Prevalence of sexually risky behaviors among Mexican medical students.

University students are at high risk of sexually transmitted infections due to the lack of adequate sexual education, as well as multiple associated factors, which lead to risky sexual practices. It is important to update data about sexual behaviors to identify the main factors associated with sexually risky behaviors. The present study aimed to evaluate the current prevalence of sexually risky practices in medical students. A cross-sectional study was conducted among medical students through an anonymous self-administered online questionnaire including demographic characteristics and sexual behaviors. We used descriptive statistics and multivariable regression to analyze the data collected. A total of 1520 undergraduate medical students aged between 18 and 28 years old were included in the study. Sixty percent of the students were sexually active with a higher proportion in men (70%), likewise, they had an earlier sexual debut (16.5 vs 16.9 years old), and a greater number of lifetime sexual partners than women (3.8 vs 2.2). The main sexual activity in both groups was vaginal sex with high use of condoms (75%), however, most of them (67%) reported having unprotected oral sex. Logistic regression analysis showed that condomless sex was associated with having oral sex, anal sex, and being female. The findings of this study showed that medical university students are involved in risky sexual behaviors, the major risk factor was unprotected oral sex. Based on these results, we recommended designing interventions to improve sexual education and preventive approaches from early stages such as in middle school students to mitigate sexually transmitted infections among medical university students.

Laminin Alpha 2 Enhances the Protective Effect of Exosomes on Human iPSC-Derived Cardiomyocytes in an In Vitro Ischemia-Reoxygenation Model.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.

Adaptation and Validation of the MapMe Body Image Scales in Spanish Parents of Schoolchildren.

Childhood overweight and obesity is a worldwide problem and to treat it parents' detection has to be improved. The MapMe Body Image Scales (BIS) are a visual tool developed to improve parental perception of child weight in the United Kingdon (UK) based on British growth reference criteria. The aim of this study was to make a transcultural adaptation and validation of the MapMe BIS in Spain based on International Obesity Task Force (IOTF) cut offs A descriptive cross-sectional study was done. First, a translation and cultural adaptation was carried out. A total of 155 10-11-year-old children and their parents participated in this study. Children were measured to calculate their weight status, Body Mass Index (BMI), Body Fat Percentage (BFP) and Waist Circumference (WC), and their parents completed a purpose designed questionnaire about their perception and satisfaction of child's body weight status using the adapted BIS. Test-retest reliability, criterion validity and concurrent validity of the adapted BIS were analyzed. This study shows that the adapted MapMe BIS has good psychometric properties and is a suitable visual scale to assess parental perception of weight status in 10 and 11-year-old children in Spain.

Extracellular Vesicles and Their Correlation with Inflammatory Factors in an Experimental Model of Steatotic Liver Disease Associated with Metabolic Dysfunction.

Background/Aims: Extracellular vesicles (EVs) are promising as a biomarker of metabolic dysfunction associated steatotic liver disease (MASLD). The objective is to study EVs and their involvement in MASLD concerning the disease's pathogenesis and progression characteristics. Methods: Male adult Sprague Dawley rats were randomly assigned into two experimental models of MASLD: MASLD-16 and MASLD-28, animals received a choline-deficient high-fat diet (CHFD) and Control-16 and Control-28, animals received a standard diet (SD) for 16 and 28 weeks, respectively. Biological samples from these animal models were used, as well as previously registered variables. EVs from hepatic tissue were characterized using confocal microscopy. EVs were isolated through differential ultracentrifugation from serum and characterized using NanoSight. The data from the EVs were correlated with biochemical, molecular, and histopathological parameters. Results: Liver EVs were identified through the flotillin-1 protein. EVs were isolated from the serum of all groups. There was a decrease of EVs concentration in MASLD-28 in comparison with Control-28 (P < 0.001) and a significant increase in EVs concentration in Control-28 compared with Control-16 (P < 0.001). There was a strong correlation between serum EVs concentration with hepatic gene expression of interleukin (Il)6 (r2 = 0.685, P < 0.05), Il1b (r2 = 0.697, P < 0.05) and tumor necrosis factor-alpha (Tnfa; r2 = 0.636, P < 0.05) in MASLD-16. Moreover, there was a strong correlation between serum EVs size and Il10 in MASLD-28 (r2 = 0.762, P < 0.05). Conclusion: The concentration and size of EVs correlated with inflammatory markers, suggesting their involvement in the systemic circulation, cellular communication, and development and progression of MASLD, demonstrating that EVs have the potential to serve as noninvasive biomarkers for MASLD diagnosis and prognosis.

