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Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (gBRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3–70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants., This research was funded by Astra Zéneca Farmacéutica Spain SA (Grant Number GEICO60-0).

This work faces the use of graphene liquid-gate transistors as sensors. Before dealing with a functionalized surface and biological targets, achieving a reliable sensing platform within this novel material as an active channel, fabrication, lithography, and reliability have to be extensively evaluated. In this work, we have analyzed the inter-device variability and the reliability of the sensors together with the phenomena which can increase these issues under operative conditions. High quality material corroboration has been evaluated through structural characterization (optical, XPS and Raman). Then photolithography and processing for liquid-gate sensor have been performed. Finally, electrical evaluation of the devices has been carried out demonstrating reliability issues and considerable inter-device variability. We propose in this work the use of integrate-coupling effect (front and back-gate simultaneously) to alleviate the inter-device variability and reliability problems.

Purpose: In the phase III CheckMate 238 study, adjuvant nivolumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB–C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings. Patients and Methods: Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. Results: At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR = 0.72; 95% confidence interval, 0.60–0.86; 5-year rates of 50% vs. 39%). Five-year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value. Conclusions: Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome.

MicroRNA (miRNA) has emerged as a promising alternative therapeutic treatment for cancer, but its delivery has been hindered by low cellular uptake and degradation during circulation. In this review, we discuss the various methods of delivering miRNA, including viral and non-viral delivery systems such as liposomes and nanoparticles. We also examine the use of nanoparticles for miRNA-based diagnostics. We focus specifically on non-viral delivery systems utilizing coinage metals in the form of nanoparticles and the use of self-assembled monolayers (SAMs) as a method of surface modification. We review the use of SAMs for the conjugation and delivery of small noncoding ribonucleic acid (ncRNA), particularly SAMs derived from positively charged adsorbates to generate charged surfaces that can interact electrostatically with negatively charged miRNA. We also discuss the effects of the cellular uptake of gold and other plasmonic nanoparticles, as well as the challenges associated with the degradation of oligonucleotides. Our review highlights the potential of SAM-based systems as versatile and robust tools for delivering miRNA and other RNAs in vitro and in vivo and the need for further research to address the challenges associated with miRNA delivery and diagnostics.

RESUMO: O objetivo deste artigo é debater como os impasses da adolescência contemporânea em um contexto de domínio do discurso neoliberal nas escolas pode ter como consequência a manifestão de atos de violência. Apresentamos como a adolescência tornou-se um ideal cultural por encarnar o ideário neoliberal de liberdade e satisfação plena. Apontamos as dificuldades na travessia da adolescência em função das modificações corporais, resignificação das relações com os pais e da necessidade de reconstrução do laço social. Por fim, discutimos como a violência escolar pode irromper a partir do acirramento das relações entre professores e estudantes como efeito das investidas do neoliberalismo na educação básica.

Purpose: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. Methods: A total of 245 VMAT HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included CT images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared to manual flags by 3 HN radiation oncologists. Results: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%, D95%, and D99% across the targets were within -2.53%(SD=1.34%), -0.42%(SD=1.27%), and -0.12%(SD=1.97%), respectively, and the OAR mean and maximum doses were within -0.33Gy(SD=1.40Gy) and -0.96Gy(SD=2.08Gy). For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. Conclusion: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality., Comment: updated to reflect the published peer-reviewed article

Within traumatic brain injury (TBI) care, there is growing interest in pathophysiological markers as surrogates of disease severity, which may be used to improve and individualize care. Of these, assessment of cerebrovascular reactivity (CVR) has been extensively studied given that it is a consistent, independent factor associated with mortality and functional outcome. However, to date, the literature supports little-to-no impact of current guideline-supported therapeutic interventions on continuously measured CVR. Previous work in this area has suffered from a lack of validation studies, given the rarity of time-matched high-frequency cerebral physiology with serially recorded therapeutic interventions; thus, we undertook a validation study. Utilizing the Winnipeg Acute TBI database, we evaluated the association between daily treatment intensity levels, as measured through the therapeutic intensity level (TIL) scoring system, and continuous multi-modal-derived CVR measures. CVR measures included the intracranial pressure (ICP)-derived pressure reactivity index, pulse amplitude index, and RAC index (a correlation between the pulse amplitude of ICP and cerebral perfusion pressure), as well as the cerebral autoregulation measure of near-infrared spectroscopy-based cerebral oximetry index. These measures were also derived over a key threshold for each day and were compared to the daily total TIL measure. In summary, we could not observe any overall relationship between TIL and these CVR measures. This validates previous findings and represents only the second such analysis to date. This helps to confirm that CVR appears to remain independent of current therapeutic interventions and is a potential unique physiological target for critical care. Further work into the high-frequency relationship between critical care and CVR is required.

