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Objective We investigated the bidirectional relationship between rheumatoid arthritis (RA) and periodontitis and their cross‐sectional association using national administrative health care data. Methods The sample included 3,308,903 individuals aged 20 to 79 years who resided in Denmark in 2000 and had remained free of RA and periodontitis in the previous 10 years. RA and periodontitis were defined using diagnosis and treatment codes. Marginal structural survival models were employed to estimate the effects of RA on periodontitis incidence and vice versa from 2000 to 2017. Using a cross‐sectional sample of 2,574,536 individuals from 2017, the association of periodontitis with RA was investigated using regression analyses and probabilistic quantitative bias analyses, simulating RA and periodontitis misclassification and unmeasured confounding of smoking. Results Between 2000 and 2017, 20,348 individuals developed RA and 740,799 developed periodontitis. The estimated hazard ratio (HR) for the effect of periodontitis on incident RA was 1.05 (95% confidence interval [CI] 0.88–1.25), resulting in a restricted mean survival time difference of one day. The HR for the effect of RA on incident periodontitis was 0.84 (95% CI 0.80–0.88), corresponding to a restricted mean survival time difference of 151 days. Cross‐sectionally, the unadjusted prevalence ratio for the association was 1.15 (95% CI 1.11–1.19), whereas the estimate adjusted for measured and simulated confounding was practically null (0.99, 95% simulation interval 0.93–1.04). Conclusion These findings challenge previously reported bidirectional relationships between periodontitis and RA, pointing to potential residual confounding as an important link and prompting reconsideration of the biologic plausibility and clinical significance of these associations.

SUMMARY: Poultry litter amendments are commonly used to mitigate ammonia levels by binding and reducing ammonia volatilization in poultry housing, but there are concerns that litter amendments may impact broiler health. The goal of our study is to characterize the effect of an organic-certified diatomaceous earth litter amendment on the microbial content of the litter, and the gastrointestinal microbiome and leg health of fast-growing broilers. The study was carried out over a 2-yr period involving 5 consecutive flocks housed in a barn, where one half of the barn received the litter amendment while the other half served as a control. Key health indicators such as gastrointestinal microbiome diversity, and leg health were monitored. The findings suggest that the organic litter amendment, while not significantly altering the bacterial counts in the litter, may offer benefits in improving broiler wellbeing. This is evidenced by differences in footpad dermatitis and hock burn scores between the treated and control groups, highlighting the potential of such amendments not only in managing ammonia levels but also in promoting animal health. This study provides valuable insights into the applied implications of using an organic diatomaceous earth amendment in a poultry facility, indicating a positive impact on bird welfare without altering the microbial balance within the litter.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

We present a laser–plasma electron accelerator module designed to be driven by high-repetition-rate lasers for industrial applications of laser-driven electron beams. It consists of a single vacuum chamber containing all the necessary components for producing, optimizing, and monitoring electron beams generated via laser wakefield acceleration in a gas jet when driven by a suitable laser. The core methods in this paper involve a comprehensive metrological assessment of the driving laser by rigorous temporal laser pulse characterization and contrast measurements, supplemented by detailed spatiotemporal distribution analyses of the laser focus. Results demonstrate the good stability and reproducibility of the laser system, confirming its suitability for advanced scientific and industrial applications. We further demonstrate the functionality of the laser–plasma accelerator module diagnostics, perform target density characterizations, and time-resolved laser–plasma shadowgraphy. Current limitations of the set-up preventing first electron acceleration are analyzed and an outlook for future experiments is given. Our work is a first step towards the wide dissemination of fully integrated laser–plasma accelerator technology.