Comparative Analysis of the Comfort of Children and Adolescents in Digital and Conventional Full-Arch Impression Methods: A Crossover Randomized Trial.

The aim of this study was to evaluate the comfort of children and adolescents with conventional full-arch dental impression methods compared to two intraoral scanners (iTeroTM and PrimescanTM). METHODS: A monocentric, analytical, controlled crossover study was designed to compare conventional impression and digital impression with two intraoral scanners (iTeroTM and PrimescanTM) in children and teenagers. Patient comfort was evaluated using a 100 mm VAS scale adapted to Spanish and for children. A descriptive and analytical statistical method was conducted with a confidence level of 95% (p ≤ 0.05) and asymptotic or bilateral significance. RESULTS: A total of 51 subjects were enrolled in the study (mean age = 12.35 years). Although the group of 10-14-year-olds was the most numerous, gender was equally distributed among the age groups. None of the variables on the VAS scale showed differences between the gender categories (p > 0.05). There were differences (p < 0.05) with respect to the age categories, as the middle adolescent group showed the worst general perception and total comfort during the conventional impression. Statistically significant differences were found between all VAS scale items and the three impression methods (p < 0.05). CONCLUSIONS: The digital impression technique is superior in terms of total comfort to the conventional alginate impression in children and adolescents.

Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques.

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques. The characterization strategy and the analytical measurements described here will have an important role during formulation development and in determining robust quality attributes ultimately supporting the quality assessment of these innovative RNA therapeutics.

Simultaneous evaluation of iris area and subfoveal choroidal thickness in Fuchs uveitis syndrome.

BACKGROUND/AIMS: To simultaneously evaluate iris area (IA) and subfoveal choroidal thickness (SFCT) in eyes with Fuchs Uveitis Syndrome (FUS). METHODS: We prospectively recruited a case series of patients with FUS at our institution, simultaneously measuring IA with anterior segment spectral domain optical coherence tomography (SD-OCT) and SFCT with enhanced depth imaging optical coherence tomography (EDI-OCT). Iris images were analyzed by ImageJ software. We tested the differences in intereye IA and SFCT with the healthy eye (HE) using the Wilcoxon test, and clinical interpretation was controlled by intraclass correlation coefficient (ICC) between two masked specialists. RESULTS: Sixteen patients with unilateral FUS were included. Six were female, and the age range was 37 to 67 (median age 48 years, IQR 41-60). ICC of 98.9%, with a lower confidence interval of 97%. Eyes with FUS had a significant thinning of the total iris median area (p < 0.002), restricted to the temporal and nasal areas compared to the HE (p < 0.01 and < 0.001, respectively). SFCT was also significantly thinner compared to the HE (p < 0.0001). A low correlation was found between iris and choroidal thinning in FUS eyes (rs = 0.21; p = 0.4). CONCLUSIONS: This study found reduced iris area and subfoveal choroidal thickness in eyes with FUS compared to the normal fellow eye.

The rational modulation of autophagy sensitizes colorectal cancer cells to 5-fluouracil and oxaliplatin.

