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Purpose of Review: The prevalence of benign prostatic hyperplasia (BPH) is rising, however, current treatment options present severe complications and limit patient's quality of life. Accordingly, advancements in prostatic catheter and stent designs for use in treating lower urinary tract symptoms (LUTS) in BPH patients have largely expanded in the past five years and we aim to provide an exhaustive summary of recent outcomes., Recent Findings: The dual dilation and paxlitaxel eluting Optilume BPH Catheter System enhances promise in catheter-based treatments, providing the longest sustained increase in max urinary flow rate and decrease in post-void residual volume compared to alternative MISTs. Additionally, use of iTiND, along with recent advancements in temporary (EXIME, Prodeon Urocross) and permanent (Zenflow Spring, Butterfly, and ClearRing) stent designs, have demonstrated rapid, lasting, and low-cost LUTS relief with sustained sexual function. Minimally invasive solutions that offer in-office treatment, rapid symptom relief, shorter recovery times, and preservation of sexual function hold great promise in improving outcomes in managing BPH patients with LUTS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Benign prostatic hyperplasia (BPH) is prevalent in nearly 70% of men over the age of 60, leading to significant clinical challenges due to varying symptom presentations and treatment responses. The decision to undergo surgical intervention is not straightforward; the American Urological Association recommends consideration of surgical treatment after inadequate or failed response to medical therapy. This review explores the role of artificial intelligence (AI), including machine learning and deep learning models, in enhancing the decision-making processes for BPH management., Recent Findings: AI applications in this space include analysis of non-invasive imaging modalities, such as multiparametric Magnetic Resonance Imaging (MRI) and Ultrasound, which enhance diagnostic precision. AI models also concatenate serum biomarkers and histopathological analysis to distinguish BPH from prostate cancer (PC), offering high accuracy rates. Furthermore, AI aids in predicting patient outcomes post-treatment, supporting personalized medicine, and optimizing therapeutic strategies. AI has demonstrated potential in differentiating BPH from PC through advanced imaging and predictive models, improving diagnostic accuracy, and reducing the need for invasive procedures. Despite promising advancements, challenges remain in integrating AI into clinical workflows, establishing standard evaluation metrics, and achieving cost-effectiveness. Here, we underscore the potential of AI to improve patient outcomes, streamline BPH management, and reduce healthcare costs, especially with continued research and development in this transformative field., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Baseball is one of the most popular sports among youth athletes in the United States, and among these players, pitchers are at a particularly high risk of sustaining an injury. Overuse of the arm from repetitive pitching is a common mechanism for injury. Despite the attention that overuse injury has received, little is known regarding the mechanism that leads to elbow injury. This study aims to determine the effect of increasing pitch count on elbow flexion at ball release in a youth pitching cohort. The authors hypothesize that elbow flexion would increase as pitch count increases., Methods: Study subjects included volunteers from youth baseball players from local teams and public advertisements. Retroreflective markers attached to bony landmarks were placed on the players according to International Shoulder Group recommendations. Pitchers threw an indoor simulated game. Three-dimensional marker trajectories were collected using a 12-camera optical motion capture system, and ball velocity was captured using a radar gun. Voluntary maximal isometric strength of the internal and external rotators was evaluated before and after pitching. Paired 2-tailed t tests were performed to determine if a significant change occurred between the fresh and fatigued sets., Results: Twelve adolescent male pitchers were recruited. Eleven of 12 pitchers completed the prescribed 6 sets of 15 pitches, culminating in a 90-pitch simulated game. The ball speed in the second set was found to be the highest in all pitchers and was considered the "peak set" (P = .021), whereas ball speed was the slowest in the sixth set of pitches and was therefore considered the "fatigue set" (P = .001). There was a moderate but statistically significant inverse correlation between elbow flexion at ball release and maximum internal rotation velocity (P = .005). Elbow flexion at ball release was also significantly positively correlated with shoulder abduction at ball release (P = .004). Elbow flexion at ball release was not significantly correlated with ball velocity (P = .108)., Conclusions: In a simulated game laboratory setting, increasing pitch count was associated with increasing elbow flexion angle at ball release in youth baseball pitchers. These findings demonstrate that pitching with fatigue may cause biomechanical changes that have been associated with increased rates of elbow injury in the adult throwing population. Further investigation on the association between elbow flexion angle and elbow injury in the youth baseball population is needed., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: Although acute and preventive treatments for migraine are commonly given in combination, data on the real-world effectiveness of ubrogepant as an acute treatment when used with an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (with or without onabotulinumtoxinA) are limited. This analysis sought to evaluate the real-world effectiveness, treatment satisfaction, and optimization of ubrogepant for the acute treatment of migraine when used in combination with an anti-CGRP monoclonal antibody, with or without concomitant onabotulinumtoxinA., Methods: This prospective, multiple-attack, open-label, observational study (COURAGE) assessed meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization of ubrogepant (50 or 100 mg) when combined with an anti-CGRP monoclonal antibody, onabotulinumtoxinA, or both in adult users of Migraine Buddy, a migraine tracking application., Results: In the ubrogepant and anti-CGRP monoclonal antibody arm (n = 245), following the first ubrogepant-treated attack, 61.6% (151/245) and 80.4% (197/245) of ubrogepant-treated participants achieved MPR at 2 and 4 h post-dose, respectively, and 34.7% (85/245) and 55.5% (136/245) achieved RNF at 2 and 4 h post-dose, respectively. Across up to 10 ubrogepant-treated attacks (N = 1153), MPR was achieved in 51.3% (592/1153) and 73.5% (847/1153) at 2 and 4 h post-dose, respectively. RNF was achieved by 32.2% (371/1153) and 53.2% (613/1153) at 2 and 4 h post-dose. After 30 days, 72.7% (168/231) of participants reported satisfaction (using a 7-point scale) with ubrogepant when used in combination with an anti-CGRP monoclonal antibody, and 79.7% (184/231) of participants achieved acute treatment optimization (defined as moderate-maximum treatment efficacy using the Migraine Treatment Optimization Questionnaire-4)., Conclusion: Real-world ubrogepant use with an anti-CGRP monoclonal antibody was associated with MPR, RNF, satisfaction, and acute treatment optimization., (© 2023. The Author(s).)

Pain is one of the key non-motor symptoms experienced by a large proportion of people living with Parkinson's disease (PD), yet the mechanisms behind this pain remain elusive and as such its treatment remains suboptimal. It is hoped that through the study of animal models of PD, we can start to unravel some of the contributory mechanisms, and perhaps identify models that prove useful as test beds for assessing the efficacy of potential new analgesics. However, just how far along this journey are we right now? Is it even possible to model pain in PD in animal models of the disease? And have we gathered any insight into pain mechanisms from the use of animal models of PD so far? In this chapter we intend to address these questions and in particular highlight the findings generated by others, and our own group, following studies in a range of rodent models of PD., (Copyright © 2024. Published by Elsevier Inc.)

Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication, but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations. Here, we used single-cell DOGMA-seq to simultaneously capture transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4 + T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription factor [IRF] and activator protein 1 [AP-1]). A proliferation program (IKZF3, IL21, BIRC5, and MKI67 co-expression) promoted the survival of transcriptionally active HIV-1-infected cells. Both latent and transcriptionally active HIV-1-infected cells had increased IKZF3 (Aiolos) expression. Distinct epigenetic programs drove the heterogeneous cellular states of HIV-1-infected cells: IRF:activation, Eomes:cytotoxic effector differentiation, AP-1:migration, and cell death. Our study revealed the single-cell epigenetic, transcriptional, and protein states of latent and transcriptionally active HIV-1-infected cells and cellular programs promoting HIV-1 persistence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes - International Study., Methods: This cross-sectional, observational, web-based survey was conducted in 2021-2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases., Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4-7, 8-14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither., Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment., (© 2023. The Author(s).)

Purpose: Composite models have become commonplace for the assessment of fixation and stability of total joint replacements; however, there are no comparable models for the cervical spine to evaluate fixation. The goal of this study was to create the framework for a tunable non-homogeneous model of cervical vertebral body by identifying the relationships between strength, in-fill density, and lattice structure and creating a final architectural framework for specific strengths to be applied to the model., Methods: The range of material properties for cervical spine were identified from literature. Using additive manufacturing software, rectangular prints with three lattice structures, gyroid, triangle, zig-zag, and a range of in-fill densities were 3D-printed. The compressive and shear strengths for all combinations were calculated in the axial and coronal planes. Eleven unique vertebral regions were selected to represent the distribution of density. Each bone density was converted to strength and subsequently correlated to the lattice structure and in-fill density with the desired material properties. Finally, a complete cervical vertebra model was 3D-printed to ensure sufficient print quality., Results: Materials testing identified a relationship between in-fill densities and strength for all lattice structures. The axial compressive strength of the gyroid specimens ranged from 1.5 MPa at 10% infill to 31.3 MPa at 100% infill and the triangle structure ranged from 2.7 MPa at 10% infill to 58.4 MPa at 100% infill. Based on these results, a cervical vertebra model was created utilizing cervical cancellous strength values and the corresponding in-fill density and lattice structure combination. This model was then printed with 11 different in-fill densities ranging from 33% gyroid to 84% triangle to ensure successful integration of the non-homogeneous in-fill densities and lattice structures., Conclusions: The findings from this study introduced a framework for using additive manufacturing to create a tunable, customizable biomimetic model of a cervical vertebra., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

The persistent condition of COVID-19 is characterized by a wide range of symptoms that have had a significant impact on both the health status and occupational life of the population. In this observational and multicenter study, the relationship between the sociodemographic and clinical profile of Spanish patients diagnosed with long COVID, and the work-related disability resulting from this pathology was analyzed. The analysis included 689 responses. A descriptive analysis of the variables recorded was performed, together with a bivariate analysis to determine associations between work-related disability and variables such as gender, age, health status, disabling symptoms or comorbidities. The results obtained highlight fatigue and lack of concentration (brain fog) as the most incapacitating symptoms among patients diagnosed with long COVID. Multivariate analysis revealed that time since diagnosis (OR: 0.57, CI95%: 0.36-0.89, p : 0.013), concomitant renal insufficiency (OR: 4.04, CI95%: 1.42-11.4, p : 0.008), and symptoms like fatigue (OR: 0.56, CI95%: 0.33-0.99) and tremors (OR: 2.0, CI95%: 1.06-3.69, p : 0.029), were associated with work-related disability. These findings highlight the need to improve the health and work-related management of this condition in the healthcare system. Besides risk factor control, it is suggested to pay special attention to determining the appropriate timing of medical leave work reintegration, along with coordination between primary care and occupational health services to ensure the gradual and tailored return of patients with long COVID to the workforce.

Background: The obstructive sleep apnea syndrome (OSA) is a highly prevalent condition. In Spain and other countries, only 5%-9% of patients with OSA have been diagnosed and treated. The lack of accessibility to diagnosis is considered the main cause of this situation through easy-to-use screening instruments, it is necessary to check their validity and reliability in the context where they are to be used., Objective: To validate the Spanish translation of the Berlin questionnaire for screening for moderate or severe OSA in patients aged 40 years or more detected in primary care., Methods: A descriptive observational study, with a first qualitative phase of transcultural adaptation to Spanish using the translation-back-translation method. Setting: primary care level of the Spanish National Health System. A total of 255 patients recruited from 7 healthcare centers completed the study. The Berlin questionnaire was administered to the recruited patients, and subsequently, a respiratory polygraphy was performed to confirm the diagnosis of OSA. The concurrent criterion validity of the questionnaire and its reliability in terms of internal consistency and reproducibility (intra-observer agreement) were analyzed., Results: The patients' mean age was 54.76 years (SD: 6.57; 95% CI: 53.53-54.99), and 54.12% were men (95% CI: 47.96-60.27). We found that 61.57% (95% CI: 55.57-67.57) presented OSA (apnea-hypopnea index-AHI >5), and 45.5% (95% CI: 17.05-57.92) presented moderate or severe (AHI >15) OSA. The Berlin questionnaire, with a cut-off point of 4.5, showed a sensitivity of 76.77% (95% CI: 67.94-85.59), a specificity of 74.49% (95% CI: 65.35-83.63), a positive predictive value of 75.25% (95% CI: 66.34-84.16), a negative predictive value of 76.04% (95% CI: 66.98-85.10), and an area under the curve of 0.786 (95% CI: 0.721-0.851). Cronbach's alpha coefficient was 0.730 (95% CI: 0.668-0.784), and the Kappa index was 0.739 (95% CI, 0.384-1.000)., Conclusion: The Spanish adaptation of the Berlin questionnaire has good validity and reliability as a test for the diagnostic screening of moderate or severe OSA in patients aged 40 years or older. The findings of our study confirm that primary care physicians should use such screening tools to predict OSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Navarrete-Martínez, Muñoz-Gómez, Serrano-Merino, Perula-de Torres, Vaquero-Abellán, Silva-Gil, Roldán-Villalobos, Martín-Rioboó, Ruiz-Moruno, Romero-Rodríguez, González-Lama and Montes-Redondo.)