IntroductionHerpesvirus infections have been highlighted as emerging diseases affecting wildlife health and the conservation of several taxa. Malignant catarrhal fever (MCF) and infectious keratoconjunctivitis (IKC) are two viruses that infect wild ruminants. Nevertheless, epidemiological data on herpesviruses in South American wild ruminants are limited. An outbreak of caprine gammaherpesvirus-2 (CpHV-2) that recently was suspected as the cause of MCF in southern pudus (Pudu puda) prompted the need to conduct molecular screenings in Chilean cervids to understand the epidemiology of herpesviruses. The aim of this study was to determine the occurrence and genetic diversity of herpesviruses in free-ranging cervids from Chile.MethodsHerpesvirus infection was assessed in antemortem blood samples (n = 86) from pudus (n = 81) and huemuls (Hippocamelus bisulcus) (n = 5), as well as postmortem samples of spleen (n = 24) and lung (n = 3) from pudus, using a nested pan-herpesvirus PCR assay.ResultsCombining all suitable sample types, DNA of pudu gammaherpesvirus-1 was detected in five pudues and five huemuls, with an overall prevalence of 9.90% (n = 10/101; 95% CI = 5.11–17.87%). One pudu tested positive for ovine gammaherpesvirus-2 (n = 1/96; 1.04%; 95% CI = 0.05–6.49%), and one pudu tested positive for a Macavirus sequence with 98.63 similarity to ovine gammaherpesvirus-2 (n = 96; 1.04%; 95% CI = 0.05–6.49%).DiscussionTo the best of our knowledge, this is the first report of a herpesvirus in huemul and of ovine gammaherpesvirus-2 in Chile. Our results also confirm the active circulation of herpesvirus in free-ranging cervids in Chilean Patagonia, and as such, MCF should be considered as a possible cause of disease in free-ranging Chilean pudus and livestock species. Further research is necessary to develop a plan of systematic monitoring (serological and pathological screening) of herpesviruses in Chilean wild and domestic ruminants to understand their diversity and impact on animal health and conservation.

Abstract Purpose The aim of this systematic review was to present the current evidence on the clinical use of single-photon emission computed tomography/computed tomography (SPECT/CT) in the evaluation of noninfected painful knees after knee arthroplasty. Methods Embase, PubMed, Google Scholar, Ovid, Scopus, Science Direct and the Cochrane Database of Systematic Reviews were searched from database inception to May 2022 following the PRISMA guidelines. As a primary outcome, we defined the role of SPECT/CT in the diagnostic approach to noninfected painful knee arthroplasty; as a secondary objective, we described the noninfection-related factors linked to painful knee arthroplasty. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio values and other indicators were calculated; receiver operating characteristic (ROC) curve analysis results and a summary of the areas under the curve (AUCs) from the included studies were reported. A Fagan plot, likelihood ratio plot and Deeks’ funnel plot were generated and analysed. Methodological quality was assessed using the QUADAS-2 tool, and the certainty of evidence was assessed by the GRADE approach. Results A total of 493 publications were identified, of which eight met the inclusion criteria, with a final pooled sample size of 308 patients. The pooled sensitivity and specificity of SPECT/CT in diagnosing the source of pain in painful knee prostheses were 0.86 (95% CI: 0.75–0.93) and 0.90 (95% CI: 0.79–0.96), respectively, with pooled +LR and −LR values of 8.9 (95% CI: 4.11–19.19) and 0.15 (95% CI: 0.09–0.28). The pooled diagnostic odds ratio was 57.35, and the area under the curve was 0.94. SPECT/CT highly accurately identified different sources of pain, such as loosening of the prosthetic components, patellofemoral overloading, instability, malalignment of the components and degeneration of the patellofemoral compartment. The confidence of the estimates was moderate according to the GRADE approach. Conclusion With demonstrated high sensitivity and specificity, as a diagnostic tool, SPECT/CT can identify the source of pain in painful knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment (level of evidence III). These findings have significant clinical repercussions, such as in changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome. We moderately recommend the use of SPECT/CT for identifying the source of pain after knee arthroplasty according to the GRADE assessment. This review was preregistered in Prospero under code CRD42022320457.

Abstract Lameness is a common condition in dairy cattle caused by infectious or noninfectious agents. Joint lesions are the second most common cause of lameness and can be diagnosed in association with the presentation of digit injuries. Fibroblast-like synoviocyte (FLS) are predominant cells of synovia and play a key role in the pathophysiology of joint diseases, thus increasing the expression of proinflammatory mediators. Tumor necrosis factor-alpha (TNF-α) is a potent proinflammatory cytokine involved in cyclooxygenase 2 (COX-2) and proinflammatory cytokine expression in FLS. Previously, TNF-α was demonstrated to increase hypoxia-inducible Factor 1 (HIF-1), a transcription factor that rewires cellular metabolism and increases the expression of interleukin (IL)-6 in bovine FLS (bFLS). Despite this, the proinflammatory effects of TNF-α in bFLS on metabolic reprogramming have been poorly studied. We hypothesized that TNF-α increases glycolysis and in this way controls the expression of IL-6, IL-8, and COX-2 in bFLS. Results first, gas chromatography/mass spectrometry (GC/MS)-based untargeted metabolomics revealed that bTNF-α altered the metabolism of bFLS, increasing glucose, isoleucine, leucine, methionine, valine, tyrosine, and lysine and decreasing malate, fumarate, α-ketoglutarate, stearate, palmitate, laurate, aspartate, and alanine. In addition, metabolic flux analysis using D-glucose-13C6 demonstrated an increase of pyruvate and a reduction in malate and citrate levels, suggesting a decreased flux toward the tricarboxylic acid cycle after bTNF-α stimulation. However, bTNF-α increased lactate dehydrogenase subunit A (LDHA), IL-6, IL-8, IL-1β and COX-2 expression, which was dependent on glycolysis and the PI3K/Akt pathway. The use of FX11 and dichloroacetate (DCA), an inhibitor of LDHA and pyruvate dehydrogenase kinase (PDK) respectively, partially reduced the expression of IL-6. Our results suggest that bTNF-α induces metabolic reprogramming that favors glycolysis in bFLS and increases IL-6, IL-8, IL-1β and COX-2/PGE2.