Colorectal cancer (CRC) is the third most common and deadliest cancer globally. Regimens using 5-fluorouracil (5FU) and Oxaliplatin (OXA) are the first-line treatment for CRC, but tumor recurrence is frequent. It is plausible to hypothesize that differential cellular responses are triggered after treatments depending on the genetic background of CRC cells and that the rational modulation of cell tolerance mechanisms like autophagy may reduce the regrowth of CRC cells. This study proposes investigating the cellular mechanisms triggered by CRC cells exposed to 5FU and OXA using a preclinical experimental design mimicking one cycle of the clinical regimen (i.e., 48 h of treatment repeated every 2 weeks). To test this, we treated CRC human cell lines HCT116 and HT29 with the 5FU and OXA, combined or not, for 48 h, followed by analysis for two additional weeks. Compared to single-drug treatments, the co-treatment reduced tumor cell regrowth, clonogenicity and stemness, phenotypes associated with tumor aggressiveness and poor prognosis in clinics. This effect was exerted by the induction of apoptosis and senescence only in the co-treatment. However, a week after treatment, cells that tolerated the treatment had high levels of autophagy features and restored the proliferative phenotype, resembling tumor recurrence. The pharmacologic suppression of early autophagy during its peak of occurrence, but not concomitant with chemotherapeutics, strongly reduced cell regrowth. Overall, our experimental model provides new insights into the cellular mechanisms that underlie the response and tolerance of CRC cells to 5FU and OXA, suggesting optimized, time-specific autophagy inhibition as a new avenue for improving the efficacy of current treatments.

Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.

Few cancers can be targeted efficiently by engineered T cell strategies. Here, we show that γδ T cell antigen receptor (γδ TCR)-mediated cancer metabolome targeting can be combined with targeting of cancer-associated stress antigens (such as NKG2D ligands or CD277) through the addition of chimeric co-receptors. This strategy overcomes suboptimal γ9δ2 TCR engagement of αß T cells engineered to express a defined γδ TCR (TEGs) and improves serial killing, proliferation and persistence of TEGs. In vivo, the NKG2D-CD28WT chimera enabled control only of liquid tumors, whereas the NKG2D-4-1BBCD28TM chimera prolonged persistence of TEGs and improved control of liquid and solid tumors. The CD277-targeting chimera (103-4-1BB) was the most optimal co-stimulation format, eradicating both liquid and solid tumors. Single-cell transcriptomic analysis revealed that NKG2D-4-1BBCD28TM and 103-4-1BB chimeras reprogram TEGs through NF-κB. Owing to competition with naturally expressed NKG2D in CD8+ TEGs, the NKG2D-4-1BBCD28TM chimera mainly skewed CD4+ TEGs toward adhesion, proliferation, cytotoxicity and less exhausted signatures, whereas the 103-4-1BB chimera additionally shaped the CD8+ subset toward a proliferative state.

Efficient Identification of Patients With NTRK Fusions Using a Supervised Tumor-Agnostic Approach.

CONTEXT.­: The neurotrophic tropomyosin receptor kinase (NTRK) family gene rearrangements have been recently incorporated as predictive biomarkers in a "tumor-agnostic" manner. However, the identification of these patients is extremely challenging because the overall frequency of NTRK fusions is below 1%. Academic groups and professional organizations have released recommendations on the algorithms to detect NTRK fusions. The European Society for Medical Oncology proposal encourages the use of next-generation sequencing (NGS) if available, or alternatively immunohistochemistry (IHC) could be used for screening with NGS confirmation of all positive IHC results. Other academic groups have included histologic and genomic information in the testing algorithm. OBJECTIVE.­: To apply some of these triaging strategies for a more efficient identification of NTRK fusions within a single institution, so pathologists can gain practical insight on how to start looking for NTRK fusions. DESIGN.­: A multiparametric strategy combining histologic (secretory carcinomas of the breast and salivary gland; papillary thyroid carcinomas; infantile fibrosarcoma) and genomic (driver-negative non-small cell lung carcinomas, microsatellite instability-high colorectal adenocarcinomas, and wild-type gastrointestinal stromal tumors) triaging was put forward. RESULTS.­: Samples from 323 tumors were stained with the VENTANA pan-TRK EPR17341 Assay as a screening method. All positive IHC cases were simultaneously studied by 2 NGS tests, Oncomine Comprehensive Assay v3 and FoundationOne CDx. With this approach, the detection rate of NTRK fusions was 20 times higher (5.57%) by only screening 323 patients than the largest cohort in the literature (0.30%) comprising several hundred thousand patients. CONCLUSIONS.­: Based on our findings, we propose a multiparametric strategy (ie, "supervised tumor-agnostic approach") when pathologists start searching for NTRK fusions.

