Interest in event-driven PrEP among men who have sex with men using daily PrEP in Mexico in 2019-2020: a cross-sectional assessment in a large-scale demonstration project.

This study aimed to evaluate the interest in event-driven PrEP (ED-PrEP) among men who have sex with men (MSM) using daily PrEP in Mexico's PrEP demonstration project between 2019 and 2020. We compared participants interested or not in ED-PrEP during their first-month visit and identified associated factors. Of 1,021 MSM attending their first-month visit, 7% had previous knowledge of ED-PrEP, but 40% were interested in ED-PrEP. However, over 50% perceived the scheme as less protective than daily PrEP. Having doubts about ED-PrEP's level of protection was related to less interest in the scheme (aOR = 0.11; CI = 0.07-0.18), just like reporting perceived barriers such as having frequent sex (aOR = 0.06; CI = 0.03-0.14), unplanned sex (aOR = 0.17; CI = 0.11-0.27), forgetting the medicine (aOR = 0.06; CI = 0.03-0.12), or difficulty carrying the medicine (aOR = 0.13; CI = 0.07-0.25). Finally, reporting not taking PrEP for >20 days in the last month (aOR = 0.05; CI = 0.01-0.27) diminished interest in ED-PrEP. In conclusion, few MSM daily PrEP users knew about ED-PrEP yet many were interested in it, suggesting the importance of awareness campaigns regarding ED-PrEP's effectiveness. The lack of interest in ED-PrEP among participants with poor adherence to daily PrEP indicates that they might prefer long-acting PrEP or HIV prevention strategies without medication.

Comparative effectiveness of frame-based and mask-based Gamma Knife stereotactic radiosurgery in brain metastases: A 509 patient meta-analysis.

PURPOSE: Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. METHODS: Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. RESULTS: From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89-1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78-0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89-1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72-3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38-21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22-1.76, p = 0.37). CONCLUSION: Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions.

Eugenia pohliana leaves essential oil inhibits fungal virulence and restores antibiotic efficacy in multidrug-resistant bacterial strains.

This study aims to investigate the essential oil from leaves of E. pohliana (EOEP) in regard to its chemical composition, antimicrobial and drug-enhancing activity, as well as the reduction of fungal virulence capacity. Chemical characterization using GC-MS showed as major components the sesquiterpenes δ-cadinene, Epi-α-Muurolol, and bicyclogermacrene. The results of antibacterial tests indicated that Staphylococcus aureus was more sensitive to EOEP, that also enhanced the efficacy of gentamicin, erythromycin, and norfloxacin. EOEP exhibited antifungal properties against Candida albicans, in addition to potentiating the effectiveness of fluconazole against Candida tropicalis. It showed anti-virulence effects in all fungal strains. These findings underscore Eugenia pohliana as a potential candidate for the prospection of novel therapeutic agents to treat infectious diseases caused by resistant microbes.

Age-associated clonal B cells drive B cell lymphoma in mice.

Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention.

Population-level trends in self-reported healthcare utilization among older adults in Mexico with and without cognitive impairment.

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. RESULTS: For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03-1.23) but lower risk of outpatient services (RR = 0.95, 0.93-0.97), cholesterol screening (RR = 0.93, 0.91-0.96), and diabetes screening (RR = 0.95, 0.92-0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. CONCLUSIONS: We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

Bottom-up Synthesis and Characterization of Porous 12-Atom-Wide Armchair Graphene Nanoribbons.

Although several porous carbon/graphene nanoribbons (GNRs) have been prepared, a direct comparison of the electronic properties between a nonporous GNR and its periodically perforated counterpart is still missing. Here, we report the synthesis of porous 12-atom-wide armchair-edged GNRs from a bromoarene precursor on a Au(111) surface via hierarchical Ullmann and dehydrogenative coupling. The selective formation of porous 12-GNRs was achieved through thermodynamic and kinetic reaction control combined with tailored precursor design. The structure and electronic properties of the porous 12-GNR were elucidated by scanning tunneling microscopy/spectroscopy and density functional theory calculations, revealing that the pores induce a 2.17 eV band gap increase compared to the nonporous 12-AGNR on the same surface.

Determination of the frequency of individuals with broadly cross-reactive neutralizing antibodies against PRRSV in the sow population under field conditions.

