Postintensive care syndrome in patients and family members. Analysis of COVID-19 and non-COVID-19 cohorts, with face-to-face follow-up at three months and one year.

OBJECTIVE: Compare prevalence and profile of post-intensive care patient (P-PICS) and family/caregiver (F-PICS) syndrome in two cohorts (COVID and non-COVID) and analyse risk factors for P-PICS. DESIGN: Prospective, observational cohort (March 2018-2023), follow-up at three months and one year. SETTING: 14-bed polyvalent Intensive Care Unit (ICU), Level II Hospital. PATIENTS OR PARTICIPANTS: 265 patients and 209 relatives. Inclusion criteria patients: age > 18 years, mechanical ventilation > 48 h, ICU stay > 5 days, delirium, septic shock, acute respiratory distress syndrome, cardiac arrest. Inclusion criteria family: those who attended. INTERVENTIONS: Follow-up 3 months and 1 year after hospital discharge. MAIN VARIABLES OF INTEREST: Patients: sociodemographic, clinical, evolutive, physical, psychological and cognitive alterations, dependency degree and quality of life. Main caregivers: mental state and physical overload. RESULTS: 64.9% PICS-P, no differences between groups. COVID patients more physical alterations than non-COVID (P = .028). These more functional deterioration (P = .005), poorer quality of life (P = .003), higher nutritional alterations (P = .004) and cognitive deterioration (P < .001). 19.1% PICS-F, more frequent in relatives of non-COVID patients (17.6% vs. 5.5%; P = .013). Independent predictors of PICS-P: first years of the study (OR: 0.484), higher comorbidity (OR: 1.158), delirium (OR: 2.935), several reasons for being included (OR: 3.171) and midazolam (OR: 4.265). CONCLUSIONS: Prevalence PICS-P and PICS-F between both cohorts was similar. Main factors associated with the development of SPCI-P were: higher comorbidity, delirium, midazolan, inclusion for more than one reason and during the first years.

Age and Sex Differences in the Contribution of Mean Arterial Pressure to Pulse Pressure Before Middle Age.

INTRODUCTION: A lower ability to buffer pulse pressure (PP) in the face of increasing mean arterial pressure (MAP) may underlie the disproportionate increase in systolic blood pressure (SBP) in women from young adulthood through middle-aged relative to men. AIM: To evaluate the contribution of MAP to the change in PP and pressure wave contour in men and women from young adulthood to middle age. METHODS: Central pressure waveform was obtained from radial artery applanation tonometry in 312 hypertensive patients between 16 to 49 years (134 women, mean age 35 ± 9 years), 185 of whom were on antihypertensive treatment. RESULTS: Higher MAP levels (≥ 100 mmHg) were significantly associated with higher brachial and central SBP (P < 0.001), PP (P < 0.001), incident wave (P = 0.005), AP (P < 0.001), and PWV (P < 0.001) compared to lower MAP levels. The relationship between MAP and brachial PP (P < 0.001), central PP (P < 0.001), incident wave (P < 0.001), and AP (P < 0.01), but not PWV, strengthens with age. The age-related increase in the contribution of MAP to brachial PP (P < 0.001), central PP (P < 0.001), and incident wave (P < 0.001) was more prominent in women than in men beginning in the fourth decade. In multiple regression analyses, MAP remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of age, heart rate, and antihypertensive treatment. In turn, age remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of MAP, heart rate, and antihypertensive treatment. CONCLUSIONS: Women of reproductive age showed a steeper increase in PP with increasing MAP, despite comparable increases in arterial stiffness in both sexes. The difference was driven by a greater contribution of MAP to the forward component of the pressure wave in women.

Wastewater monitoring of SARS-CoV-2 gene for COVID-19 epidemiological surveillance in Tucumán, Argentina.