Background: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited., Methods: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4)., Results: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%., Conclusions: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Health professionals have been one of the groups most affected by the SARS-CoV-2 virus. Currently, there is little scientific evidence on the similarities and differences between COVID-19 infection and the development of long COVID in primary care (PC) workers. Therefore, it is necessary to analyse their clinical and epidemiological profiles in depth. This study was observational and descriptive, including PC professionals who were divided into three comparison groups based on the diagnostic test for acute SARS-CoV-2 infection. The responses were analysed using descriptive and bivariate analysis to examinate the relationship between independent variables and the presence or not of long COVID. Binary logistic regression analysis was also conducted, with each symptom as the dependent variable and each group as the independent variable. The results describe the sociodemographic characteristics of these population groups, revealing that women in the health sector are the most affected by long COVID and that being in this group is associated with its development. Furthermore, individuals with long COVID exhibited the highest number of symptoms and pathologies. Certain symptoms were found to be associated with long COVID development in this population, including an altered sense of smell, pneumonia, fever, and sore throat, among others. Similarly, altered senses of smell and taste, chest tightness, and joint pain, among others, were found to be associated with acute COVID-19 infection. Additionally, patients with pre-existing overweight or obesity were more likely to experience acute COVID-19 and develop long COVID. The data obtained can be crucial for improving the detection, diagnosis, and treatment of long COVID patients, ultimately leading to an enhancement in their quality of life.

During meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between chromatin accessibility and transcription through prophase I of mammalian meiosis by measuring genome-wide patterns of chromatin accessibility, nascent transcription, and processed mRNA. We find that Pol II is loaded on chromatin and maintained in a paused state early during prophase I. In later stages, paused Pol II is released in a coordinated transcriptional burst mediated by the transcription factors A-MYB and BRDT, resulting in ~3-fold increase in transcription. Transcriptional activity is temporally and spatially segregated from key steps of meiotic recombination: double strand breaks show evidence of chromatin accessibility earlier during prophase I and at distinct loci from those undergoing transcriptional activation, despite shared chromatin marks. Our findings reveal mechanisms underlying chromatin specialization in either transcription or recombination in meiotic cells., (© 2023. The Author(s).)

Persistent COVID-19 condition includes a wide variety of symptoms and health problems of indeterminate duration. The present study examined the sociodemographic and clinical characteristics of the population with Long COVID seen in Primary Care using a questionnaire based on the existing scientific literature. It was an observational and descriptive study of the characteristics of the Spanish population with Long COVID over 14 years of age. The responses were analysed by means of a descriptive analysis of the variables recorded, in addition to a bivariate analysis to determine the existence of a relationship between persistent COVID-19 and variables such as gender, age, vaccination status or concomitant pathology. The results obtained clearly describe the sociodemographic characteristics of the population, highlighting the predominance of female gender and the prevalence of tiredness and fatigue. Furthermore, relevant information was obtained on the differences in symptomatology according to gender, age, previous pathologies and alterations derived from infection and/or vaccination. These data are important for better detection, diagnosis and treatment of Long COVID and the improvement of the quality of life of this population.

Background: Acute abdomen in pregnancy (AAP) is defined as intensive abdominal pain lasting less than 24 hours that may require urgent surgery. It is a challenging situation to diagnose and manage, as it is associated with pain due to the normal anatomical and physiological changes that occur during pregnancy., Objective: Therefore, understanding these changes and their effect on almost every system, will help us appreciate the upcoming causes of AAP, mainly the non-obstetric surgical emergencies (e.g., appendicitis, cholecystitis)., Methods: This article highlights the importance of the well-rounded care that should be offered to every pregnant patient presenting to any center with a Non-obstetric Acute Abdomen. The causes are discussed separately (for surgical pearls), laparoscopic approach and radiologic modality decision-making in pregnancy, which is an academic and a practice-based helpful summary., Results and Discussion: This article highlights the importance of the well-rounded care that should be offered to every pregnant patient presenting to any center with a Non-obstetric Acute Abdomen. The causes are discussed separately (for surgical pearls), laparoscopic approach and radiologic modality decision-making in pregnancy, which is an academic and a practice-based helpful summary. Results and Discussion: In addition, the sequence of ideas and language used in the article was based to help the reader understand the topic, rather than inform them about it. In addition, the utility of laparoscopy in pregnancy remains a concern due to the possible risk of injury to the fetus and fetal acidosis. Although, trials showed that laparoscopy was associated with less blood loss and a shorter hospital stay. Moreover, in some cases radiographic imaging is necessary, posing a diagnostic dilemma., Conclusion: AAP is a major concern that requires early interventions to pinpoint the cause and manage the patient, properly., Competing Interests: None declared., (© 2023 Humood A. Alsadery, Omar A. Bamalan, Hussain J. Aljubran, Lama J. Albaish, Basmah Z. Al Ghanim.)

The germline mobilization of transposable elements (TEs) by small RNA mediated silencing pathways is conserved across eukaryotes and critical for ensuring the integrity of gamete genomes. However, genomes are recurrently invaded by novel TEs through horizontal transfer. These invading TEs are not targeted by host small RNAs, and their unregulated activity can cause DNA damage in germline cells and ultimately lead to sterility. Here we use hybrid dysgenesis-a sterility syndrome of Drosophila caused by transposition of invading P-element DNA transposons-to uncover host genetic variants that modulate dysgenic sterility. Using a panel of highly recombinant inbred lines of Drosophila melanogaster, we identified two linked quantitative trait loci (QTL) that determine the severity of dysgenic sterility in young and old females, respectively. We show that ovaries of fertile genotypes exhibit increased expression of splicing factors that suppress the production of transposase encoding transcripts, which likely reduces the transposition rate and associated DNA damage. We also show that fertile alleles are associated with decreased sensitivity to double-stranded breaks and enhanced DNA repair, explaining their ability to withstand high germline transposition rates. Together, our work reveals a diversity of mechanisms whereby host genotype modulates the cost of an invading TE, and points to genetic variants that were likely beneficial during the P-element invasion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The objective was to determine the plasma concentrations of ionized Ca (iCa) and Mg (iMg) and to establish the prevalence of subclinical hypocalcemia (SCHC) and hypomagnesemia (SCHM) in dairy cows at calving (within 6 hours of parturition) and at 7 days postpartum (pp) in Chilean grazing herds with spring parturitions. Plasma iCa and iMg were assessed using a clinical analyzer. A total of 113 and 175 cows in 18 herds selected at random were sampled at calving and at 7 days pp, respectively. From these 18 herds, 11 herds provided reliable records of lactation number and 8 cows per herd were scored for body condition and sampled at calving and then at 7 days pp. Ionized Ca concentrations for the 18 herds were 0.99 ± 0.16 mmol/L (calving) and 1.01 ± 0.13 mmol/L [7 d pp (P > 0.05)]. Ionized Mg concentrations were 0.58 ± 0.12 mmol/L and 0.51 ± 0.09 mmol/L (P ≤ 0.05). For the 11 herds, iCa concentrations at calving were 1.06 mmol/L (lactation 1), 1.02 mmol/L (lactation 2) and 0.89 mmol/L (lactation ≥ 3), while iMg concentrations were 0.63 mmol/L, 0.60 mmol/L, and 0.61 mmol/L, respectively. Herd prevalence for SCHC (iCa < 1.0 mmol/L) at calving was 64.8%. Prevalence by parity was 40%, 54.5% and 86.7% for lactations 1, 2 and ≥ 3, respectively. Herd prevalence of SCHC on day 7 pp was 30.1%. For SCHM (iMg < 0.52 mmol/L) prevalence was 21.6% and 48.9% at calving and at 7 days pp, respectively., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Pedro Melendez reports was provided by Texas Tech University. Pedro Melendez reports a relationship with Texas Tech University that includes: employment, (© 2022 Published by Elsevier Ltd.)