BACKGROUND: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant swine pathogen, yet the immune response components contributing to protection remain incompletely understood. Broadly reactive neutralizing antibodies (bNAs) may play a crucial role in preventing reinfections by heterologous viruses, although their occurrence is considered low under both field and experimental conditions. This study aimed to assess the frequency of sows exhibiting bNAs against PRRSV under field conditions and to analyze the epidemiological factors influencing the occurrence of these elite neutralizers. Blood samples were collected from breeding sows across eleven unrelated pig farms, with samples categorized by parity. Serum obtained was utilized in virus neutralization assays (VNs) against six PRRSV field isolates and two MLV strains. RESULTS: Approximately 7% of the sows exhibited neutralization activity against all viruses in the panel, with a geometric mean of the titer (GMT) of NAs at or exceeding 4 log2. Exclusion of the PRRSV-2 isolate from the panel increased the proportion of elite neutralizers to around 15%. Farm-specific analysis revealed significant variations in both GMT of NAs and proportion of elite neutralizers. PRRSV unstable farms and those with a PRRS outbreak in the last 12 months displayed higher GMT of NAs compared to stable farms without recent outbreaks. The GMT of NAs showed a gradual, albeit moderate, increase with the parity of the sows. Parity's impact on bNA response was consistently observed in stable farms but not necessarily in unstable farms or those with recent outbreaks. Finally, the results indicated that vaccinated animals had higher NA titers against the vaccine virus used in the farm than against field viruses. CONCLUSION: bNAs against heterologous isolates induced by PRRSV infection under field conditions are generally low, often falling below titers necessary for protection against reproductive failure. However, a subset of sows (approximately 15%) can be considered elite neutralizers, efficiently recognizing various PRRSV strains. Repeated exposures to PRRSV play a crucial role in eliciting these bNAs, with a higher frequency observed in unstable farms and those with recent outbreaks. In stable farms, parity only marginally influences bNA titers, highlighting its limited role compared to the impact of PRRSV exposure history.

Early feeding practices and eating behaviour in preschool children: The CORALS cohort.

This study aimed to investigate if the duration of breastfeeding and the method at initiation of complementary feeding affect eating behaviour in children aged 3-6 years. This is a cross-sectional analysis from the Childhood Obesity Risk Assessment Longitudinal Study project, an ongoing longitudinal cohort study that aims to identify childhood obesity risk factors in Spanish children. A total of 1215 children aged 3-6 years were included. Breastfeeding duration and the method of initiation of complementary feeding [baby-led weaning (BLW), traditional/spoon or mixed method] were evaluated. Eating behaviour at 3-6 years was assessed with the Child Eating Behaviour Questionnaire. Generalized linear models were fitted to assess the association between the aforementioned exposures and eating behaviour. Children breastfed for ≥4 months were less likely to be fussy eaters at 3-6 years compared to those breastfed for <1 month (OR: 0.86 95% CI: 0.76-0.98; p = 0.031). Compared to those children using the traditional/spoon-feeding method, those initiating complementary feeding through BLW or through a mixed approach were more likely to have higher scores on the enjoyment of food (EF) (OR, 95% CI: 1.33, 1.13-1.57; p = 0.001 and 1.17, 1.05-1.30; p = 0.002, respectively) and lower scores on food fussiness (FF) at 3-6 years (0.76, 0.62-0.91; p = 0.004 and 0.87, 0.78-0.98; p = 0.033, respectively). Breastfeeding for ≥4 months and initiation of complementary feeding with the BLW and a mixed approach were associated with greater EF and lower FF, which should endure practice.

Enhancing the First-Pass Effect in Acute Stroke: The Impact of Stent Retriever Characteristics.