El objetivo principal de nuestro artículo es realizar un análisis crítico de la noción de representación como fundamento de la generación de hipótesis en la modelización científica. En efecto, mostraremos las inconsistencias que genera este modo de fundamentar la generación de hipótesis en algunos de los más representativos enfoques sobre la representación científica. Dependiendo del enfoque y la definición de representación considerada, mostramos que estas inconsistencias van desde el uso de recursos no lógicos hasta cierta circularidad en las definiciones. La idea que subyace a toda está crítica es que surrogative reasoning debe encontrar sus fundamentos en la lógica misma.

Vaccination against the COVID-19 virus is currently the best option to combat the SARS-CoV-2 pandemic worldwide. However, in addition to logistical and economic barriers, hesitancy to be vaccinated threatens to jeopardize efforts to contain the disease. An increasing number of people in Africa are delaying or rejecting recommended vaccines. Since their launch, COVID-19 vaccines have frequently faced rejection worldwide. In this study, we interviewed 5,174 participants from Chad that were representative of the general population, on their perception of COVID-19 vaccines. The survey was conducted from April to May 2021, before the rollout of the COVID-19 vaccination. We found that 47.9% of respondents were willing to receive the COVID-19 vaccine, 29.8% were undecided and 22.3% would not accept the vaccine. We found that urban residents were much more likely to refuse the vaccine than rural residents. We also observed that distrust of COVID-19 vaccines and mistaken beliefs played a crucial role in the reluctance to be vaccinated. Hesitancy to vaccinate against COVID-19 was strongly associated with lack of knowledge, and acceptance of vaccination was primarily associated with fear of the disease. Finally, we identified population profiles among the undecided and the refractors, which will help in developing strategies to combat COVID-19 vaccine resistance.

Functional recovery after peripheral nerve injuries is critically dependent on axonal regeneration. Several autonomous and non-cell autonomous processes regulate axonal regeneration, including the activation of a growth-associated transcriptional program in neurons and the reprogramming of differentiated Schwann cells (dSCs) into repair SCs (rSCs), triggering the secretion of neurotrophic factors and the activation of an inflammatory response. Repair Schwann cells also release pro-regenerative extracellular vesicles (EVs), but is still unknown whether EV secretion is regulated non-cell autonomously by the regenerating neuron. Interestingly, it has been described that nerve activity enhances axonal regeneration by increasing the secretion of neurotrophic factors by rSC, but whether this activity modulates pro-regenerative EV secretion by rSC has not yet been explored. Here, we demonstrate that neuronal activity enhances the release of rSC-derived EVs and their transfer to neurons. This effect is mediated by activation of P2Y receptors in SCs after activity-dependent ATP release from sensory neurons. Importantly, activation of P2Y in rSCs also increases the amount of miRNA-21 present in rSC-EVs. Taken together, our results demonstrate that neuron to glia communication by ATP-P2Y signaling regulates the content of SC-derived EVs and their transfer to axons, modulating axonal elongation in a non-cell autonomous manner.

The GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulated DNA damage response and the generation of reactive oxygen species (ROS) have been postulated as major drivers of toxicity in C9ORF72 pathogenesis. Telomeres are tandem-repeated nucleotide sequences that are located at the end of chromosomes and protect them from degradation. Interestingly, it has been established that telomeres are sensitive to ROS. Here, we analyzed telomere length in neurons and neural progenitor cells from several induced pluripotent stem cell (iPSC) lines from control subjects and C9ORF72 repeat expansion carriers. We found an age-dependent decrease in telomere length in two-month-old iPSC-derived motor neurons from C9ORF72 carriers as compared to control subjects and a dysregulation in the protein levels of shelterin complex members TRF2 and POT1.