Background: Since the beginning of the COVID-19 pandemic, a great variability of symptoms that affect all organs and systems of the body has been identified in patients with SARS-CoV-2 infection; this symptomatology can sometimes persist over time, giving rise to the so-called long COVID or post-COVID. The aim of this study is to delve into the clinical characterization of these patients, as well as to take into account the influence of factors such as hospitalization, admission to ICU, history of pneumonia, or vaccination status on the persistence of symptoms., Material and Methods: An observational, descriptive, multicenter, and retrospective study was designed with a series of cases of people who presented long COVID, which includes univariate, bivariate, and multivariate analyses. Data were obtained from an online ad hoc questionnaire, and statistical analysis was performed using SPSS Software Version 25 (IBM-Inc., Chicago, IL, USA)., Results: Hospitalization, ICU admission, history of pneumonia, and vaccination were predictive factors (positive or negative) for the following long-COVID symptoms: headache, menstrual disorders, joint pain, cough, chills, nasal congestion, back pain, abdominal pain, weight loss, eye discomfort, facial erythema, itching, tremors, dizziness, seizures, sleeping difficulty, dry eyes, palpitations, fatigue, paresthesia, dyspnea, aphonia, chest pain, high blood pressure, vomiting, memory loss, brain fog, hypothermia, low blood pressure, sputum or phlegm, lack of concentration, hair loss, and erectile dysfunction., Conclusion: This study provides evidence on the clinical characterization of patients suffering from long COVID in order to offer them the most appropriate treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Romero-Rodríguez, Pérula-de Torres, Castro-Jiménez, González-Lama, Jiménez-García, González-Bernal, González-Santos, Vélez-Santamaría, Sánchez-González and Santamaría-Peláez.)

Background: Pain is a common non-motor symptom of Parkinson`s disease (PD), however, its pathomechanism remains elusive., Objective: We aimed to investigate the local gene expression of selected proinflammatory mediators in patients with PD and correlated our data with patients`pain phenotype., Methods: We recruited 30 patients with PD and 30 healthy controls. Pain intensity of patients was assessed using the Numeric Rating Scale (NRS) and patients were stratified into PD pain (NRS≥4) and PD No Pain (NRS<4) subgroups. Skin punch biopsies were immunoassayed for protein-gene product 9.5 as a pan-neuronal marker and intraepidermal nerve fiber density (IEFND). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to assess the gene expression of inflammatory mediators in the skin compared to controls., Results: Patients with PD had lower distal IENFD compared to healthy controls. In skin samples, IL-2 (p<0.001) and TNF-α (p<0.01) were expressed higher in PD patients compared to controls. IL-1β (p<0.05) was expressed higher in the PD pain group compared to healthy controls. PD patients with pain receiving analgesics had a lower expression of TNF-α (p<0.05) in the skin compared to those not receiving treatment., Conclusions: Our data suggest the occurrence of a local, peripheral inflammatory response in the skin in PD, but do not support this being a relevant factor contributing to pain in PD., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Sleep apnea-hypopnea syndrome (OSA) is a highly prevalent disease and has been related to cardiovascular diseases and occupational and traffic accidents. Currently, it is estimated that there is a significant underdiagnosis of OSA, mainly due to the difficulty accessing the tests for that purpose., Objective: To determine the usefulness of the Spanish version of the STOP-Bang questionnaire (SBQ) for screening for moderate or severe OSA in the adult population attending primary care., Methods: A descriptive observational multicenter study was conducted. Through an opportunistic search, (patients over 18 years old), were recruited in seven primary care centers. The SBQ was applied to them and home respiratory polygraphy (HRP) was subsequently performed to confirm the diagnosis of OSA. The criterion validity of the SBQ was analyzed, comparing the score obtained by the SBQ with the apnea-hypopnea index (AHI) obtained by RP, establishing the diagnosis of OSA for an AHI>5. The reliability of the questionnaire was evaluated., Results: A total of 255 subjects, 54.1% men, with a mean age of 54.76 ± 10 years, were recruited in the study. The results showed that 61.57% (95% Confidence Interval: 55.57-67.57) of the subjects presented OSA, presenting 22.75% (17.57-57.92) a mild OSA (530) (11.54-20.62). The Kuder and Richardson coefficient was 0.623 (0.335-0.788) and Cohen's Kappa coefficient was 0.871 (0.520-1.00; p < 0.001). For moderate/severe OSA screening (AHI>15) the SBQ obtained an ROC curve of 0.769 (0.704-0.833) that with an optimal cutoff of 3, achieved a sensitivity of 84.85% (77.28-92.42) and a specificity of 55.10% (44.74-65.46)., Conclusions: The SBQ is very effective for detecting moderate/severe OSA. Its psychometric properties are similar to those obtained in studies on other populations. Because of its ease of use, the SBQ is a very useful tool for primary health care professionals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muñoz-Gómez, Navarrete-Martínez, Serrano-Merino, Silva-Gil, Roldán-Villalobos, Martín-Rioboó, Ruiz-Moruno, Romero-Rodríguez, Gonzalez-Lama, Vaquero-Abellán and Perula-de-Torres.)

Purpose: Patients with diabetes mellitus have an increased risk of developing various serious health problems that could be life-threatening. These problems are associated with the difficulty of these patients in managing their lifestyle, which may even lead to the abandonment of treatment. The present study was designed to evaluate the feasibility of a multipurpose activity control solution for home activity (home activity control system), which will provide information on the activities of daily living carried out outside in real time, to improve adherence to each of the therapeutic objectives agreed on with the diabetic patient., Patients and Methods: A pilot randomised controlled feasibility study will be carried out to evaluate a home activity control system (Beprevent) in managing patients with type 2 diabetes mellitus. Twenty patients with type 2 diabetes mellitus will be included (10 in the intervention group and 10 in the control group). Data on satisfaction with the tool will be collected from professionals and patients, as well as other clinical/epidemiological data from their digital health records and several questionnaires, at baseline and six months. In addition, data will also be recorded regarding the degree of adherence to the behaviors agreed on with the patients before starting the study to assess changes throughout the study and their relationship with clinical results (glycosylated haemoglobin (HbA1c), cholesterol, etc), and to compare these outcomes between two study groups., Discussion: This project involves the incorporation of telemedicine in the management of patients with diabetes. Thus, according to the currently published bibliography, the use of smart devices in this population could help improve the quality of life of these people, reduce medical visits and improve adherence to home care patterns for diabetes mellitus. There are currently no published clinical trials or protocols that monitor activities of daily living in patients with diabetes individually using artificial intelligence (AI) devices., Competing Interests: The authors report no conflicts of interest in relation to this work., (© 2022 Montagut-Martínez et al.)

