + RTT); (v) VBT with 80% 1RM and 30% velocity loss followed by RTT (VBT80–30 + RTT). All VBT protocols involved three sets with three minutes of rest. The MAS was higher for RTT (control) than VBT60–30 + RTT (p < 0.001; Δ = 3.8%), VBT60–10 + RTT (p = 0.006; Δ = 2.8%), VBT80–10 + RTT (p = 0.008; Δ = 2.7%), and VBT80–30 + RTT (p = 0.019; Δ = 1.9%). No protocol × sex interaction was noted (p = 0.422). Therefore, regardless of sex, MAS is acutely impaired after VBT, especially if the training sets are performed with a low relative load and a high velocity loss threshold.

The use of biostimulants is becoming a useful tool for increasing crop productivity while enhancing nutritional quality. However, new studies are necessary to confirm that the joint application of different types of biostimulants, together with bioactive compounds, is effective and not harmful to plants. This study examined the impact of applying the biostimulant Green Leaves, comprising Macrocystis algae extract and containing a mixture of amino acids, corn steep liquor extract, calcium, and the bioactive compound glycine betaine. The effect of applying two different doses (3 and 5 mL L−1) of this biostimulant was evaluated on lettuce plants, and growth and quality parameters were analyzed along with photosynthetic efficiency, nutritional status, and nutrient efficiency parameters. The application of Green Leaves improved plant weight (25%) and leaf area and enhanced the photosynthetic rate, the accumulation of soluble sugars and proteins, and the agronomic efficiency of all essential nutrients. The 3 mL L−1 dose improved the nutritional quality of lettuce plants, improving the concentration of phenolic compounds and ascorbate and the antioxidant capacity and reducing NO3− accumulation. The 5 mL L−1 dose improved the absorption of most nutrients, especially N, which reduced the need for fertilizers, thus reducing costs and environmental impact. In short, the Green Leaves product has been identified as a useful product for obtaining higher yield and better quality.

Introduction Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease. Methods We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy. Results From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1–6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity. Conclusion There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.

This paper presents an Internet of Things (IoT) architecture for a power aggregator of energy resources in active distribution networks. Two types of algorithms are evaluated and compared: centralized and decentralized control. The former is based on real-time estimation of the demand and subsequent optimization. The latter is based on the Alternating Direction Method of Multipliers (ADMM). Both algorithms were evaluated on an IoT platform consisting of agents implemented on a series of small single-board computers based on Raspberry Pi technology, connected to a centralized computer that emulates the grid. This platform allows realistic evaluation of the algorithms, considering the effects of communication. The main grid considers power losses and the dynamics of inverter-based renewable resources using quasi-dynamic simulation. This type of simulation can be considered real-time for this application. The platform is demonstrated to be flexible and provides a real view of the practical problems that aggregators may face when implementing them in a power distribution network.

Objectives The aim of this study was to create a new Vall d’Hebron Risk Score-II (VH-RS-II) for non-fatal myocardial infarction (MI) and/or cardiac death (CD), excluding patients with coronary revascularisation (CR) during the follow-up.Methods We analysed 5215 consecutive patients underwent gated single photon emission CT (SPECT); 2960 patients (age 64.2±11, male 58.1%) had no previous MI and/or CR, and 2255 patients (age 63.3±11, male 81.9%) had previous MI and/or CR. During a follow-up of 4.3±2.6 years, the cardiac event (MI and CD) was evaluated. This study was reviewed and approved by the ethics committee of our institution (number form trial register, PR(AG)168.2012). To obtain the predictor model, multivariate Cox regression analysis and multivariate logistic regression analysis were used. RS-VH-II was validated with 679 patients.Results In patients without previous MI and/or CR, age (HR: 1.01; p