Introduction: Although stentrievers (SRs) have been a mainstay of mechanical thrombectomy (MT), and current guidelines recommend the use of SRs in the treatment of large vessel occlusion stroke (LVO), there is a paucity of studies in the literature comparing SRs directly against each other in terms of mechanical and functional properties. Timely access to endovascular therapy and the ability to restore intracranial flow in a safe, efficient, and efficacious manner have been critical to the success of MT. This study aimed to investigate the impact of contemporary SR characteristics, including model, brand, size, and length, on the first-pass effect (FPE) in patients with acute ischemic stroke. Methods: Consecutive patients with M1 occlusion treated with a single SR+BGC were recruited from the ROSSETTI registry. The primary outcome was the FPE that was defined as modified (mFPE) or true (tFPE) for the achievement of modified thrombolysis in cerebral infarction (mTICI) grades 2b-3 or 3 after a single device pass, respectively. We compared patients who achieved mFPE with those who achieved tFPE according to SR characteristics. Results: We included 610 patients (52.3% female and 47.7% male, mean age 75.1 ± 13.62 years). mFPE was achieved in 357 patients (58.5%), whereas tFPE was achieved in 264 (43.3%). There was no significant association between SR characteristics and mFPE or tFPE. Specifically, the SR size did not show a statistically significant relationship with improvement in FPE. Similarly, the length of the SR did not yield significant differences in the mFPE and tFPE, even when the data were grouped. Conclusions: Our data indicate that contemporary SR-mediated thrombectomy characteristics, including model, brand, size, and length, do not significantly affect the FPE.

Assessing the impact of long-term inhaled corticosteroid therapy on patients with COVID-19 and coexisting chronic lung disease: A multicenter retrospective cohort study.

Background: Patients with chronic lung disease (CLD), such as asthma or chronic obstructive pulmonary disease, were expected to have an increased risk of clinical manifestations and severity of COVID-19. However, these comorbidities have been reported less frequently than expected. Chronic treatment with inhaled corticosteroids (ICS) may impact the clinical course of COVID-19. The main objective of this study is to know the influence of chronic treatment with ICS on the prognosis of COVID-19 hospitalized patients with CLD. Methods: A multicenter retrospective cohort study was designed, including patients hospitalized with COVID-19. Epidemiological and clinical data were collected at admission and at seven days, and clinical outcomes were collected. Patients with CLD with and without chronic treatment with ICS were compared. Results: Two thousand five hundred ninety-eight patients were included, of which 1,171 patients had a diagnosis of asthma and 1,427 of COPD (53.37% and 41.41% with ICS, respectively). No differences were found in mortality, transfer to ICU, or development of moderate-severe ARDS. Patients with chronic ICS had a longer hospital stay in both asthma and COPD patients (9 vs. 8 days, p = 0.031 in asthma patients), (11 vs. 9 days, p = 0.018 in COPD patients); although they also had more comorbidity burden. Conclusions: Patients with chronic inhaled corticosteroids had longer hospital stays and more chronic comorbidities, measured by the Charlson comorbidity index, but they did not have more severe disease at admission, evaluated with qSOFA and PSI scores. Chronic treatment with inhaled corticosteroids had no influence on the prognosis of patients with chronic lung disease and COVID-19.

Ultraprocessed Food Consumption and Cardiometabolic Risk Factors in Children.