Background: Early surgical resection is an emerging concept for patients with ileocaecal Crohn's disease (CD). The aim of this study was to compare postoperative outcomes after ileocaecal resections between patients with luminal and complicated CD. Methods: A retrospective analysis of patients operated for ileocaecal CD during an 8-year period in ten tertiary referral academic centres from Latin America was performed. Patients were allocated into 2 groups: those operated for early (luminal) disease (Early Crohn's Disease -ECD-) and for complications of CD (Complicated Crohn's disease -CCD-). A comparative analysis was performed regarding short-term outcomes of surgery, considering overall postoperative complications as main outcome. Results: 337 patients were included in the analysis, 60 (17.80%) in the ECD group. Smoking and exposure to perioperative biologic drugs were more prevalent in CCD group. CCD patients had increased requirement of urgent surgery (26.71 vs. 15%, p = 0.056), longer operative time (164.25 vs. 90.53 min, p< 0.01), lower rates of primary anastomosis (90.23 vs. 100%, p = 0.012), increased rate of overall postoperative complications (33.21 vs. 16.67%, p = 0.013), more reoperations (13.36 vs. 3.33%, p = 0.026), and higher rates of major anastomotic fistulas and hospital stay. On multivariable analysis, smoking (p = 0.001,95%CI: 2.59–32.11), operative time (p = 0.022,95%CI:1–1.02), associated procedures (p = 0.036,95%CI:1.09–15.72) and intraoperative complications (p = 0.021,95%CI:1.45–92.31) were independently related to presenting postoperative complications. Conclusion: Early (luminal) ileocaecal resections were associated to lower rates of overall postoperative complications. Proper timing for surgery, avoiding delays in surgical indication can impact postoperative outcomes.

Natural preservatives have less of a negative effect on human health and other systems, making them the superior choice over conventional preservatives. The purpose of this study was to evaluate the impact of propolis, a natural preservative, affected the flavour and texture of an artisanal hamburger made with alpaca meat (Vicugna pacos). An experimental design with 5 treatments was established, a control treatment of alpaca hamburger with artificial preservative (T1) and four experimental treatments with the addition of propolis (0.25 ml, 0.50 ml, 0.75 ml and 1.0 ml in 100 g of meat mixture). The Kruskal-Wallis non-parametric variance test and the Mann-Whitney non-parametric test were utilised to examine the data collected from the randomised full blocks design of the experiment. Thirty semi-trained tasters evaluated propolis on its general look, smell, taste, colour, and texture, in addition to its antibacterial effects on Staphylococcus aureus. The results showed that the bacterial count of S. aureus was kept at 1.5x10 CFU/g, which is between the allowable ranges of 102 and 103, suggesting that propolis has the ability to inhibit this bacteria. The sensory tests showed that the addition of propolis does not produce negative effects on the general appearance, smell, taste and texture compared to the control treatment (p > 0.05), only the color was affected (p < 0.05) only in doses greater than 0.5 ml per 100 g of meat mixture. In conclusion, the applicability of propolis as a preservative in the alpaca meat hamburger is verified.

SYNOPSIS Using a sample of S&P 500 companies, this study constructs a measure of CEO narcissism and examines whether and how it impacts the accuracy and dispersion of analysts’ forecasts. Empirical evidence suggests that firms with narcissistic CEOs have higher accuracy and lower dispersion of such forecasts. In investigating the mechanism through which CEO narcissism impacts these properties, we find that firms with narcissistic CEOs are more likely to issue management earnings guidance, albeit less accurate, which results in significant differences in accuracy and dispersion of analysts’ forecasts. This study concludes that through more management voluntary disclosure, CEO narcissism has a positive impact on the accuracy and a negative impact on the dispersion of financial analysts’ forecasts. Although several studies have explored the effect of CEO narcissism on corporate financial reporting, this is the first study to expand such inquiry into the sector of financial analysts. JEL Classifications: G17; M12; M41.

Extreme El Niño events stand out not only because they have powerful impacts but also because they are significantly different from other El Niños. In Ecuador, such events are accountable for negatively impacting the economy, infrastructure, and population. Spatial–temporal dynamics of precipitation anomalies from various types of extreme El Niño events are analyzed and compared. Results show that for eastern Pacific (EP) and coastal Pacific (COA) El Niño types, most precipitation extremes occur in the first half of the second year of the event. Any significant difference between events becomes more evident at this stage. Spatially, for any event, 50 % of all extreme anomalies occurred at elevations

We study the nuclear isentropic equation of state for a stellar matter composed of nucleons, hyperons, and $\Delta$-resonances. We investigate different snapshots of the evolution of a neutron star, from its birth as a lepton-rich protoneutron star in the aftermath of a supernova explosion to a lepton-poor regime when the star starts cooling to a catalyzed configuration. We use a relativistic model within the mean-field approximation to describe the hot stellar matter and adopt density-dependent couplings adjusted by the DDME2 parameterization. We use baryon-meson couplings for the spin-$1/2$ baryonic octet and spin-$3/2$ decuplet determined in a unified manner relying on $\text{SU}(6)$ and $\text{SU}(3)$ symmetry arguments. We observe that $\Lambda$ is the dominant exotic particle in the star at different entropies for both neutrino-free and neutrino-trapped stellar matter. For a fixed entropy, the inclusion of new particles (hyperons and/or delta resonances) in the stellar matter decreases the temperature. Also, an increase in entropy per baryon ($1\;\text{to}\; 2$) with decreasing lepton number density ($0.4\;\text{to}\; 0.2$) leads to an increase in stellar radii and a decrease in its mass due to neutrino diffusion. In the neutrino transparent matter, the radii decrease from entropy per baryon $2$ to $T\,=\,0$ without a significant change in stellar mass., Comment: 9 pages, 10 figures