El artículo da cuenta de los resultados de una indagación basada en el diseño y gestión de actividades para un aula de educación superior, con la intención de hacer realidad los referentes curriculares colombianos en relación con la formación de ciudadanos democráticos desde las clases de Estadística en la Educación Básica y Media. La propuesta se lleva a cabo, a través de un proceso de ejemplificación, reflexión y acción, dirigido a futuros educadores matemáticos, estudiantes de la Licenciatura en Matemáticas que cursan la materia Enseñanza y Aprendizaje de la Estadística en la Universidad Pedagógica Nacional, Colombia. Se busca que, a través de la práctica docente, una vez tomada conciencia del reto como futuros docentes, los participantes aporten a la formación de valores democráticos en los estudiantes a su cargo. A partir de una indagación de índole cualitativa, se evidencia, a través de las intervenciones de los participantes y los diseños de sus planeaciones de clase, que los futuros educadores logran apropiarse de la importancia y necesidad de desarrollar el valor de la Justicia desde la clase de Estadística, identificando en este proceso la función de tal disciplina en la formación de ciudadanos críticos. Como resultados se observa que desde una educación estadística crítica es posible potenciar el valor de la justicia y la apropiación de conocimiento estadístico asociado a la interpretación y análisis de gráficos y tablas estadísticas; y que es factible propiciar, en futuros docentes, una reflexión consciente sobre el papel de la Estadística en la solución de problemáticas reales como estrategia para procurar ciudadanos estadísticamente cultos. Es menester precisar que, para lograr dicha reflexión, re requiere ajustar la secuenciación del currículo para contar con más tiempo del tradicional, así lograr mayor impacto en el proceso de formación democrática y que este se lleve a cabo en su totalidad.

Objectives: To evaluate the impact of a mentoring programme for medical students doing a palliative care rotation, aimed at improving coping with death and attitudes towards the suffering produced by illness. Methods: A quasi-experimental study without a control group was carried out on second-year medical students. Five 1-h group sessions were conducted. Attitudes towards grief and coping with death were assessed before the mentoring programme began and afterwards, using the Brief Humanizar Scale and the Bugen's Coping with Death Scale, respectively. Results: In terms of the sense of grieving as measured by the Brief Humanizar Scale, the mean score for the ‘Burden’ factor was 7 points and for the ‘Change’ factor it was 28.6, indicating that suffering makes more sense as a lever for positive change than as a burden. Regarding Bugen's Coping with Death Scale, the mean score was 127.8 points before the mentoring programme and 139.2 afterwards. Hence, the score after the mentoring programme increased by 11.4 points, improving strategies to cope with death. Conclusion: Medical professionals must cope with death and end-of-life patients. In addition to scientific knowledge, students need to acquire competencies for better coping with the death of patients, with mentoring programmes helping to enhance this process of learning.

Resistance to cisplatin is the main cause of treatment failure in lung adenocarcinoma. Drug-tolerant-persister (DTP) cells are responsible for intrinsic resistance, since they survive the initial cycles of treatment, representing a reservoir for the emergence of clones that display acquired resistance. Although the molecular mechanisms of DTP cells have been described, few studies have investigated the earliest molecular alterations of DTP cells in intrinsic resistance to cisplatin. In this work, we report a gene expression signature associated with the emergence of cisplatin-DTP cells in lung adenocarcinoma cell lines. After a single exposure to cisplatin, we sequenced the transcriptome of cisplatin-DTPs to identify differentially expressed genes. Bioinformatic analysis revealed that early cisplatin-DTP cells deregulate metabolic and proliferative pathways to survive the drug insult. Interaction network analysis identified three highly connected submodules in which SOCS1 had a significant participation in controlling the proliferation of cisplatin-DTP cells. Expression of the candidate genes and their corresponding protein was validated in lung adenocarcinoma cell lines. Importantly, the expression level of SOCS1 was different between CDDP-susceptible and CDDP-resistant lung adenocarcinoma cell lines. Moreover, knockdown of SOCS1 in the CDDP-resistant cell line partially promoted its susceptibility to CDDP. Finally, the clinical relevance of the candidate genes was analyzed in silico, according to the overall survival of cisplatin-treated patients from The Cancer Genome Atlas. Survival analysis showed that downregulation or upregulation of the selected genes was associated with overall survival. The results obtained indicate that these genes could be employed as predictive biomarkers or potential targets to improve the effectiveness of CDDP treatment in lung cancer patients.