Wastewater-based epidemiology provides temporal and spatial information about the health status of a population. The objective of this study was to analyze and report the epidemiological dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the province of Tucumán, Argentina during the second and third waves of coronavirus disease 2019 (COVID-19) between April 2021 and March 2022. The study aimed to quantify SARS-CoV-2 RNA in wastewater, correlating it with clinically reported COVID-19 cases. Wastewater samples (n = 72) were collected from 16 sampling points located in three cities of Tucumán (San Miguel de Tucumán, Yerba Buena y Banda del Río Salí). Detection of viral nucleocapsid markers (N1 gene) was carried out using one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Viral loads were determined for each positive sample using a standard curve. A positive correlation (p < 0.05) was observed between viral load (copies/mL) and the clinically confirmed COVID-19 cases reported at specific sampling points in San Miguel de Tucumán (SP4, SP7, and SP8) in both months, May and June. Indeed, the high viral load concurred with the peaks of COVID-19 cases. This method allowed us to follow the behavior of SARS-CoV-2 infection during epidemic outbreaks. Thus, wastewater monitoring is a valuable epidemiological indicator that enables the anticipation of increases in COVID-19 cases and tracking the progress of the pandemic. SARS-CoV-2 genome-based surveillance should be implemented as a routine practice to prepare for any future surge in infections.

Violence Exposure and Disability in Colombian Female Survivors of Intimate Partner Violence: the Mediating Role of Depressive Symptoms.

BACKGROUND: Violence is an important public health problem and one of the main causes of deaths worldwide. The mental health consequences of surviving intimate partner violence (IPV) include depression, anxiety and post-traumatic stress disorder. Previous studies have identified that there is a relationship between depression and level of disability in female survivors of IPV. Estimating the direct, indirect or total effect of an exposure on an outcome makes it possible to identify mediating effects between a group of variables. Detecting mediation effects is useful for identifying casual pathways that generate a final outcome and provides a rationale for designing interventions to target the mediator, which in turn positively affects the outcome. The objective was to identify the mediating role of depressive symptoms on the relationship between IPV and disability. METHODS: This was a cross-sectional study of 94 women over the age of 18 who were survivors of IPV by men. They were recruited from two public hospitals in Cali and Tuluá in southwest Colombia. An analysis of casual relationships was performed using structural equation modelling that was made up of: four exogenous observed variables (age, current relationship status [in a relationship or single], level of schooling, and history of an impairment), intermediate endogenous variables (violence and depressive symptoms), and the main endogenous variable (disability). The analyses were carried out in Stata14.2. RESULTS: The direct effect of IPV severity on the level of disability was not statistically significant (ß=0.09; P=0.63). However, the indirect effect of IPV severity on disability mediated by depressive symptoms was (ß=0.39; P<0.01). The total effect of IPV severity on the level of disability was even greater (ß=0.48; P=0.01). CONCLUSIONS: This study found a complete mediating role of depressive symptoms on the relationship between the severity of IPV and the level of disability for the female participants in this study. The results of this research contribute to defining strategies to prevent and address intimate partner violence, depressive symptoms and disability in this population.

Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

Introduction and objectives Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. Methods The REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF > 10% (provided the LVEF is < 50%); b) a reduction in LVEF > 10% accompanied by an increase > 15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. Conclusions The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

Glutamine promotes human CD8+ T cells and counteracts imiquimod-induced T cell hyporesponsiveness.

T cells protect tissues from cancer. Although investigations in mice showed that amino acids (AA) critically regulate T cell immunity, this remains poorly understood in humans. Here, we describe the AA composition of interstitial fluids in keratinocyte-derived skin cancers (KDSCs) and study the effect of AA on T cells using models of primary human cells and tissues. Gln contributed to ∼15% of interstitial AAs and promoted interferon gamma (IFN-γ), but not granzyme B (GzB) expression, in CD8+ T cells. Furthermore, the Toll-like receptor 7 agonist imiquimod (IMQ), a common treatment for KDSCs, down-regulated the metabolic gatekeepers c-MYC and mTORC1, as well as the AA transporter ASCT2 and intracellular Gln, Asn, Ala, and Asp in T cells. Reduced proliferation and IFN-γ expression, yet increased GzB, paralleled IMQ effects on AA. Finally, Gln was sufficient to promote IFN-γ-production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.

Red Blood Cell Polyunsaturated Fatty Acids and Mortality Following Breast Cancer.