Background: NLRP3-driven inflammatory responses by circulating and lung-resident monocytes are critical drivers of asthma pathogenesis. Autophagy restrains NLRP3-induced monocyte activation in asthma models. Yet, the effects of autophagy and its master regulator, transcription factor EB (TFEB), on monocyte responses in human asthma remain unexplored. Here, we investigated whether activation of autophagy and TFEB signaling suppress inflammatory monocyte responses in asthmatic individuals., Methods: Peripheral blood CD14 + monocytes from asthmatic patients (n = 83) and healthy controls (n = 46) were stimulated with LPS/ATP to induce NLRP3 activation with or without the autophagy inducer, rapamycin. ASC specks, caspase-1 activation, IL-1β and IL-18 levels, mitochondrial function, ROS release, and mTORC1 signaling were examined. Autophagy was evaluated by LC3 puncta formation, p62/SQSTM1 degradation and TFEB activation. In a severe asthma (SA) model, we investigated the role of NLRP3 signaling using Nlrp3 -/- mice and/or MCC950 administration, and the effects of TFEB activation using myeloid-specific TFEB-overexpressing mice or administration of the TFEB activator, trehalose., Results: We observed increased NLRP3 inflammasome activation, concomitant with impaired autophagy in circulating monocytes that correlated with asthma severity. SA patients also exhibited mitochondrial dysfunction and ROS accumulation. Autophagy failed to inhibit NLRP3-driven monocyte responses, due to defective TFEB activation and excessive mTORC1 signaling. NLRP3 blockade restrained inflammatory cytokine release and linked airway disease. TFEB activation restored impaired autophagy, attenuated NLRP3-driven pulmonary inflammation, and ameliorated SA phenotype., Conclusions: Our studies uncover a crucial role for TFEB-mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection., Methods: In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models., Results: There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P  = 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml., Conclusion: This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM parasomnia that often predicts the later occurrence of alpha-synucleinopathies. Variants in the gene encoding for the lysosomal enzyme glucocerebrosidase, GBA, strongly increase the risk of RBD. In a GBA1-mouse model recently shown to mimic prodromal stages of α-synucleinopathy, we now demonstrate striking REM and NREM electroencephalographic sleep abnormalities accompanied by distinct structural changes in the more widespread sleep neurocircuitry., (© 2022. The Author(s).)

Background: Very positive effects have been described in the application of pain neuroscience education (PNE) to chronic pain and migraine. However, there are few data on the applicability of this therapeutic approach in actual clinical practice in a primary care (PC) setting. The aim of this study was to explore the efficacy in fibromyalgia (FM) of an intervention based on PNE and exercise compared to treatment as usual (TAU)., Methods: Pragmatic nonrandomised controlled trial set in 5 healthcare centres and one physiotherapy centre in PC. Fifty-three women with FM (2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia) were studied, 35 in the intervention group (IG) and 18 in the control group (CG). The women in the IG were interviewed individually and then received 6 weekly sessions plus one review session (1 month later): those in the CG received their TAU. The subject assignation to the CG or the IG was determined according to their availability to attend the sessions. They all filled in several questionnaires (prior to and 1 year after the intervention) to evaluate the impact of FM in their daily lives, catastrophism, anxiety and depression, severity and impact of pain in daily personal performance and functional capacity., Results: The reductions (improvements) in the scores of all tests (baseline-final) were greater in the IG (p < 0.05) when adjusted for age and baseline values, with moderate or high effect size. After 1 year, 20% (CI - 1 to 42%) more women in the IG, compared to the CG, had a FIQ score < 39 (mild functional impairment). 17/38 (49%) women in the IG no longer met FM criteria at the end of follow-up., Conclusions: An intervention based on PNE and exercise in patients with FM is feasible and seems effective in PC., Trial Registration: The study was retrospectively registered at ClinicalTrials.gov (Trial Registration NCT04539171 ), on 04/09/2020., (© 2022. The Author(s).)

Background: Alcohol use disorders (AUDs) are common in men who have sex with men (MSM) and transgender women (TGW) in Peru and undermine antiretroviral therapy (ART) adherence. Oral naltrexone (NTX) is an evidence-based treatment for AUD that has not been assessed in cotreating AUD in MSM/TGW with HIV., Setting and Design: A multi-site, randomized, double-blind, placebo-controlled trial among MSM/TGW with AUD and newly diagnosed with HIV in Lima, Peru., Methods: Newly diagnosed MSM/TGW with HIV and AUD were prescribed a single-treatment regimen of EFV/TDF/FTC from 2014 to 2015 and randomized 2:1 to oral NTX (N = 103) or placebo (N = 53) for 24 weeks. The primary and secondary outcomes were proportion achieving viral suppression (VS: HIV-1 RNA < 400 copies/mL) or maximal viral suppression (MVS: HIV-1 RNA < 40 copies/mL) at 24 weeks., Results: There were no significant differences between the arms in VS (81.6% NTX arm vs 75.5% placebo arm; P = 0.37) or MVS (61.2% NTX arm vs 66.0% placebo arm; P = 0.48). Adherence to study medication was low (mean = 34.6%) overall with only 21.4% of participants meeting recommended adherence levels (≥80% daily doses/month). Participants allocated to NTX had significantly lower adherence compared with placebo for both the first and second 12-week study periods, respectively (44.0% vs 35.2%, P = 0.04; 31.4% vs 35.2%, P = 0.03)., Conclusions: Findings are inconclusive regarding the use of NTX for treatment of AUD in MSM/TGW newly diagnosed with HIV. VS and MVS levels were high irrespective of allocation. Adherence to study medication was low, requiring further exploration of strategies to optimize adherence to NTX as AUD treatment., Competing Interests: F.L.A., Speakers Bureau: Gilead Sciences, Merck Pharmaceuticals, Simply Speaking HIV (SSHIV), Clinical Care Options (CCO). Advisory Board: Gilead Sciences, Merck Pharmaceuticals, and AbbVie. Grants were awarded to Yale University where he is named Principal Investigator: NIH, NIDA, NIH Fogarty International Center, HRSA, SAMHSA, Merck Clinical Trials, Gilead Foundation, Gilead Sciences, and International Association of Providers of AIDS Care (IAPAC). The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Group 2 innate lymphoid cells (ILC2s) are involved in type 2 immune responses in mucosal organs and are associated with various allergic diseases in humans. Studies are needed to understand the molecules and pathways that control ILC2s., Objective: The aims of this study were to develop a mouse model that limits the innate type 2 immune response in the lung and to investigate the immunologic mechanisms involved in regulation of lung ILC2s., Methods: Naive BALB/c mice were administered various Toll-like receptor agonists and exposed intranasally to the fungal allergen Alternaria alternata. The mechanisms were investigated using gene knockout mice as well as cultures of lung cells and isolated lung ILC2s., Results: Polyinosinic-polycytidylic acid, or poly (I:C), effectively inhibited innate type 2 response to A alternata. Poly (I:C) promoted production of IFNα, -β, and -γ, and its inhibitory effects were dependent on the IFN-α/β receptor pathway. IFN-β was 100 times more potent than IFN-α at inhibiting type 2 cytokine production by lung ILC2s. Signal transducer and activator of transcription 5 (STAT5)-activating cytokines, including IL-2, IL-7, and thymic stromal lymphopoietin, but not IL-33, promoted survival and proliferation of lung ILC2s in vitro, while IFN-β blocked these effects. Expression of the transcription factor GATA3, which is critical for differentiation and maintenance of ILC2s, was inhibited by IFN-β., Conclusions: IFN-β blocks the effects of STAT5-activating cytokines on lung ILC2s and inhibits their survival and effector functions. Administration of IFN-β may provide a new strategy to treat diseases involving ILC2s., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex-dependent manner. Notably, signaling in the adult Drosophila BBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor Hr46/Hr3 was identified as a male-enriched BBB transcript. Hr46/Hr3 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that Hr46/Hr3 is specifically required in the BBB cells for courtship behavior in mature males. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor Hr46/Hr3 in the regulation of male courtship, a novel function that is independent of its developmental role., Competing Interests: The authors have declared that no competing interests exist.