BackgroundSaliva modulates the environment of the oral biofilm through pH buffer, microbial attachment to host surfaces, and nutritional source. The ecology of stress occurs when a physical factor adversely impacts an ecosystem or its biotic components. Therefore, reduced salivary flow can affect oral-host balance. The leading causes of hyposalivation include disease-associated Sjögren’s syndrome (SS) and menopausal women as aging-associated. However, little is known about the oral microbiome integrated with sex hormones in hyposalivation. This study aimed to characterize the hyposalivation microbiome caused by aging or disease affecting the salivary glands in women.MethodsWe included 50 women older than 40 years of age in any menopausal phase. We collected stimulated saliva from 25 women diagnosed with SS (SS) and 25 without SS (non-SS). The bacterial profile of the patients was obtained by 16S rRNA sequencing. Bioinformatics analysis used machine learning to analyze the cohort’s signs, symptoms, and bacterial profile. Salivary estradiol as a sex hormone variation level was determined.ResultsWe obtained that 79% of the SS group, and 52% of the non-SS group had hyposalivation. We found a negatively correlated Prevotella-age and Rothia-estradiol in the SS group. Highlight, we found that the cause of the hyposalivation in the study did not explain differences in microbial diversity comparing non-SS and SS groups. Therefore, microbial communities found in hyposalivation but not related to systemic conditions suggest that changes in the oral environment might underpin host-microbial balance.ConclusionThe salivary microbiome was similar in women with and without SS. However, hyposalivation showed two distinctive clusters associated with the bacterial population profiles. Our study suggests that local ecological disturbances could drive the change in the microbiome.

Introduction: In Spain, 2 million people are treated for obstructive sleep apnoea. Continuous positive airway pressure, the gold-standard therapy, requires regular follow-up and periodic evaluation of the efficacy of the treatment via a titration examination, i.e. autoCPAP test. Telemonitoring use is increasing and this study aims to evaluate the cost impact of its use for therapy evaluation instead of the standard ambulatory autoCPAP test. Material and methods: This prospective observational study includes 100 OSA patients under CPAP therapy who volunteered to test telemonitoring as an alternative therapy control tool. Costs for both the patients and the Sleep Unit were calculated and compared for the standard of care (ambulatory autoCPAP (SoC)), vs alternative telemonitoring option (TM). Results: More than half (54%) of the patients preferred the TM option vs only 47.5% of the SoC patients. Patients inclining towards telemonitoring option were mainly reported to be more than 10 years youngers, mainly active workers (63%), travelling more distance to the Sleep Unit (16 vs 8 km) and spending more expenses in travel than those who preferred SoC (median 30€). 29% of active workers left their jobs to attend the SoC. The costs related to the use of the Sleep Unit resources were found to be lower in the TM option compared to the SoC option (0.47 vs 3.09 euros per patient attended). Conclusions: The use of TM for follow-up CPAP therapy enables the patient to save travel costs and to reduce absenteeism but also to save assistential burden and therefore to reduce the Sleep Unit workload and optimize the care activity.

The term free-water volume fraction (FWVF) refers to the signal fraction that could be found as the cerebrospinal fluid of the brain, which has been demonstrated as a sensitive measure that correlates with cognitive performance and various neuropathological processes. It can be quantified by properly fitting the isotropic component of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using N=287 healthy subjects (178F/109M) aged 25-94, this study examines in detail the evolution of the FWVF obtained with the spherical means technique from multi-shell acquisitions in the human brain white matter across the adult lifespan, which has been previously reported to exhibit a positive trend when estimated from single-shell data using the bi-tensor signal representation. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the spherical means-based multi-shell FWVF parameter with age, at the same time, a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW corrected diffusion tensor imaging (DTI) leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to the studies conducted over the standard (single-component) DTI. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the conceivable reason for the variations observed in FA and MD parameters across the lifespan with previous studies under the standard diffusion tensor imaging.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

BackgroundDiabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets.Methods and findingsRat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1β, IL1β+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1β and vitamin D in β-cells. These include Ri-lnc1, which is enriched in mature β-cells.ConclusionsOur results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on β-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic β-cells and downregulated by IL1β treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in β-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.