KRAS mutations in pancreatic cancer: could we talk about a risk factor for the development of thromboembolic phenomena?

The oncogenic KRAS mutation is associated with increased tissue factor expression and thus hypercoagulability. In this regard, numerous studies published in the last decade have shown that KRAS mutations are an important risk factor for the development of thromboembolic phenomena in neoplasms of the digestive tract, such as colorectal cancer. On the other hand, some recently published studies suggest that KRAS mutations are also associated with an increased risk of developing thromboembolic phenomena in pancreatic cancer. Based on these premises, we have conducted a single-centre retrospective study on a cohort of patients with pancreatic cancer. Our aim is to demonstrate whether there is an association between the presence of KRAS mutations in our cohort of pancreatic cancer patients and an increased risk of developing thromboembolic phenomena.

Subdermal Progestin Implant and an Oral Combined Hormonal Contraceptive in Youth with Type 1 Diabetes.

STUDY OBJECTIVE: To determine the metabolic effects of the subcutaneous etonogestrel implant compared with an oral contraceptive in adolescents and young adults (AYAs) with type 1 diabetes (T1D) on body weight, body composition, glucose, lipids, and C-reactive protein levels. METHODS: This was a non-randomized, interventional, prospective study. Thirty-nine AYAs with T1D participated; 20 used the implant (Implant-T1D), and 19 used an oral combined contraceptive (OC-T1D). Body composition, HbA1c, intermittent continuous glucose monitoring, lipids, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated. RESULTS: All participants were followed for at least 12 months, and 26 completed the 24-month follow-up. No women discontinued the intervention due to adverse effects. Body weight increased by 0.8 ± 3.5 and 1 ± 2.9 kg in the OC-T1D and the Implant-T1D group at 12 months and by 2.6 ± 3.9 and 3.3 ± 3.6 kg at 24 months, respectively. OC-T1D and Implant-T1D had similar HbA1c, mean interstitial glucose levels, and time in range throughout the study; no significant difference over time was observed. hsCRP levels increased in both groups and were associated with BMI and HbA1c (P < .001 for both variables). Women in the OC-T1D group had higher total cholesterol, HDL-C, and triglyceride levels compared with the Implant-T1D. CONCLUSION: Glucose levels were similar in youth using the subdermal progestin implant and an OC. However, both AYA groups showed increased BMI, fat mass, and subclinical inflammation. Changes in lipid levels were associated with the OC method. These data highlight the importance of weight gain prevention in young women with T1D using hormonal contraception.

Autophagy and nuclear morphometry are associated with histopathologic features in esophageal squamous cell carcinoma.

Less than 15% of patients with esophageal squamous cell carcinoma (ESCC) survive 5 years after diagnosis. A better understanding of the biology of these tumors and the development of clinical biomarkers is needed. Autophagy is a physiological mechanism involved in the turnover of cellular components that plays a key role in cancer. This study evaluated the differential levels of three key regulators of autophagy (SQSTM1, MAP1LC3B, and BECN1) in patients with ESCC, associating autophagy with histopathologic features, including the grade of differentiation, mitotic rate, inflammation score, and the intensity of tumor-infiltrating lymphocytes. Nuclear morphometry of the tumor parenchyma was also assessed, associating it with autophagy and histopathology. All three markers significantly increased in patients with ESCC compared to the control group. Based on the mean expression of each protein in the control group, 57% of patients with ESCC had high levels of all three markers compared to control patients (14%). The most frequent profiles found in ESCC were BECNhigh/MAP1LC3high and BECNhigh/SQSTM1high. According to the TCGA database, we found that the main autophagy genes were upregulated in ESCC. Moreover, high levels of autophagy markers were associated with a poor prognosis. Considering nuclear morphometry, ESCC samples showed a significant reduction in nuclear area, which was strongly negatively correlated with autophagy. Finally, the percentage of normal nuclei was associated with tumor differentiation, while poorly differentiated tumors showed lower SQSTM1 levels. ESCC progression may involve increased autophagy and changes in nuclear structure, associated with clinically relevant histopathological features. KEY MESSAGES: Autophagy markers are co-increased in primary ESCC. Autophagy negatively correlates with nuclear morphometry in ESCC parenchyma. Autophagy and nuclear morphometry are associated with histopathological features. Autophagy is increased in ESCC-TCGA database and associated with poor prognosis.