BACKGROUND: Intake of polyunsaturated fatty acids (PUFAs) may impact mortality following breast cancer (BC); however, epidemiological studies have relied on self-reported assessment of PUFA intake. Herein, we examined the associations between red blood cell (RBC) PUFAs and mortality. METHODS: This nested case-control study included 1,104 women from, the Women's Healthy Eating and Living Study, a multi-site randomized controlled trial. Cases (n=290) were women who died from 1995-2006. Matched controls (n=814) were women who were alive at the end of follow-up. PUFAs were measured in baseline RBC samples and included four ω-3 and seven ω-6 PUFAs. We examined each PUFA individually and Principal Components Factor Analysis (PCFA)-derived scores in association with all-cause mortality (ACM) and BC-specific mortality (BCM) using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully-adjusted models, ACM ORs were elevated among women with PUFAs >median (versus ≤median) for α-linolenic acid (ALA, OR=1.63, 95%CI=1.18-2.24) and for linolenic acid (LA, OR=1.56, 95%CI=1.16-2.09), and BCM ORs were elevated for ALA (OR=1.83, 95%CI=1.27-2.63), LA (OR=1.70, 95%CI=1.23-2.37), and γ-linolenic acid (GLA, OR=1.50; 95%CI=1.04-2.16). PCFA-Factor 1 [arachidonic acid/adrenic acid/docosapentaenoic acid] scores >median (versus ≤median) were associated with lower odds of ACM (OR=0.71; 95%CI=0.52-0.97) and BCM (OR=0.69; 95%CI=0.49-0.97), and PCFA-Factor 4 [ALA/GLA] scores >median (versus ≤median) were associated with increased odds of BCM (OR=1.47; 95%CI=1.04-2.09). CONCLUSIONS: RBC ALA, LA, and GLA may be prognostic indicators among BC survivors. IMPACT: These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors.

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.

BACKGROUND: The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo. OBJECTIVES: A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143). METHODS: Eighty participants were randomized. In single ascending dose (SAD), a total of six dose levels of alpibectir (0.5 to 40 mg) were tested under fasted and fed (10 mg) conditions as single daily doses in sequential cohorts. In multiple ascending dose (MAD), repeat doses (5 to 30 mg) were administered once daily for 7 days in three sequential cohorts. RESULTS: No serious adverse event was reported. Thirteen participants across groups experienced a total of 13 mild or moderate treatment-emergent adverse events. Alpibectir showed rapid absorption after single dose (mean Tmax range of 0.88 to 1.53 h). Food affected the PK of alpibectir, characterized by a slower absorption (mean Tmax 3.87 h), a lower Cmax (-17.7%) and increased AUC0-t (+19.6%) compared with the fasted condition. Following repeat dosing, dose proportionality was shown for both Cmax and AUC0-tau. Accumulation of alpibectir was observed across all doses, with a more profound effect on AUC during a dosing interval (AUC0-tau) compared with Cmax (1.8- and 1.3-fold on average), respectively. Steady state was considered to have been achieved by Day 7 of dosing. CONCLUSIONS: Alpibectir was generally well tolerated, and no clinically relevant safety findings were identified in the participants treated during SAD or MAD. The PK is dose-proportional and affected by food.

Validation of the Health Index in the Postoperative Period: Use of the Nursing Outcome Classification to Determine the Health Level.

BACKGROUND: The postoperative period is the recovery time after surgery and is defined as an individual process whose purpose is to return the person to the state of normality and integrity that they had prior to surgery. AIM: Demonstrate the modification of the level of health of people in the early postoperative period through the development and validation of the Health Index Instrument, which is built from the Nursing Outcomes Classification (NOC) standardized language. DESIGN: The design used a mixed method, which involved a first phase of instrument development and a second phase of instrument validation. METHODS: The methods was based on focus group techniques with text analysis techniques, internal validation with a group of care language experts, external validation with a group of clinical nursing experts and a clinical validation with quantitative and qualitative analysis. A panel of experts in Language of Care evaluated the (NOC) labels and their correlation with the 11 Health Variables to construct the instrument. The instrument developed was subjected to external validation with a panel of clinical nurse experts in post-anesthesia care. The clinical validation included a cross-sectional descriptive study in a postoperative unit. The final sample of the cross-sectional descriptive study was 139 cases. RESULTS: Of the 89 NOCs proposed in the preliminary construction phase of the instrument, 36 passed through the first round. Of those 36 NOCs, 25 passed through to the second round with a review performance and 11 directly as approved. The total number of approved NOCs were 4. The results of the research show that there are changes in the global score of the health level and in each health variable. It is observed that there was a significant increase in the scores of the health variables at admission and discharge (p < 0.001). CONCLUSIONS: The results of the data analysis show that six groups present a similar pattern of evolution of the health variables. A correlation was found between the time of stay in the unit with the scores obtained in the health variables, the physical functioning, comfort status and the presence of symptoms being particularly significant.