En esta entrevista la Catedrática de la Universidad de Sevilla Encarnación Aguilar Criado responde a una serie de cuestionamientos sobre ruralidad, calidad alimentaria y tradición mediante una mirada retrospectiva a su excelsa trayectoria académica, intelectual y vital. Sus reflexiones comienzan con la descripción de sus primeros trabajos sobre género y producción doméstica de las bordadoras de los mantones de manila en Sevilla, hasta llegar a sus investigaciones sobre calidad alimentaria, tradición e innovación desde el punto de vista de los productores en los entornos rurales. En esta entrevista, la autora hace mención también a las diferentes investigadoras/es e intelectuales que la han acompañado a lo largo de estos años, permitiéndonos comprender, y contextualizar, el trabajo desarrollado durante toda una vida académica dedicada a la docencia y la investigación desde la mirada de la Antropología Social.

Introduction: The circadian system regulates various physiological processes such as sleep-wake cycles, hormone secretion, metabolism, and the reaction to both natural and drug-based rewards. Chronic disruption of the circadian system caused by unsteady synchronization with light-dark (LD) schedules, such as advancing chronic jet lag (CJL), leads to adverse physiological effects and pathologies, and is linked with changes in mood and depressive behaviors in humans and rodent models.Methods: C57BL/6J male mice were subjected to circadian disruption through phase advances of 6 h every 2 days (CJL +6/2). Mice under 12:12-h LD cycle were used as controls. After 8 weeks under these conditions, a battery of behavioral tests was performed to assess if mood-related behaviors were affected.Results: Compared to controls under 24 h LD cycles, mice under CJL presented desynchronization of activity-rest rhythms that led to several behavioral impairments, including a decrease in motivation for food reward, and an increase in anxiety, anhedonia, and depressive-like behavior.Conclusion: Chronic circadian disruption, caused by an experimental CJL protocol, affects mood-related and reward-related behaviors in mice. Understanding the importance of the circadian system and its potential role for disruption due to CJL is important for maintaining good health and well-being.

Background: Synovial sarcoma (SS) is part of soft tissue sarcomas (STS). An incidence between 5% to 10% is estimated. The origin is mesenchymal mainly affecting the extremities. Being even rarer at the chest level and vertebral body, representing around 1%. Histologically, it consists of 3 variants: monophasic, biphasic, and poorly differentiated. Surgical resection is a priority when it comes to multidisciplinary management. The prognosis of patients with SS over the years has improved markedly. Purpose: Understand and evaluate the multidisciplinary management of SS considering that the SS has a lowe prevalence and highly malignancy. Study Design: We present a case of a 31-year-old male who has a history of monophasic synovial sarcoma diagnosed in 2019 and underwent surgery. Patient came back after two years without symptoms and posterior to a control MRI we observed a local recurrence of SS. Methods: The literature was reviewed with a focus on best clinical and surgical strategy for recurrence of SS. Results: The patient recovered well with return to his normal daily activities. The review of the literature shows us the importance of the multidisciplinary management for the optimal clinical and surgical approach of SS recurrence. Conclusions: SS represents a unique variant of STS, with malignant and metastatic potential. Being a rare pathology, an adequate multidisciplinary management is essential when providing optimal care for the patient.

Multiple sclerosis is a frequent condition where the diagnosis relies on clinical presentation, neurologic examination, cerebro spinal fluid markers, and diagnostic imaging tests; however, atypical variants of the disease can lead to misdiagnosis in some scenarios. Herein, we describe a case of a 24-year-old patient with multiple sclerosis with megacystic plaques, in which appropriate interpretation of the imaging findings lead to a proper diagnosis and treatment.