Dobutamine use in horses during romifidine and isoflurane anaesthesia.

This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and romifidine during elective surgery. Time from induction of anaesthesia to administration of dobutamine was registered, as well as the time and dose needed to restore mean arterial pressure (MAP) ≥ 70 mmHg. Additionally, the influence of patient and anaesthesia related parameters on the need for dobutamine supplementation was evaluated. In total, 118 horses were included in this retrospective study. Dobutamine was administered to effect when MAP<70 mmHg. Data registered: patient weight, acepromazine premedication, body position, administration of intraoperative ketamine bolus, locoregional anaesthesia, mechanical ventilation, duration of anaesthesia, dose and duration of dobutamine administration, heart rate, MAP before dobutamine administration, MAP and time required to increase MAP≥70 mmHg. Dobutamine infusion was needed in 54.2% of the horses 30 ± 17 min after isoflurane-romifidine anaesthesia started. Dobutamine 0.55 ± 0.18 µg kg-1 min-1 achieved a MAP≥70 mmHg in 12 ± 8 min. Duration of dobutamine infusion was 56 ± 37 min. An univariable logistic regression showed a significant association between dobutamine and acepromazine administration (p = 0.01; OR = 3.43), anaesthesia time (p = 0.02; OR = 2.41) and dorsal recumbency (p < 0.001; OR = 8.40). In a multivariable logistic regression, only dorsal recumbency significantly increased the need for dobutamine supplementation (p < 0.001; OR = 7.70). There was no significant association between patient weight (p = 0.11; OR = 1), locoregional anaesthesia (p = 0.07; OR = 0.47), administration of a ketamine bolus (p = 0.95; OR = 0.98) or volume controlled ventilation (p = 0.94; OR = 1.04) and dobutamine administration. Low doses of dobutamine were suitable to restore MAP above 70 mmHg within a limited time period. Only dorsal recumbency increased the need of dobutamine administration.

The potential role of apigenin in the enhancement of the antioxidant adaptation to exercise by bioactive dietary compounds

Oxidative stress (OS) occurs when the antioxidant defense system is overwhelmed by the predominance of reactive oxygen species (ROS) and pro-oxidant factors. Several diseases such as hypertension, insulin resistance, type 2 diabetes mellitus and neurodegenerative diseases are characterized by chronic OS. Physical exercise constitutes an affordable tool to prevent or ameliorate these conditions. However, during physical activity, acute ROS are produced inducing an activation in peroxisome proliferator activated receptor-Gamma Coactivator-1alpha (PGC-1α), and nuclear factor erythroid-2 related factor 2 (Nrf2), PGC-1α/Nrf2 pathway. This signaling pathway facilitates interaction with antioxidant response elements (ARE), thereby initiating an upregulation in the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and mitochondrial biogenesis. In both cases, whether involving healthy animals or individuals engaged in physical exercise, supplementation with antioxidant scavengers leads to a reduction in the expression and activity of PGC-1α, SOD, CAT, and GPX across various tissues, which is not observed with indirect antioxidants. The preventive role of physical exercise against chronic OS is avoided when executed in conjunction with supplementation of scavenger antioxidants. However, similar to exercise, the indirect antioxidant apigenin can activate the PGC1-α/Nrf2 signaling pathway. Here, we summarize evidence supporting apigenin as a non-nutritional supplement that could enhance the adaptive effects of exercise, improving the endogenous antioxidant defense. Therefore, apigenin could be an interesting supplement to enhance the endogenous antioxidant adaptation induced by exercise in healthy subjects, but also to improve the effectiveness of exercise to prevent oxidative stress-associated diseases.