Background: Despite the impact that the SARS-CoV-2 virus infection has presented in Spain, data on the diagnostic capacity of the symptoms associated with this infection are limited, especially among patients with mild symptoms and who are detected in the primary care field (PC). The objective of the present study was to know the associated symptoms and their predictive criterial validity in SARS-CoV-2 infection among professionals working in PC., Methods: A cross-sectional, multicenter study was carried out in the Spanish National Health System, through an epidemiological survey directed to patients who underwent the PCR test for SARS-CoV-2 in the PC setting., Results: A total of 1612 patients participated, of which 86.6% were PC healthcare professionals, and of these, 67.4% family doctors. Hyposmia, with a sensitivity of 42.69% (95% CI: 37.30-48.08) and a specificity of 95.91% (95% CI: 94.78-97.03), and ageusia with a sensitivity of 39.47% (34.15-44.80) and a specificity of 95.20% (93.98-96.41) were the symptoms with the highest criteria validity indexes., Conclusions: This study identifies the specific symptoms of loss of smell or taste as the most frequently associated with SARS-CoV-2 infection, essential in the detection of COVID-19 given its high frequency and predictive capacity.

Parkinson's disease (PD) is a complex, multisystem disorder characterised by α-synuclein (SNCA) pathology, degeneration of nigrostriatal dopaminergic neurons, multifactorial pathogenetic mechanisms and expression of a plethora of motor and non-motor symptoms. Animal models of PD have already been instructive in helping us unravel some of these aspects. However, much remains to be discovered, requiring continued interrogation by the research community. In contrast with the situation for many neurological disorders, PD benefits from of a wide range of available animal models (pharmacological, toxin, genetic and α-synuclein) but this makes selection of the optimal one for a given study difficult. This is especially so when a study demands a model that displays a specific combination of features. While many excellent reviews of animal models already exist, this review takes a different approach with the intention of more readily informing this decision-making process. We have considered each feature of PD in turn - aetiology, pathology, pathogenesis, motor dysfunctions and non-motor symptoms (NMS) - highlighting those animal models that replicate each. By compiling easily accessible tables and a summary figure, we aim to provide the reader with a simple, go-to resource for selecting the optimal animal model of PD to suit their research needs., Competing Interests: The authors declare that there are no competing interests associated with the manuscript., (© 2021 The Author(s).)

After antigenic activation, quiescent naive CD4 + T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty acids, and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation of murine peripheral CD4 + T cells. HDAC3-deficient CD4 + T cells failed to proliferate and blast after in vitro TCR/CD28 stimulation. Upon T-cell activation, genes involved in cholesterol biosynthesis are upregulated while genes that promote cholesterol efflux are repressed. HDAC3-deficient CD4 + T cells had reduced levels of cellular cholesterol both before and after activation. HDAC3-deficient cells upregulate cholesterol synthesis appropriately after activation, but fail to repress cholesterol efflux; notably, they overexpress cholesterol efflux transporters ABCA1 and ABCG1. Repression of these genes is the primary function for HDAC3 in peripheral CD4 + T cells, as addition of exogenous cholesterol restored proliferative capacity. Collectively, these findings demonstrate HDAC3 is essential during CD4 + T-cell activation to repress cholesterol efflux., Competing Interests: DW, RP, JL, MK, MS, SM, MK, MR, HZ, VS No competing interests declared, (© 2021, Wilfahrt et al.)

Background and Objective: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care., Patients and Methods: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated., Results: Of 1038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2)., Conclusions: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases., (© 2021 Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care., Patients and Methods: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated., Results: Of 1,038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2)., Conclusions: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate the impact of two calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant., Background: People taking CGRP-targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small-molecule CGRP receptor antagonist, for acute treatment of breakthrough migraine attacks., Design: In this two-arm, multicenter, open-label, phase 1b trial, adults with migraine were randomized to arm 1 (ubrogepant ± erenumab) or arm 2 (ubrogepant ± galcanezumab). The PK profile of ubrogepant was characterized for administration before and 4 days after CGRP-targeted mAb injection. Participants received single-dose ubrogepant 100 mg on day 1, subcutaneous erenumab 140 mg (arm 1) or galcanezumab 240 mg (arm 2) on day 8, and ubrogepant 100 mg once daily on days 12-15. In each study arm, serial blood samples were drawn on days 1 and 12 for measurement of plasma ubrogepant concentrations. The primary outcomes were area under the plasma ubrogepant concentration-time curve (AUC) from time 0 to t post-dose (AUC 0- t ) and from time 0 to infinity (AUC 0-inf ), and maximum plasma concentration (C max ) of ubrogepant when ubrogepant was administered before or after a single dose of erenumab or galcanezumab. Vital signs and laboratory parameters were monitored., Results: Forty participants enrolled (20 per arm; mean [standard deviation] ages, 32.2 [8.9] and 38.4 [8.8] years; 50% [10/20] and 60% [12/20] female in arms 1 and 2, respectively). There were no significant differences in ubrogepant C max after versus before erenumab administration (geometric least-squares mean [LSM] ratio, 1.04 [90% CI, 0.93-1.16]), and no significant differences in AUC 0- t (1.06 [0.96-1.16]) or AUC 0-inf (1.05 [0.96-1.15]). Similarly, ubrogepant C max (1.00 [90% CI, 0.82-1.20]), AUC 0- t (1.05 [0.90-1.23]), and AUC 0-inf (1.05 [0.90-1.22]) geometric LSM ratios were statistically equivalent after galcanezumab versus ubrogepant alone. Treatment-emergent adverse events (TEAEs) were similar to those reported with each treatment alone. No serious TEAEs, TEAEs leading to discontinuation, or clinically relevant changes in laboratory parameters or vital signs were reported., Conclusions: The PK profile of ubrogepant was not significantly changed and no safety concerns were identified when ubrogepant was coadministered with erenumab or galcanezumab., (© 2021 AbbVie. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objectives: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials., Methods: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ 2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy., Results: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences., Conclusion: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT., (© 2020 British HIV Association.)