COVID-19 is affecting different countries and populations unequally. In this sense, sub-Saharan countries represent a particularly vulnerable context due to their unique demographic and health circumstances. A holistic approach to Covid-19 is urged, one that considers the social-cultural contexts of people’s lives. Using Social Determinants of Health (SDH) as framework, we explore which variables could explain the differences in health practices regarding the prevention of COVID-19 in Chad, in order to propose recommendations that allow communities to better face future health crises. The study was designed as a cross-sectional survey conducted in N’Djamena, Chad, using a convenience sampling technique that included 2,330 participants. A regression model was fitted to assess the relationship between educational level, gender, and health practices regarding COVID-19. 2,269 participants completed the survey successfully. Participants mean age was 31.04, 61.52% were male, and 40.55% had precarious jobs. 21.38% of participants answered right all questions regarding knowledge and 37.19% followed all preventive measures. Findings show that safe practices regarding COVID-19 depend on right knowledge. Gender influences knowledge mainly through its influence on education. Vulnerability is given by women’s reduced access to education. The SDH approach provide with an exploratory explanation and some recommendations aimed at local authorities. Access to education for all men and women must be improved to increase health practices and better deal with future health crises.

We report evidence for the first generation of XUV spectra from relativistic surface high-harmonic generation (SHHG) on plasma mirrors at a kilohertz repetition rate, emitted simultaneously with energetic electrons. SHHG spectra and electron angular distributions are measured as a function of the experimentally controlled plasma density gradient scale length Lg for three increasingly short and intense driving pulses: 24 fs and a0=1.1, 8 fs and a0=1.6, and finally 4 fs and a0≈2.1, where a0 is the peak vector potential normalized by mec/e with the elementary charge e, the electron rest mass me, and the vacuum light velocity c. For all driver pulses, we observe correlated relativistic SHHG and electron emission in the range Lg∈λ/20,λ/4, with an optimum gradient scale length of Lg≈λ/10. This universal optimal Lg-range is rationalized by deriving a direct intensity-independent link between the scale length Lg and an effective similarity parameter for relativistic laser-plasma interactions.

We study both numerically and experimentally the use of two third-order nonlinear temporal filtering techniques, namely nonlinear ellipse rotation and cross-polarized wave generation, for simultaneous nonlinear spectral broadening and temporal contrast enhancement of mJ energy, 30 fs titanium:sapphire laser pulses in a multi-pass cell. In both cases, a contrast enhancement greater than 3 orders of magnitude is observed, together with record high conversion efficiencies. Careful balancing of nonlinearity and dispersion inside the multi-pass cell helps tune the spectral broadening process and control the post-compressed pulse duration for specific applications.

Proton beams with up to 100 pC bunch charge, 0.48 MeV cutoff energy, and divergence as low as 3° were generated from solid targets at kHz repetition rate by a few-mJ femtosecond laser under controlled plasma conditions. The beam spatial profile was measured using a small aperture scanning time-of-flight detector. Detailed parametric studies were performed by varying the surface plasma scale length from 8 to 80 nm and the laser pulse duration from 4 fs to 1.5 ps. Numerical simulations are in good agreement with observations and, together with an in-depth theoretical analysis of the acceleration mechanism, indicate that high repetition rate femtosecond laser technology could be used to produce few-MeV proton beams for applications.

The interaction of ultraintense laser pulses with an underdense plasma is used in laser-plasma acceleration to create compact sources of ultrashort pulses of relativistic electrons and x rays. The accelerating structure is a plasma wave, or wakefield, that is excited by the laser ponderomotive force, a force that is usually assumed to depend solely on the laser envelope and not on its exact waveform. Here, we use near-single-cycle laser pulses with a controlled carrier-envelope phase to show that the actual waveform of the laser field has a clear impact on the plasma response. The beam pointing of our relativistic electron beam oscillates in phase with the carrier-envelope phase of the laser, at an amplitude of 15 mrad, or 30% of the beam divergence. Numerical simulations explain this observation through asymmetries in the injection and acceleration of the electron beam, which are locked to the carrier-envelope phase. These results imply that we achieve waveform control of relativistic electron dynamics. Our results pave the way to high-precision, subcycle control of electron injection in plasma accelerators, enabling the production of attosecond relativistic electron bunches and x rays.