El estrés oxidativo (OS) ocurre cuando el sistema de defensa antioxidante es sobrepasado por el predominio de especies reactivas de oxígeno (ROS) y factores prooxidantes. Varias enfermedades como la hipertensión, la resistencia a la insulina, la diabetes mellitus tipo 2 y enfermedades neurodegenerativas se caracterizan por un OS crónico. El ejercicio físico constituye una herramienta asequible para prevenir o mejorar estas enfermedades. Sin embargo, durante la actividad física, se producen ROS agudas que inducen una activación en la vía PGC-1α/Nrf2. Esta vía de señalización facilita la interacción con los elementos de respuesta antioxidante (ARE), iniciando así una regulación que permite la expresión de enzimas antioxidantes, incluidas SOD, CAT, GPX y biogénesis mitocondrial. En ambos casos, ya sea que se trate de animales sanos o de individuos que practican ejercicio físico, la suplementación con antioxidantes "scavengers" conduce a una reducción en la expresión y actividad de PGC-1α, SOD, CAT y GPX en varios tejidos, lo que no se observa con antioxidantes "indirectos". El papel preventivo del ejercicio físico contra el OS crónico se atenúa cuando se realiza en conjunto con la suplementación de antioxidantes "scavengers". Sin embargo, de manera similar al ejercicio, la apigenina es un antioxidante "indirecto" que puede activar la vía de señalización PGC1-α/Nrf2. Aquí, resumimos la evidencia que respalda a apigenina como un suplemento no-nutricional que podría mejorar los efectos adaptativos del ejercicio, mejorando la defensa antioxidante endógena de sujetos sanos que no tienen suficiente tiempo para hacer ejercicio.

Antibiotic Utilization in Hospitalized Children with Bronchiolitis: A Prospective Study Investigating Clinical and Epidemiological Characteristics at a Secondary Hospital in Madrid (2004-2022).

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

Mpox: Clinical Outcomes and Impact of Vaccination in People with and without HIV: A Population-Wide Study.

We investigated differences in mpox clinical outcomes in people with HIV (PWH) and without HIV (PWoH) and the impact of vaccination in Catalonia, Spain. We used surveillance data and the PISCIS HIV cohort. We included all confirmed mpox cases (May-December 2022). Of 2122 mpox cases, the majority had mild disease, 56% were Spanish, and 24% were from Latin America. A total of 40% were PWH, with a median CD4+T-cell of 715 cells/µL; 83% had HIV-RNA < 50 copies/mL; and 1.8% CD4+T-cell < 200 cells/µL. PWH had no increased risk for complications, except those with CD4+T-cell < 200 cells/µL. PWH with CD4+T-cell < 200 cells/µL were more likely to be from Latin America, had more generalized exanthema, and required hospitalization more frequently (p = 0.001). Diagnosis of other sexually transmitted infections (STIs) was common, both at mpox diagnosis (17%) and two years before (43%). Dose-sparing smallpox intradermal vaccination was accompanied by a sharp decrease in mpox incidence in both populations (p < 0.0001). In conclusion, unless immunosuppressed, PWH were not at increased risk of severe disease or hospitalization. Mpox is a marker of high-risk sexual behavior and was associated with high HIV and STI rates, supporting the need for screening in all mpox cases. Ethnicity disparities demonstrate the need for interventions to ensure equitable healthcare access. Dose-sparing smallpox vaccination retained effectiveness.

Impact of time of culture specimen collection on the recovery of Neisseria gonorrhoeae after a positive nucleic acid amplification test.