Comprehensive Analysis of Xiaomi Mi 8 GNSS Antenna Performance.

The interest in precise point positioning techniques using smartphones increased with the launch of the world's first dual-frequency L1/L5 GNSS smartphone, Xiaomi Mi 8. The smartphone GNSS antenna is low-cost, sensitive to multipath, and limited by physical space and design. The main purpose of this work is to determine the mechanical location and antenna performance in terms of radiation pattern in an anechoic chamber using a Vector Network Analyzer (VNA) and robotic positioning platform by varying the elevation and azimuth angles between the transmitter and smartphone GNSS antennas; the power received and satellite visibility are developed in an outdoor scenario. The results show a Planar Inverted-F Antenna with an omnidirectional radiation pattern without gain. The L1/E1/B1 and L5/E5a/B2a GNSS antennas are physically located at the top face of the screen, with dimensions of 48 × 17 mm and 60 × 13 mm, respectively. With the screen with line-of-sight toward the sky, L5 satellites have a better signal-noise ratio (SNR), unlike the back side, which loses 99% of the data in the PPP solution. Under multipath scenarios, the L1 GNSS smartphone antenna works with 25% less power than the GPS user segment recommendation, showing high sensitivity to track weak signals.

Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis / Valor pronóstico de los autoanticuerpos anti-IFI16 en la hipertensión arterial pulmonar y en la mortalidad en los pacientes con esclerodermia sistémica

Objectives: To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). Methods: Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. Results: Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). Conclusion: Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome. (AU)

Objetivos: Determinar el valor diagnóstico de los autoanticuerpos anti-interferon gamma inducible protein 16 (IFI16) en los pacientes con esclerodermia sistémica (SSc) negativos para todos los autoanticuerpos específicos de SSc (pacientes SSc seronegativos) y evaluar el significado clínico de estos autoanticuerpos, aislados o en combinación con autoanticuerpos anticentrómero (ACA). Métodos: Se incluyeron 58 pacientes SSc seronegativos y 66 pacientes ACA positivos. Todos los pacientes se testaron para los autoanticuerpos anti-IFI16 mediante un ELISA directo «in-house». Las asociaciones entre parámetros clínicos y los autoanticuerpos anti-IFI16 fueron analizadas. Resultados: En total, el 17,2% de los pacientes SSc seronegativos y el 39,4% de los pacientes ACA positivos fueron positivos para anti-IFI16. Los autoanticuerpos anti-IFI16 se detectaron solamente en los pacientes con la forma limitada cutánea de SSc (lcSSc). Se encontró una asociación entre la positividad de anti-IFI16 y la hipertensión arterial pulmonar (HAP) aislada (odds ratio [OR]: 5,07; p=0,014), incluso cuando se ajustó el análisis a la presencia o ausencia de ACA (OR: 4,99; p=0,019). Los pacientes anti-IFI16 positivos mostraron una peor supervivencia general que los pacientes negativos (p=0,032). Las ratios de supervivencia acumulada a 10, 20 y 30 años fueron respectivamente del 96,9, 92,5 y 68,7% para los pacientes anti-IFI16 positivos frente al 98,8, 97,0 y 90,3% para los anti-IFI16 negativos. Los pacientes anti-IFI16 positivos también tenían una supervivencia general menor que los pacientes anti-IFI16 negativos tras ajustar para la presencia o ausencia de ACA mediante análisis multivariado de Cox (hazard ratio [HR]: 3,21; p=0,043)... (AU)

Regeneración / revitalización pulpar en dientes permanentes inmaduros / Pulp regeneration / revitalization in immature permanent teeth

Introducción: El tratamiento pulpar de dientes inmaduros es un procedimiento desafi ante. Los dientes inmaduros tienen unos conductos anchos, paredes dentinarias delgadas y ápices abiertos, además de ser más propensos a la fractura y con mal pronóstico a largo plazo. La revascularización de un diente inmaduro intenta preservar los dientes el mayor tiempo posible, pero hay fracasos porque es difícil lograr una desinfección óptima del sistema de conductos radiculares. Métodos: Se realizó una búsqueda bibliográfi ca consultando las bases de datos electrónicas PubMed y Web of cience de los últimos 10 años, utilizando palabras clave y criterios de elegibilidad. Resultados: El proceso de búsqueda arrojó 635 artículos totales. Tras aplicar fi ltros, eliminar duplicados y seleccionar artículos por título y resumen, solo 27 fueron para el estudio. Conclusiones: La revitalización pulpar tiene altas tasas de supervivencia en el tratamiento de dientes permanentes inmaduros necróticos. Son necesarios ensayos clínicos aleatorios para comparar el efecto de la fi brina rica en plaquetas, el plasma rico en plaquetas y el sangrado inducido sobre la revitalización de un diente con pulpa necrótica. Uno de los principales problemas de la revitalización pulpar es la decoloración coronal. La triple pasta antibiótica es un agente antimicrobiano muy efi caz, pero las altas concentraciones podrían tener un efecto perjudicial sobre la supervivencia de las células madre. (AU)