The increasing penetration of renewable generation in power systems is causing growing concern about system stability. Grid-forming (GFM) control has been appointed as the technology required for achieving a high penetration of renewables in the grid, as it successfully contributes to the power system stability. This paper proposes a novel grid-forming control scheme for voltage source converters (VSC) achieving the operational characteristics of a virtual synchronous machine (VSM). The proposed scheme is based on the orientation of a defined virtual flux to a reference axis obtained from the emulation of the synchronous generator swing equation. The virtual flux is obtained by the integration of the VSC internal voltage and it is oriented to the reference axis by means of a flux controller that also controls the flux magnitude. In this way, the VSC synchronism is maintained, operating as a voltage source connected to the grid. Moreover, the flux orientation in turn allows to control the VSC active power, while the flux magnitude control allows to regulate the VSC reactive power or terminal voltage in isolated mode. The paper also demonstrates that the stability of GFM converters is negatively affected when emulating high inertia values. So, a stabilizer is also proposed for damping these modes. Finally, due to fact that GFM converters behave as voltage sources, their low voltage ride through capability becomes an issue, because they naturally respond to faults with high short-circuit currents, that cannot be withstand by power electronics converters. Therefore, a method for limiting fault currents is proposed as well in the paper. The proposed grid-forming control scheme has been implemented in a real-time control platform and validated using comprehensive simulation models in a real-time simulator for assessing its grid-forming capability.

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Abstract Background Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. Results We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. Conclusion We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.

El objetivo de este trabajo se enfoca en analizar las dimensiones dominantes de las formas de fondo simuladas mediante un modelo hidrodinámico tridimensional acoplado con procesos de transporte de partículas y metodologías numéricas de utilidad para estimar los cambios en la morfología de flujos con superficie libre. En este sentido, se aplicaron técnicas de estadística descriptiva y espectral a las geometrías de fondo simuladas, obteniendo una discretización espacial y temporal de las dimensiones dominantes en el dominio de estudio del río Tercero en su paso por la ciudad de Villa María, Argentina. Las características del tramo seleccionado corresponden a las de un río de aguas poco profundas y con pendiente de fondo acorde con la de un cauce de planicie.

Este documento está centrado en determinar qué variables afectan los incentivos que tienen los delincuentes al cometer sus ciberdelitos, e identificar si la legislación actual está diseñada teniendo en cuenta la tipificación de las conductas y las herramientas de los entes encargados de capturar los criminales. Se busca entender los principales factores que incentivan la ciberdelincuencia en el país, teniendo en cuenta el contexto de la ciberdelincuencia para el 2019 en Colombia, y con ello, el comportamiento de los delincuentes informáticos en la prepandemia. Con la Ley 1273 de 2019, encargada de tipificar los delitos informáticos en Colombia, se revisarán los datos reportados de delitos informáticos y se compararán con los casos e indicadores de delitos de hurto calificado, con el fin de determinar la relación de estos dos delitos, que son relevantes para las entidades y han sido interiorizados por las entidades policivas en su estudio y lucha anticriminal desde hace mucho tiempo. Una vez definida teóricamente la eficiencia de las entidades apoderadas en la lucha contra los delitos informáticos, se propone una función de beneficios económicos de la ciberdelincuencia adaptada para el caso colombiano, determinando las variables que mejor explican esta función. Al final de este ejercicio académico, mediante un análisis de sensibilidad, se señala qué aspectos de política pública se deben considerar como prioritarios, teniendo en cuenta los incentivos económicos para los ciberdelincuentes y la efectividad de la Ley 1273 de 2009.