OBJECTIVES: Culture of Neisseria gonorrhoeae remains essential for antimicrobial resistance (AMR) surveillance. We evaluated the effect of time of specimen collection on culture yield following a positive nucleic acid amplification test (NAAT). METHODS: We retrospectively assessed N. gonorrhoeae culture yield among asymptomatic individuals (largely men who have sex with men) who attended for sexual health screening and had a positive NAAT. Participants underwent either same-day testing and notification (Drassanes Exprés) or standard screening with deferred testing. RESULTS: Among 10 423 screened individuals, 809 (7.7%) tested positive for N. gonorrhoeae. A total of 995 different anatomical sites of infection culture was performed in 583 of 995 (58.6%) of anatomical sites (Drassanes Exprés 278 of 347, 80.1%; standard screening 305 of 648, 47.1%; p<0.001). Recovery was highest when culture specimens were collected within 3-7 days of screening with only a slight drop in recovery when the interval extended to 7 days . Recovery from pharynx was 38 of 149 (25.5%) within 3 days, 19 of 81 (23.4%) after 4-7 days (p=0.7245), 11 of 102 (10.7%) after 8-14 days (p<0.0036) and 1 of 22 (4.5%) with longer delays (p=0.00287). Recovery from rectum was 49 of 75 (65.3%) within 3 days, 28 of 45 (62.2%) after 4-7 days (p=0.7318), 41 of 69 (59.4%) after 8-14 days (p=0.4651) and 6 of 18 (33.3%) with longer delays (p=0.0131). Median culture specimen collection time was 1 day within Drassanes Exprés vs 8 days within standard screening. Consequently, the overall culture yield was slightly higher within Drassanes Exprés (102/278, 36.6% vs 99/305, 32.5%; p=0.2934). CONCLUSION: Reducing the interval between screening and collection of culture specimens increased N. gonorrhoeae recovery in extragenital samples. Implementing a same-day testing and notification programme increased collection of culture samples and culture yield in our setting, which may help AMR surveillance.

Pharmacokinetics and Anti-Tumor Efficacy of PEGylated Liposomes Co-Loaded with Cisplatin and Mifepristone.

Although cisplatin is an effective chemotherapy drug used against many types of cancer, it has poor bioavailability, produces severe adverse effects, and frequently leads to tumor resistance. Consequently, more effective formulations are needed. The co-administration of cisplatin with mifepristone, which counters an efflux pump drug-resistance mechanism in tumor cells, has shown important synergism, but without resolving the problem of poor bioavailability. Specificity to tumor tissue and bioavailability have been improved by co-encapsulating cisplatin and mifepristone in a liposomal formulation (L-Cis/MF), which needs further research to complete pre-clinical requirements. The aim of this current contribution was to conduct a pharmacokinetic study of cisplatin and mifepristone in male Wistar rats after administration of L-Cis/MF and the conventional (unencapsulated) formulation. Additionally, the capacity of L-Cis/MF to reduce tumor growth in male nude mice was evaluated following the implantation of xenografts of non-small-cell lung cancer. The better pharmacokinetics (higher plasma concentration) of cisplatin and mifepristone when injected in the liposomal versus the conventional formulation correlated with greater efficacy in controlling tumor growth. Future research on L-Cis/MF will characterize its molecular mechanisms and apply it to other types of cancer affected by the synergism of cisplatin and mifepristone.

Near-Infrared Fluorescence Imaging in Preclinical Models of Glioblastoma.

Cancer is a public health problem requiring ongoing research to improve current treatments and discover novel therapies. More accurate imaging would facilitate such research. Near-infrared fluorescence has been developed as a non-invasive imaging technique capable of visualizing and measuring biological processes at the molecular level in living subjects. In this work, we evaluate the tumor activity in two preclinical glioblastoma models by using fluorochrome (IRDye 800CW) coupled to different molecules: tripeptide Arg-Gly-Asp (RGD), 2-amino-2-deoxy-D-glucose (2-DG), and polyethylene glycol (PEG). These molecules interact with pathological conditions of tumors, including their overexpression of αvß3 integrins (RGD), elevated glucose uptake (2-DG), and enhanced permeability and retention effect (PEG). IRDye 800CW RGD gave the best in vivo fluorescence signal from the tumor area, which contrasted well with the low fluorescence intensity of healthy tissue. In the ex vivo imaging (dissected tumor), the accumulation of IRDye 800CW RGD could be appreciated at the tumor site. Glioblastoma tumors were presently detected with specificity and sensitivity by utilizing IRDye 800CW RGD, a near-infrared fluorophore combined with a marker of αvß3 integrin expression. Further research is needed on its capacity to monitor tumor growth in glioblastoma after chemotherapy.