Introduction: Treatment of affected immature teeth is a challenging procedure. Immature teeth have wide canals, thin dentin walls and open apices, in addition to being more prone to fracture and with a poor long-term prognosis. Revascularization of an immature tooth attempts to preserve the teeth as long as possible, but there are failures because it is diffi cult to achieve optimal disinfection of the root canal system. Methods: An exhaustive search was carried out by consulting the electronic databases PubMed and Web of Science of the last 10 years, using keywords and eligibility criteria. Results: The search process yielded 635 total articles. After applying fi lters, eliminating duplicates and selecting articles by title and abstract, only 27 were for the present study. Conclusions: Pulp revitalization has high survival rates in the treatment of necrotic immature permanent teeth. Randomized clinical trials are needed to compare the effect of platelet-richfi brin, platelet-rich plasma, and induced bleeding on the revitalization of a tooth with necrotic pulp. One of the main problems of pulp revitalization is coronal discoloration. Triple antibiotic paste is a very effective antimicrobial agent, but high concentrations could have a detrimental effect on stem cell survival. (AU)

Comparison of ddRADseq and EUChip60K SNP genotyping systems for population genetics and genomic selection in Eucalyptus dunnii (Maiden).

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

MicroRNA Expression Profiles in Human Samples and Cell Lines Revealed Nine miRNAs Associated with Cisplatin Resistance in High-Grade Serous Ovarian Cancer.

Metastasis and drug resistance are major contributors to cancer-related fatalities worldwide. In ovarian cancer (OC), a staggering 70% develop resistance to the front-line therapy, cisplatin. Despite proposed mechanisms, the molecular events driving cisplatin resistance remain unclear. Dysregulated microRNAs (miRNAs) play a role in OC initiation, progression, and chemoresistance, yet few studies have compared miRNA expression in OC samples and cell lines. This study aimed to identify key miRNAs involved in the cisplatin resistance of high-grade-serous-ovarian-cancer (HGSOC), the most common gynecological malignancy. MiRNA expression profiles were conducted on RNA isolated from formalin-fixed-paraffin-embedded human ovarian tumor samples and HGSOC cell lines. Nine miRNAs were identified in both sample types. Targeting these with oligonucleotide miRNA inhibitors (OMIs) reduced proliferation by more than 50% for miR-203a, miR-96-5p, miR-10a-5p, miR-141-3p, miR-200c-3p, miR-182-5p, miR-183-5p, and miR-1206. OMIs significantly reduced migration for miR-183-5p, miR-203a, miR-296-5p, and miR-1206. Molecular pathway analysis revealed that the nine miRNAs regulate pathways associated with proliferation, invasion, and chemoresistance through PTEN, ZEB1, FOXO1, and SNAI2. High expression of miR-1206, miR-10a-5p, miR-141-3p, and miR-96-5p correlated with poor prognosis in OC patients according to the KM plotter database. These nine miRNAs could be used as targets for therapy and as markers of cisplatin response.

Effectiveness of gamification in nursing degree education.

Background: Previous research in nursing has found favorable results from the use of teaching methodologies alternative to lectures. One of the complementary methodologies used for university teaching is gamification, or the inclusion of game elements, creating a dynamic learning environment that allows the acquisition of knowledge and the development of other skills necessary for nursing students. The purpose of this study was to evaluate the effect of a gamification session on student satisfaction and knowledge scores in nursing students in simulated laboratory practice. Methods: A pre-post quasi-experimental study was conducted with 122 students from the nursing degree program who participated in the research. The evaluation consisted of four sessions of three hours each. In two sessions, participants were trained through a vertical methodology, by means of theoretical training provided by teaching staff, and two hours of clinical simulation, where the students were able to practice the techniques on professional simulators. At the other two sessions, participants received an explanation of the theoretical aspects of the session, one hour of clinical simulation, and one hour of gamification, in which they had to pass tests based on the performance of practical activities on the subject of the session. At the end of the gamification session, all the participants received a certificate as winners of the "nursing game". Results: There was an improvement in the satisfaction and the knowledge level in the gamification sessions. Both were statistically significant (P < 0.001). There was an improvement in the items related to the development of critical thinking and the mobilizing concepts from theory to practice in the gamification sessions. Conclusion: The intervention was effective in improving the satisfaction of the sessions received and in knowledge development.