Abstract In the present study, a comparative human toxicity assessment between newly developed Mn3O4 nanoparticles with enhanced electrochemical properties (GNA35) and their precursor material (Mn3O4) was performed, employing different in vitro cellular models representing main exposure routes (inhalation, intestinal and dermal contact), namely the human alveolar carcinoma epithelial cell line (A549), the human colorectal adenocarcinoma cell line (HT29), and the reconstructed 3D human epidermal model EpiDerm. The obtained results showed that Mn3O4 and GNA35 harbour similar morphological characteristics, whereas differences were observed in relation to their surface area and electrochemical properties. In regard to their toxicological properties, both nanomaterials induced ROS in the A549 and HT29 cell lines, while cell viability reduction was only observed in the A549 cells. Concerning their skin irritation potential, the studied nanomaterials did not cause a reduction of the skin tissue viability in the test conditions nor interleukin 1 alpha (IL- 1 α) release. Therefore, they can be considered as not irritant nanomaterials according to EU and Globally Harmonized System of Classification and Labelling Chemicals. Our findings provide new insights about the potential harmful effects of Mn3O4 nanomaterials with different properties, demonstrating that the hazard assessment using different human in vitro models is a critical aspect to increase the knowledge on their potential impact upon different exposure routes.

Objectives: We evaluated the VE and the mutations of the viruses present in the Mexican population at the beginning of 2018. Methods: We diagnosed influenza in outpatients with a high-performance Rapid Influenza Diagnostic Test (RIDT) qRT–PCR. Descriptive statistics were used to describe the study population, while the chi-square test was used to determine clinical variables. VE was analyzed through a negative test design. We sequenced the hemagglutinin (HA) gene, performed a phylogenetic analysis, and analyzed the nonsynonymous substitutions both in and outside antigenic sites. Results: Of the 240 patients analyzed, 42.5% received the trivalent vaccine, and 37.5% were positive for influenza. The VE for the general population for any influenza virus type or subtype was 37.0%, while the VE for the predominant influenza A(H3N2) subtype was the lowest (19.7%). The phylogenetic analysis of HA showed the co-circulation of clades and subclades 3C.2a1, 3C.2a1b, 3C.2a2, 3C.2a2re, 3C.2a3, and 3C.3a with identities approximately 97-98% similar to the vaccine composition. Conclusion: Low VE was related to the co-circulation of multiple clades and subclades of influenza A(H3N2), with sufficient genetic and phenotypic distance to allow for the infection of vaccinated individuals.

Background: Pathologic acetabular defects can undermine the stability and osseointegration of a primary total hip arthroplasty (THA) acetabular component. Our service has used photodynamic nails (PDNs) in a modified Harrington technique to provide space-filling stability to a primary acetabular implant without impeding local osseointegration. Here we describe our experience with PDN-augmented THAs. Methods: An institutional review board-approved retrospective analysis of all patients who underwent PDN-augmented THA in the management of severe (Harrington class II or III) acetabular defects from September 1, 2020 to May 1, 2021 with at least 6 months of follow-up was performed. The primary outcome was implant survivorship. Comparisons between preoperative and 6-week postoperative visual analogue pain scores were made using the Mann-Whitney U test. Results: Six patients were included in this case series, 5 with metastatic cancer and 1 with pelvic discontinuity and avascular necrosis following failed attempted acetabular fixation. The mean follow-up duration was 10.3 ± 4.3 months. The mean age was 75.5 ± 4.7 years, mean body mass index 27.3 ± 5.6, and 5 patients were female. All but 1 patient was American Society of Anesthesiologists (ASA) class III. Two patients required acetabular revisions, one for aseptic loosening and a second for a pathologic fracture secondary to disease progression. One patient passed away 90 days after the procedure. The mean visual analogue pain score significantly improved from 7.8 ± 1.6 to 2.0 ± 1.4 six weeks after surgery (P = .008). Conclusions: PDN augmentation of the periacetabular bone of patients with large pelvic defects yields durable pain relief and function in vulnerable hosts. PDN should be considered a part of the reconstructive surgeon’s armamentarium.