Importance: High intake of ultraprocessed foods (UPFs) has been associated with higher cardiometabolic risk in adults; however, the evidence in children is limited. Objective: To investigate the association between UPF consumption and cardiometabolic risk factors in the Childhood Obesity Risk Assessment Longitudinal Study (CORALS). Design, Setting, and Participants: This baseline cross-sectional analysis was conducted using the data of CORALS participants recruited between March 22, 2019, and June 30, 2022. Preschool children (aged 3-6 years) were recruited from schools and centers in 7 cities in Spain. Inclusion criteria included informed consent signed by parents or caregivers and having a completed a set of questionnaires about the child's prenatal history at home. Exclusion criteria included low command of Spanish or unstable residence. Exposure: Energy-adjusted UPF consumption (in grams per day) from food frequency questionnaires and based on the NOVA food classification system. Main Outcomes and Measures: Age- and sex-specific z scores of adiposity parameters (body mass index [BMI], fat mass index, waist-to-height ratio, and waist circumference) and cardiometabolic parameters (diastolic and systolic blood pressure, fasting plasma glucose, homeostasis model assessment for insulin resistance, high-density and low-density lipoprotein cholesterol, and triglycerides) were estimated using linear regression models. Results: Of 1509 enrolled CORALS participants, 1426 (mean [SD] age, 5.8 [1.1] years; 698 boys [49.0%]) were included in this study. Mothers of children with high UPF consumption were younger, had a higher BMI, were more likely to have overweight or obesity, and had lower education levels and employment rates. Compared with participants in the lowest tertile of energy-adjusted UPF consumption, those in the highest tertile showed higher z scores of BMI (ß coefficient, 0.20; 95% CI, 0.05-0.35), waist circumference (ß coefficient, 0.20; 95% CI, 0.05-0.35), fat mass index (ß coefficient, 0.17; 95% CI, 0.00-0.32), and fasting plasma glucose (ß coefficient, 0.22; 95% CI, 0.06-0.37) and lower z scores for HDL cholesterol (ß coefficient, -0.19; 95% CI, -0.36 to -0.02). One-SD increments in energy-adjusted UPF consumption were associated with higher z scores for BMI (ß coefficient, 0.11; 95% CI, 0.05-0.17), waist circumference (ß coefficient, 0.09; 95% CI, 0.02-0.15), fat mass index (ß coefficient, 0.11; 95% CI, 0.04-1.18), and fasting plasma glucose (ß coefficient, 0.10; 95% CI, 0.03-0.17) and lower HDL cholesterol (ß coefficient, -0.07; 95% CI, -0.15 to -0.00). Substituting 100 g of UPFs with 100 g of unprocessed or minimally processed foods was associated with lower z scores of BMI (ß coefficient, -0.03; 95% CI, -0.06 to -0.01), fat mass index (ß coefficient, -0.03; 95% CI, -0.06 to 0.00), and fasting plasma glucose (ß coefficient, -0.04; 95% CI, -0.07 to -0.01). Conclusions and Relevance: These findings suggest that high UPF consumption in young children is associated with adiposity and other cardiometabolic risk factors, highlighting the need for public health initiatives to promote the replacement of UPFs with unprocessed or minimally processed foods.

Real-life clinical practice in Spain in the setting of new drug availability for ITP treatment. A Delphi-based Spanish expert panel consensus.

Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.

What is the context? Immune thrombocytopenia (ITP) is a hematologic autoimmune disease characterized by accelerated destruction and inadequate production of platelets mediated by autoantibodies (platelet count <100 × 10⁹ /L).Despite being a common condition, its heterogeneous clinical course makes its diagnosis and management still a challenge.In recent years, new molecules with different mechanisms of action have emerged for the treatment of ITP.Due to the increasing information about the pathology and its therapies, several international guidelines have recently been established to provide recommendations for the management and treatment of ITP.There are still many patient scenarios and disease aspects which are not addressed in the guidelines.What is new? Our Spanish ITP Expert Group has developed a Delphi consensus study to provide recommendations and promote standardization of the management of adult patients with ITP in Spain.The scientific committee defined 127 statements for consensus, corresponding to 13 chapters: (i) Diagnosis of ITP, (ii) First-line treatment, (iii) Second-line treatment, (iv) Treatment of refractory patients, (v) Follow-up, (vi) Emergency and surgery, (vii) ITP in the elderly, (viii) ITP in pregnancy, (ix) Anticoagulation and antiplatelet, (x) Secondary ITP, (xi) Quality of life, (xii) Discontinuation of TPO-RA, and (xiii) ITP and Covid.The total number of agreed statements achieved was 103, giving a final percentage of consensus in the Delphi questionnaire of 81%.What is the impact? This Delphi consensus provides recommendations based on real clinical practice data, regarding the diagnosis, treatment, and management of patients and scenarios in ITP to assist clinicians in addressing this disease and achieving optimal outcomes for the patient.

A disease similarity approach identifies short-lived Niemann-Pick type C disease mice with accelerated brain aging as a novel mouse model for Alzheimer's disease and aging research.