Accidental catheter breakage during caudal epidural infiltration in an adult: An unusual complication.

Caudal epidural block is a simple and safe technique with a low complication rate commonly used for pediatric anesthesia and treatment of chronic lumbosacral pain. However, it is not exempt from some risks that, although infrequent, should be known. We describe the case of a 48-year-old female with chronic lumbosacral radicular pain who underwent caudal epidural infiltration. During the withdrawal of the catheter, accidental breakage and retention of a fragment at the level of the anterior epidural space of the sacrum occurred. We choose to have an expectant management with regular controls and a radiological lumbosacral computed tomography (CT) scan. Since the catheter was placed under sterile conditions, no prophylactic antibiotic treatment was considered. The patient showed no adverse events during the 6 months following catheter rupture. To our knowledge, there are no reports of epidural catheter breakage at the caudal level in adults. This is why there is no standardized protocol on how to proceed in these cases, and the handling of this situation must be individualized.

Cone-Beam Computed Tomography for the Evaluation of Dental Pulp Chamber Volume: Implications for Clinics and Teaching.

The dental pulp chamber volume is a fundamental measurement in the field of endodontics, but also in forensic sciences, teaching and training, or tissue engineering. This study evaluates the precision of cone-beam computed tomography (CBCT) in comparison with computed micro-tomography (micro-CT) in evaluating the pulp chamber volume of the upper central incisors ex vivo. The intra-operator and inter-operator errors were evaluated, and the results for the two techniques were compared with those of a T-test for paired samples. The intra-operator and inter-operator errors were >0.05, indicating adequate reproducibility in each operator and no significant differences between their measurements. On the other hand, no significant differences between the two measurement techniques were found. The present results demonstrate that CBCT is a precise, feasible, and reproducible technique for the evaluation of the dental pulp chamber volume ex vivo. The results provided with this method are useful for different medical domains but also for the teaching and training of undergraduate and postgraduate students. Furthermore, the findings of this study carry significant clinical implications, as the accurate assessment of the pulp chamber volume is critical in the diagnosis and treatment of various endodontic conditions. The ability of CBCT to provide reliable 3D dental anatomy measurements can enhance the planning of endodontic treatments by allowing for a better understanding of the internal tooth morphology. Additionally, the precision and reproducibility of CBCT in assessing the pulp chamber volume can contribute to improved clinical outcomes and reduced complications during endodontic procedures. These findings further support the increasingly vital role of CBCT in modern clinical practice and underscore its value as an indispensable tool in the field of dentistry.

Comparison of the Effect of Two Different Handling Conditions at Slaughter in Saliva Analytes in Pigs.

In this report, different handling conditions at slaughterhouse were studied to assess changes in salivary biomarkers. For this purpose, finishing pigs were divided into two groups, one in which handling was improved to minimize stress (Group A, n = 24, transported and stabled at the slaughterhouse at low density without mixing with unfamiliar animals throughout the whole process) and another one in which animals had a more stressful handling process (Group B, n = 24, transported and stabled at high density with unfamiliar animals). Saliva samples were taken the day before transport to the slaughterhouse at 8:00 a.m. (B0) and 12:00 a.m. (B4), and the day of slaughter just after unloading animals at the slaughterhouse at approximately 8:00 a.m. (S0) and after 4 h of lairage at approximately 12:00 a.m. (S4). Group B showed significantly higher cortisol, total esterase activity, oxytocin, adenosine deaminase and haptoglobin levels than the Group A at both S0 and S4 sampling times, and higher levels of calprotectin and creatine kinase at S4 sampling time. This report indicates that differences in the way in which the pigs are handled at the slaughterhouse can lead to changes in salivary biomarkers and opens the possibility of the use of biomarker at slaughter to monitor handling conditions.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.