Abstract Covalent modifications of standard DNA/RNA nucleobases affect epigenetic regulation of gene expression by modulating interactions between nucleic acids and protein readers. We derive here the absolute binding free energies and analyze the binding modalities between key modified nucleobases 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N6-methyladenine (m6A) and all non-prolyl/non-glycyl protein side chains using molecular dynamics simulations and umbrella sampling in both water and methanol, the latter mimicking the low dielectric environment at the dehydrated nucleic-acid/protein interfaces. We verify the derived affinities by comparing against a comprehensive set of high-resolution structures of nucleic-protein complexes involving 5mC. Our analysis identifies protein side chains that are highly tuned for detecting cytosine methylation as a function of the environment and can thus serve as microscopic readers of epigenetic marks. Conversely, we show that the relative ordering of sidechain affinities for 5hmC and m6A does not differ significantly from those for their precursor bases, cytosine and adenine, respectively, especially in the low dielectric environment. For those two modified bases, the effect is more nuanced and manifests itself primarily at the level of absolute changes in the binding free energy. Our results contribute towards establishing a quantitative foundation for understanding, predicting and modulating the interactions between modified nucleic acids and proteins at the atomistic level.

Designing and understanding quantum materials requires continuous feedback between experimental observations and theoretical modelling. Here, a machine learning scheme integrates experiments with theory and modelling on experimental timescales for extracting material parameters and properties of Dy2Ti2O7 spin-ice under pressure.

Abstract Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.

Abstract Background SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. Methods In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. Results Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. Conclusions Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

Barley β-d-glucan glucohydrolase is a glycoside hydrolase family 3 (GH3) enzyme critical for growth and development. Here the authors carryout mutagenesis, structural analyses and multi-scale molecular dynamics to examine the binding and conformational behaviour of several β-d-glucosides during the substrate-product assisted catalysis that operates in GH3 hydrolases.

Aicardi syndrome is an X-linked-dominant genetic condition that is present almost exclusively in females. To diagnose Aicardi syndrome, the classic triad of agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae must be present. Here, we described a case of a female newborn baby delivered at 36 weeks of gestation that arrived at the emergency department with stiffening of arms and legs; therefore, an electroencephalogram was performed, showing generalized polypots confirming infantile spasms. Moreover, magnetic resonance was performed, showing complete agenesis of the corpus callosum. The patient was then transferred for an ophthalmoscopic examination, which evidenced multiple hypopigmented chorioretinal lesions corresponding to chorioretinal lacunae. Based on the clinical and radiological findings, the diagnosis of Aicardi syndrome was established, and treatment with anticonvulsive therapy and physiotherapy was initiated. This case report highlights the main characteristics that clinicians should consider to suspect this rare genetic condition, emphasizing the imaging and electroencephalographic findings.

IntroductionOur understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children.MethodsWe enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata.ResultsChildren had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively).ConclusionThe gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

La paquidermodactilia es una fibromatosis de los tejidos blandos de las articulaciones interfalángicas proximales, caracterizada por ser asintomática y simétrica, se presenta con mayor frecuencia en hombres jóvenes. Su etiología es incierta, pero existen factores que predisponen su aparición. Es una patología benigna cuyo diagnóstico es clínico, por lo que su reconocimiento oportuno, evita el uso de exámenes complementarios innecesarios y costosos, su diagnóstico diferencial se enfoca principalmente en enfermedades reumáticas. Presentamos el caso de un paciente masculino de 31 años con edema fusiforme bilateral de las articulaciones interfalángicas proximales de 16 años de evolución.

In the development of water resources projects with large hydraulic infrastructures, alterations to the natural flow regime will increase the erosive processes on the discharge structures due to variability of the turbulent velocities and the particle transport. We analyzed the case of the Mazar dam, a project designed to regulate the solid and liquid flows that come from the Paute river basin. Erosive processes of great magnitude are generated in the stilling basin of Mazar dam, due to the intensity of turbulent velocities produced in extreme events. We applied the Delft3D numerical model to simulate the hydrodynamic and sediment transport conditions to evaluate the stability conditions of the Mazar dam stilling basin. With the results obtained, vulnerable zones have been identified in the stilling basin. We recommended mitigation measures with the installation of a geomembrane to reduce the erosive processes in the vulnerable zones.