Since its first description in 1906 by Dr. Alois Alzheimer, Alzheimer's disease (AD) has been the most common type of dementia. Initially thought to be caused by age-associated accumulation of plaques, in recent years, research has increasingly associated AD with lysosomal storage and metabolic disorders, and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions. However, the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined. Here, we applied a disease similarity approach to identify unknown molecular targets of AD by using transcriptomic data from congenital diseases known to increase AD risk, namely Down Syndrome, Niemann Pick Disease Type C (NPC), and Mucopolysaccharidoses I. We uncovered common pathways, hub genes, and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of AD pathology, many of which have never been associated with AD. We then investigated common molecular alterations in brain samples from an NPC disease mouse model by juxtaposing them with brain samples of both human and mouse models of AD. Detailed phenotypic and molecular analyses revealed that the NPC mut mouse model can serve as a potential short-lived in vivo model for AD research and for understanding molecular factors affecting brain aging. This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on AD research while highlighting shortcomings and lack of correlation in diverse in vitro models. Considering the lack of an AD mouse model that recapitulates the physiological hallmarks of brain aging, the characterization of a short-lived NPC mouse model will further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of AD from a perspective of accelerated brain aging.

Frailty and spatialization of older adults in the city of Uberlândia with IVCF-20.

OBJECTIVE: To describe the functional clinical profile of elderly people linked to primary health care, using the Functional Clinical Vulnerability Index (IVCF-20) and to spatialize those with the greatest functional decline by primary health care units in the municipality of Uberlândia, in the state of Minas Gerais (MG), in the year 2022. METHODS: A cross-sectional study with secondary data from the Municipal Health Department of Uberlândia-MG. The variables were compared using Student's t-test, Mann Whitney test, Pearson's chi-square, and multinomial logistic regression to obtain the independent effect of each variable. The significance level adopted was 5% (p < 0.05). The georeferenced database in ArcGIS® was used. RESULTS: 47,182 older adults were evaluated with a mean age of 70.3 years (60 to 113 years), 27,138 of whom were women (57.52%), with a clear predominance of low-risk or robust older adults (69.40%). However, 11.09% are high-risk older adults and 19.52% are at risk of frailty. Older men had independently lower odds of moderate and high risk compared to older women (OR = 0.53; p < 0.001). A high prevalence of polypharmacy was observed, 21.40% of the older adult population, particularly in frail older adults, with a prevalence of 63.08%. There was a greater distribution of frail older adults around the central region of the municipality and in health units with a larger coverage area. The IVCF-20 made it possible to screen frailty in primary health care. CONCLUSION: The instrument is capable of stratifying the risk of older adults in health care networks through primary health care, enabling the application of individualized preventive, promotional, palliative, or rehabilitative interventions, according to the clinical functional stratum of the older adult and the compromised functional domains. Risk stratification and spatial distribution of the frailest older adults can be a good strategy for qualifying health professionals with the aim of maximizing the autonomy and independence of the older adults.

Improving the ability to discriminate medical multiple-choice questions through the analysis of the competitive examination to assign residency positions in Spain.

INTRODUCTION: Psychometrics plays a vital role in evaluating educational research, including the analysis of multiple-choice exams. This study aims to improve the discriminatory ability of the "Médico Interno Residente" (MIR) medical exam in Spain, used to rank candidates for specialized healthcare training, through psychometric analysis. METHODS: We analyzed 2,890 MIR exam questions from 2009 to 2021 (totaling 147,214 exams), categorizing them based on methodology and response type. Evaluation employed classical test theory and item response theory (IRT). Classical test theory determined difficulty and discrimination indices, while IRT assessed the relationship between knowledge levels and question performance. RESULTS: Question distribution varied across categories and years. Frequently addressed knowledge areas included various medical specialties. Non-image-associated clinical cases were the easiest, while case-based clinical questions exhibited the highest discriminatory capacity, differing significantly from image-based case or negative questions. High-quality questions without images had longer stems but shorter answer choices. Adding images reduced discriminatory power and question difficulty, with image-based questions being easier. Clinical cases with images had shorter stems and longer answer choices. CONCLUSIONS: For improved exam performance, we recommend using a clinical case format followed by direct short-answer questions. Questions should be of low difficulty, providing clear and specific answers based on scientific evidence and avoiding ambiguity. Typical clinical cases with key characteristic features should be presented, excluding uncertain boundaries of medical knowledge. Questions should have lengthy stems and concise answer choices, minimizing speculation. If images are used, they should be typical, clear, consistent with the exam, and presented within clinical cases using clinical semiotics and propaedeutics.

Artificial neural networks reconstruct missing perikymata in worn teeth.