Objective: To identify the sociodemographic, clinical and epidemiological characteristics associated with the presence of infection by the SARS-CoV-2 virus in family physicians who carry out their work in Primary Care (PC) or in Hospital Emergencies., Desing: Observational analytical case-control study. SITE: Primary care., Participants: 969 Primare Care Physicians, Hospital Emergency physicians and other extrahospitalry centers that had PCR for the detection of the SARS-CoV-2. Of these, 133 participated as cases (PCR positive) and 836 as controls (PCR negative)., Interventions: No., Main Measurements: Sociodemographic and work, contact with a COVID-19 patient, symptoms present during the process, first manifested symptom, previous chronic pathologies, and tobacco use., Results: 13.7% (95% CI: 11.6-16.0) were cases infected with SARS-CoV-2. The most frequently declared symptoms by those infected were a feeling of fatigue/tiredness (69.2%; 95% CI: 60.9-77.4%), cough (56.4%; 95% CI: 47.6-65.2%) and headache (55.6%; 95% CI: 46.8-64.4%).Using logistic regression, the variables independently associated with SARS-CoV-2 virus infection in Family Physicians were: previous contact with a COVID-19 patient (OR: 2.3; 95% CI: 1.2-4.2), present fatigue / tiredness (OR: 2.2; 95% CI: 1.2-3.9), smell alteration (4.6; 95% CI: 1.7-12.5), taste alteration (OR: 32.0; 95% CI: 9.6-106.8), cough (OR: 3.0; 95% CI: 1.7-5.3) and fever (OR: 6.1; 95% CI: 3.2-11.4)., Conclusions: Symptoms independently related to SARS-CoV-2 virus infection in Family Physicians were fatigue, fever, cough, and altered taste and smell. The presence of these symptoms could facilitate the diagnosis of suspected COVID-19 disease and the earlier selection of those that require confirmatory tests., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Background: Virus neutralization by antibodies is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal murine leukemia virus genome encoding firefly luciferase. This assay design is intended for use in laboratories with biocontainment level 2 and therefore circumvents the need for the biocontainment level 3 that would be required for replication-competent SARS-CoV-2 virus. To validate the pseudovirion assay, we set up comparisons with other available antibody tests including those from Abbott, Euroimmun and Siemens, using archived, known samples., Results: 11 out of 12 SARS-CoV-2-infected patient serum samples showed neutralizing activity against SARS-CoV-2-spike pseudotyped MLV viruses, with neutralizing titers-50 (NT 50 ) that ranged from 1:25 to 1:1,417. Five historical samples from patients hospitalized for severe influenza infection in 2016 tested negative in the neutralization assay (NT 50  < 25). Three serum samples with high neutralizing activity against SARS-CoV-2/MLV pseudoviruses showed no detectable neutralizing activity (NT 50  < 25) against SARS-CoV-1/MLV pseudovirions. We also compared the semiquantitative Siemens SARS-CoV-2 IgG test, which measures binding of IgG to recombinantly expressed receptor binding domain of SARS-CoV-2 spike glycoprotein with the neutralization titers obtained in the pseudovirion assay and the results show high concordance between the two tests (R 2  = 0.9344)., Conclusions: SARS-CoV-2 spike/MLV pseudovirions provide a practical means of assessing neutralizing activity of antibodies in serum or plasma from infected patients under laboratory conditions consistent with biocontainment level 2. This assay offers promise also in evaluating immunogenicity of spike glycoprotein-based candidate vaccines in the near future.

Objective: To evaluate the effectiveness of a group intervention in Primary Care in patients with fibromyalgia (FM) based on pain neuroscience education (PNE)., Design: Pre-post study., Location: Urban Primary Health Centre in Bilbao., Participants: Patients with FM (2010 American College of Rheumatology Diagnostic Criteria for fibromyalgia), ≥18 years., Intervention: 5 weekly sessions (2hours each), and a reminder session one month later., Main Measurements: Compliance with FM criteria, assessed using the WPI (Widespread Pain Index, number of pain areas) and the SS (severity of symptoms) questionnaires. An assessment was also made on the impact of FM on functional capacity (FIQ:≥20% and ≥50% reduction in the FIQ total score from baseline to after treatment, and proportion of patients with FIQ<39 at the end of the study). Assessments were made at baseline, one month following the 5th session, and during the 6- and 12-month follow-up., Results: All the study evaluations were completed by 85/98 patients. A statistically significant improvement was observed in the 3 studied categories (WPI, SS, and FIQ) since the first visit, and was maintained until the final visit (12 months later). A total of 45 patients (53%, 95% CI: 42%-63%), more than those at baseline, scored FIQ<39 (no worse than mild functional impairment). One month following the 5th session there were 44 patients (52%, 95% CI: 41%-62%) that no longer met FM criteria and, at the end of follow-up, there were 56 patients (66%, 95% CI: 55%-75%)., Conclusions: An intervention based on PNE has shown to be feasible in Primary Care, with results in the upper range of those published with other treatments for FM., (Copyright © 2019 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To analyze the situation, evaluation and proposals for improvement of the Preventive Activities and Health Promotion Program (PAPPS)., Material and Methods: A qualitative study of situation analysis was carried out for the evaluation of the PAPPS in 2 phases: 1) Generation of ideas and collection of information through a DAFO matrix, using 2 types of criteria: internal (strengths and weaknesses), and external (threats and opportunities); 2) Prioritization of the improvement proposals collected. Selection of participants: Key informants were identified taking into account their relationship and knowledge of the PAPPS program. All members of the PAPPS, expert groups and members with past participation were included, as well as the coordinators, including the autonomous leaders of the PAPPS. Two invitations to participate in the study were sent: the first from December 29, 2017 to February 11, 2018, and the second from January 10 to 23, 2019. The information was obtained from a questionnaire designed to be self-completed., Results and Conclusions: A total of 73 subjects answered the questionnaire. 35% of the participants were members of the PAPPS working groups, followed by family doctors from other areas, with 20.5%. The order of prioritization of the improvement proposals was as follows: 1) Unify recommendations with other semFYC working groups; 2) Prepare lists with "Recommendations not to do" from the point of view of prevention; 3) Incorporate PAPPS in the political agenda; 4) Greater coordination and interaction between groups with common competences; 5) Teaching in undergraduate and teaching units; 6) Review, update and dissemination of the program in Primary Care., (Copyright © 2020 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19.