Background and objective: The progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Material and methods: Patients with CKD stages 3–4 were randomized into controls (n = 12) or intervention (n = 7) group receiving 360 mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. Results: Supplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change following treatment, but serum Mg significantly correlated with the levels of N-terminal propeptide of collagen alpha-1(I) chain (PINP), a marker of bone synthesis. Conclusions: In sum, these results suggest a possible beneficial effect of Mg on vascular compliance with no detrimental effects on bone status. In addition, our results highlight the need to consider monitorization of urinary Mg status in CKD patients. Resumen: Antecedentes y objetivos: La progresión de la enfermedad renal crónica (ERC) supone el desarrollo de alteraciones del metabolismo mineral que están estrechamente relacionadas con eventos cardiovasculares y enfermedad ósea. La hipomagnesemia se asocia con una progresión más rápida de la ERC, así como con otras comorbilidades. Nuestro objetivo fue analizar en pacientes con ERC estadios 3-4 el impacto de la administración de carbonato de magnesio (Mg) sobre la densidad mineral ósea (DMO) y los cambios hemodinámicos asociados a la calcificación vascular (CV). Material y métodos: Los pacientes con enfermedad renal crónica estadios 3-4 se distribuyeron aleatoriamente en los grupos control (n=12) o intervención (n=7), que recibió 360 mg de carbonato de Mg diariamente durante un periodo de 15 meses. Se evaluaron parámetros relacionados con el metabolismo mineral además de la DMO, CV, y velocidad de onda de pulso (VOP). Resultados: La suplementación con Mg produjo un aumento en la excreción urinaria de Mg, mientras que los niveles séricos de Mg permanecieron estables y no se reportaron episodios de hipermagnesemia. Además, no se observaron cambios significativos en cuanto al grado de CV valorado en base al índice de Adragao. No obstante, tanto los niveles séricos como urinarios de Mg se asociaron significativamente con un descenso en la VOP, lo que sugiere un aumento en la distensibilidad vascular. De manera similar, la DMO no se modificó con la administración del tratamiento, pero los niveles séricos de Mg correlacionaron significativamente con los del propétido N-terminal del colágeno tipo I (PINP), un marcador de la síntesis ósea. Conclusiones: En conjunto, estos resultados sugieren un posible efecto beneficioso del Mg sobre la distensibilidad vascular sin efectos negativos a nivel óseo. Además, nuestros resultados subrayan la necesidad de considerar la monitorización del nivel de Mg urinario en pacientes con ERC.

We use essential limits inferior and superior of the nonlinear part of a discontinuous ODE to introduce some novel transversality conditions which imply that Filippov solutions are Carathéodory solutions. We also prove some uniqueness criteria based on different Lipschitz conditions on different parts of the domain separated from one another by boundaries which satisfy certain transversality conditions.

This article examines three novels that use fiction to revise the figure of the Argentine author Leopoldo Lugones: Ricardo Piglia’s Respiración artificial (1980), C. E. Feiling’s Un poeta nacional (1993), and César Aira’s Lugones (2020). These three novels present different portrayals of Lugones, which also mirror their opposing views of the Argentine literary tradition. Piglia, Feiling, and Aira look back at the so-called national poet when self-fashioning themselves as writers and outlining a literary project in a (post)dictatorial scenario. In a cultural field marked by the effects of state terror and neoliberal reform policies, these fictional renderings of Lugones become a means of reflecting on the political past and the future of literature. Ultimately, I argue that Respiración artificial, Un poeta nacional, and Lugones devise a figure of the Argentine author decoupled from the mission of consolidating a national identity that Lugones epitomized for nearly half a century.

The decreasing well-being among doctoral candidates, coupled with a high prevalence of distress problems, is a topic of increasing concern in the field of higher education and research policy. The present study aimed to replicate, implement, and evaluate the effectiveness of The Third Half, a multi-component psychoeducational program in doctoral students. To address the limitations of the pilot study, we conducted a non-randomized controlled study using a repeated measures pre-post design with a total of 97 participants (Mage = 32.5; SD = 8.23), of whom 26 participated in the experimental group. Results showed that Third Half program participants reported significant decreases in indicators of negative affect (F = 4.01; p = .04) and anxiety (F = 4.95; p = .02) compared to the general control group; in the matched sample analysis (n = 20) significant decreases were found in indicators of negative affect (F = 4.72; p = .03), anxiety (F = 4.09; p