Dental evolutionary studies in hominins are key to understanding how our ancestors and close fossil relatives grew from the early stages of embryogenesis into adults. In a sense, teeth are like an airplane's 'black box' as they record important variables for assessing developmental timing, enabling comparisons within and between populations, species, and genera. The ability to discern this type of nuanced information is embedded in the nature of how tooth enamel and dentin form: incrementally and over years. This incremental growth leaves chronological indicators in the histological structure of enamel, visible on the crown surface as perikymata. These structures are used in the process of reconstructing the rate and timing of tooth formation. Unfortunately, the developmentally earliest growth lines in lateral enamel are quickly lost to wear once the tooth crown erupts. We developed a method to reconstruct these earliest, missing perilymata from worn teeth through knowledge of the later-developed, visible perikymata for all tooth types (incisors, canines, premolars, and molars) using a modern human dataset. Building on our previous research using polynomial regressions, here we describe an artificial neural networks (ANN) method. This new ANN method mostly predicts within 2 counts the number of perikymata present in each of the first three deciles of the crown height for all tooth types. Our ANN method for estimating perikymata lost through wear has two immediate benefits: more accurate values can be produced and worn teeth can be included in dental research. This tool is available on the open-source platform R within the package teethR released under GPL v3.0 license, enabling other researchers the opportunity to expand their datasets for studies of periodicity in histological growth, dental development, and evolution.

Hospital antimicrobial stewardship: profiling the oral microbiome after exposure to COVID-19 and antibiotics.

Introduction: During the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA). Methods: The saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received. Results: Our study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, with Candida albicans detected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggests Staphylococcus aureus as a potential risk factor for sepsis. Discussion: Our results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient's salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria.

Improvements in Jump Height, Speed, and Quality of Life through an 8-Week Strength Program in Male Adolescents Soccer Players.

This study aimed to assess the enhancement of physical fitness and quality of life through an 8-week strength training program in male adolescent soccer players aged between 12 and 13 years. A lower body muscle group intervention was performed, with 17 players in the experimental group (EG) and 15 players in the control group (CG). The EG carried out soccer training complemented by specific strength work. Pre- and post- intervention assessments included body composition, jump height, speed with change of direction, maximum speed in 20 m, movement velocity in back-squat, perceived fatigue effort, academic performance, and quality of life. A general linear repeated measures model analysis was used considering each variable, the interaction between groups (EG, CG) and time (basal, 8-week), to analyze the differences between and within groups. The results showed a reduction in fat in the upper limbs and trunk, improvements in jump height, maximum speed of 20 m, and changes of direction, and increased quality of life (p < 0.05) in the EG. It was concluded that a strength program could improve some components of physical performance in male adolescent soccer players.

Prognostic Value of D-dimer to Lymphocyte Ratio (DLR) in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients: A Validation Study in a National Cohort.

BACKGROUND: This study aimed to validate the role of the D-dimer to lymphocyte ratio (DLR) for mortality prediction in a large national cohort of hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: A retrospective, multicenter, observational study that included hospitalized patients due to SARS-CoV-2 infection in Spain was conducted from March 2020 to March 2022. All biomarkers and laboratory indices analyzed were measured once at admission. RESULTS: A total of 10,575 COVID-19 patients were included in this study. The mean age of participants was 66.9 (±16) years, and 58.6% (6202 patients) of them were male. The overall mortality rate was 16.3% (n = 1726 patients). Intensive care unit admission was needed in 10.5% (n = 1106 patients), non-invasive mechanical ventilation was required in 8.8% (n = 923 patients), and orotracheal intubation was required in 7.5% (789 patients). DLR presented a c-statistic of 0.69 (95% CI, 0.68-0.71) for in-hospital mortality with an optimal cut-off above 1. Multivariate analysis showed an independent association for in-hospital mortality for DLR > 1 (adjusted OR 2.09, 95% CI 1.09-4.04; p = 0.03); in the same way, survival analysis showed a higher mortality risk for DLR > 1 (HR 2.24; 95% CI 2.03-2.47; p < 0.01). Further, no other laboratory indices showed an independent association for mortality in multivariate analysis. CONCLUSIONS: This study confirmed the usefulness of DLR as a prognostic biomarker for mortality associated with SARS-CoV-2 infection, being an accessible, cost-effective, and easy-to-use biomarker in daily clinical practice.