Objective: The identification of atrial fibrillation in older patients who come to Primary Care consultations is a topic of interest that has been scarcely studied. The objective of this work was to estimate the frequency of new cases of atrial fibrillation and to analyze the clinical-epidemiological characteristics of patients 65 years of age or older, detected in Primary Care in Spain., Methods: An observational, descriptive, national, multicenter study was carried out in 48 health centers, in which 218 doctors and 101 Primary Care nurses recruited 7,068 patients, who underwent an arterial pulse and an electrocardiogram. in case of being abnormal or doubtful, determining the presence of atrial fibrillation and other rhythm disorders, symptoms and signs compatible with atrial fibrillation and comorbidity and cardiovascular risk factors. A univariate, bivariate and multivariate analysis (multiple logistic regression) was performed., Results: The patients had a mean age of 74.41±6.78 (DT) years. 2.3% presented atrial fibrilation (95% CI: 2.0-2.7), being its frequency higher in men (2.9%; p<0.001), and as age increased (p<0.001). The most frequent symptoms present among patients with atrial fibrillation were palpitations (Odds Ratio -OR-=3.50; 95% CI: 2.28-5.37), dyspnea (OR=2.71; 95% CI: 1.87-3.90), general discomfort (OR=2.32, 95% CI: 1.15-4.63), and dizziness (OR=1.80, 95% CI: 1.20-3.51). The 21.8% were asymptomatic., Conclusions: The frequency of new cases of atrial fibrillation in the Spanish population of 65 years or older is high, being higher in men and increasing with age. Two out of ten patients are asymptomatic. Palpitations and dyspnea are the predominant symptoms in patients with atrial fibrillation.

Transposable elements (TEs) are mobile genetic parasites that spread through host genomes by replicating in germline cells. New TE copies that arise in the genomes of germline stem cells (GSCs) are of particular value, because they are potentially transmitted to multiple offspring through the plethora of gametes arising from the same progenitor GSC. However, the fidelity of GSC genomes is also of utmost importance to the host in ensuring the production of abundant and fit offspring. Here we review tactics that TEs employ to replicate in Drosophila female GSCs, as well as mechanisms those cells use to defend against TEs. We also discuss the relationship between transposition and GSC loss, which is arbitrated through reduced signaling for self renewal, increased signaling for differentiation, and DNA damage response pathways., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Understanding social network structures can contribute to the introduction of new HIV prevention strategies with socially marginalized populations like transgender women (TW). We conducted 20 semi-structured interviews and four focus groups (n = 32) with TW from selected social networks in Lima, Peru between May and July, 2015. Participants described layers of social influence from diverse actors in their social networks. The majority identified a close relative as their primary social support, with whom they confided secrets but avoided issues of transgender identity, sexuality, and sex work. Participants described close circles of TW friends with whom they shared information about gender identity, body modification, and sexual partners, but avoided issues like HIV. Community leadership included political leaders (who advocated for transgender rights) as well as social leaders (who introduced TW to hormone therapy, body modification, and commercial sex). Detailed analysis of TW social networks can contribute to implementation and acceptability of new HIV prevention technologies.

Objectives: To assess meningitis treatment in Lebanon's compatibility with the Infectious Diseases Society of America (IDSA) guidelines and the effect of non-compliance on mortality. Methods: This is a retrospective study, conducted in 5 Lebanese hospitals, and enrolling all patients diagnosed with meningitis who presented to the involved hospitals from January 2008 to December 2016.  Results: A total of 252 participants were enrolled in the study. Of these patients, 205 (82.7%) were diagnosed with viral meningitis and 47 (17.3%) with bacterial meningitis, which was confirmed using laboratory tests. For patients with viral meningitis, 128 (62.4%) remained on the initial prescribed antibiotics despite the negative cerebrospinal fluid (CSF) and blood culture results. For bacterial meningitis patients, 30.8% received treatment regimen incompatible with the IDSA guidelines. The most common reason for the treatment incompatibility was the definitive drug choice after the culture results (49.1%) and the least common reason was inappropriate hospital stay days (25.9%). The mortality rate was 13.5%. Having low proteins values in the CSF (odds ratio=0.095) was associated with lower mortality compared to patients with normal protein values. Conclusion: This study shows a high percentage of inappropriate treatment in Lebanese hospitals despite these hospitals having adopted international treatment guidelines. This inappropriate management was associated with an increasing rate of mortality and neurological complications.

Headache in patients with calcified neurocysticercosis (NCC) is probably common but has been largely overlooked. We aimed to assess the presence, characteristics, and diagnosis of headache across patients with calcified NCC and their matched controls. In this case-control study nested to a population-based cohort, Atahualpa residents aged ≥ 20 years with calcified NCC were identified as case patients and paired 1:1 to age- and gender-matched randomly selected controls. A culturally adapted questionnaire was derived from the EUROLIGHT. Headache diagnosis was established according to the International Classification of Headache Disorders, 3rd edition. Conditional logistic regression models for matched paired data were fitted to assess the independent association between calcified NCC (as the exposure) and headache variables, after adjusting for education, alcohol intake, depression, and epilepsy. The selection process generated 106 case patients and their matched controls. Lifetime headache prevalence (odds ratio [OR]: 4.18; 95% Confidence Interval [CI]: 1.79-9.75; P = 0.001), current headaches (OR: 4.19; 95% CI: 1.92-9.16; P < 0.001), and intense headaches (OR: 9.47; 95% CI: 2.88-31.19; P < 0.001) were more frequent among cases than in controls. In addition, migraine (but not other forms of headache) was more frequent among subjects with calcified NCC (OR: 4.89; 95% CI: 2.36-11.39; P < 0.001). This study shows a robust epidemiological association between headache-particularly migraine-and calcified NCC.

Setting: A safe, effective vaccine would improve tuberculosis (TB) control worldwide. Extensive community engagement will be essential to ensure the interest and participation of populations at highest risk., Objective/method: To inform the potential implementation of efficacy studies, we assessed TB knowledge, attitudes towards licensed vaccines and willingness to participate in future TB vaccine efficacy trials among 262 household contacts of 79 recently diagnosed pulmonary TB cases in Lima, Peru., Results: Overall knowledge of TB was low. Only 41.6% of household contacts perceived themselves as being at high risk of acquiring TB. Slightly above half (54.2%) indicated willingness to participate in a TB vaccine trial. After clustered analysis adjusting for homogeneity among families, willingness to enroll was associated with belief that receiving all recommended vaccinations is important (adjusted OR [aOR] 3.28, P = 0.016), desire to know more about TB risk factors and clinical trials (aOR 2.60, P = 0.004), older age (aOR 1.02, P = 0.027) and TB knowledge (aOR 0.05, P = 0.039)., Conclusion: Barriers to participation in TB vaccine trials exist among individuals at high risk for TB. Targeted education about TB risk factors, TB transmission and education about the clinical trial process will be critical for laying the groundwork for future vaccine trials.

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.