Many marine algae occupy habitats that are dark, deep, or encrusted on other organisms and hence are frequently overlooked by natural product chemists. However, exploration of less-studied organisms can lead to new opportunities for drug discovery. Genetic variation at the individual, species, genus, and population levels as well as environmental influences on gene expression enable expansion of the chemical repertoire associated with a taxonomic group, enabling natural product exploration using innovative analytical methods. A nontargeted LC-MS and ¹H NMR spectroscopy-based metabolomic study of 32 collections of representatives of the calcareous red algal genus Peyssonnelia from coral reef habitats in Fiji and the Solomon Islands revealed significant correlations between natural products’ chemistry, phylogeny, and biomedically relevant biological activity. Hierarchical cluster analysis (HCA) of LC-MS data in conjunction with NMR profiling and MS/MS-based molecular networking revealed the presence of at least four distinct algal chemotypes within the genus Peyssonnelia. Two Fijian collections were prioritized for further analysis, leading to the isolation of three novel sulfated triterpene glycosides with a rearranged isomalabaricane carbon skeleton, guided by the metabolomic data. The discovery of peyssobaricanosides A–C (15–17) from two Fijian Peyssonnelia collections, but not from closely related specimens collected in the Solomon Islands that were otherwise chemically and phylogenetically very similar, alludes to population-level variation in secondary metabolite production. Our study reinforces the significance of exploring unusual ecological niches and showcases marine red algae as a chemically rich treasure trove.

Academic buoyancy is a student’s ability to effectively deal with academic setbacks and challenges. This study aimed to determine whether academic buoyancy predicts academic performance among high school students. The objective of this study was to investigate the relationship between academic buoyancy and academic performance among high school students. Participants were 142 high school students who completed a questionnaire that included measures of academic buoyancy and grade point average (GPA). Data were analyzed using simple linear regression and frequency distribution. The results showed that academic buoyancy predicted academic performance among high school students. About 11.6% of the variation in academic performance was explained by academic buoyancy. The average GPA of the participants was 86.51, and the average academic buoyancy score was 4.69. The findings suggest that academic buoyancy is a valuable predictor of academic performance among high school students. Teachers and educators can use this knowledge to help students develop their academic buoyancy and improve their academic performance.

Marilyn A Marquez, Allie Nadelson, Maria Magraner, Luis J Haddock, Jorge A Fortun Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USACorrespondence: Jorge A Fortun, Email jfortun@med.miami.eduBackground and Objective: To evaluate the use of dynamic infrared (IR) imaging as a tool for the objective evaluation of symptomatic vitreous floaters and to correlate it with the patient symptomatology.Study Design/Materials and Methods: Retrospective study that examined 66 eyes of 44 patients with symptomatic and asymptomatic vitreous opacities. Patients were imaged using the Heidelberg Spectralis dynamic infrared (IR) image in video mode to record the vitreous movements and shadow artifacts within 30 degrees of the center of the macula. Patients were also asked how symptomatic their vitreous floaters were from absent to severe. After reviewing IR videos and OCT, a grading system was created to evaluate the floaters and a masked reader was asked to evaluate the videos and OCT based on the grading system created.Results: A total of 66 eyes were identified and examined with the IR videos, 50 were symptomatic, and 16 were asymptomatic. After masked review and analysis of the IR videos, there were 4 characteristics that correlated with the patient’s symptoms: size, location, movement, and density of obscuration of the OCT B Scan by the vitreous opacity. A table with grading of these characteristics was created to analyze how symptomatic patients were. A masked grader was asked to grade the videos and OCT using the grading system created. A positive correlation was found between the masked grader and the symptoms of patients. (0.70039; p < 0.00001).Conclusion: Dynamic IR video capture of vitreous opacities is a new imaging technique that can qualitatively assess vitreous opacities in a way that correlates to a patient’s symptoms. This imaging modality can provide a qualitative assessment of the patient’s severity of symptoms based on the location, density, and movement of the visualized vitreous opacities in the imaged video.Keywords: floaters, infrared imaging, vitreous opacities, vitreous gel, myodesopsias

BACKGROUND: Ciliary dysfunction underlies the pathogenesis of both heterotaxy syndrome and primary ciliary dyskinesia (PCD), often with overlapping genetic variants. OBJECTIVE: This case series aims to describe genetic testing and postoperative outcomes for infants with heterotaxy-associated congenital heart disease (H-CHD) with pathogenic variants in genes associated with ciliary structure or function. METHODS: Infants who underwent surgery for H-CHD between 2017 and 2022 were included in this single-center review. The results of genetic testing, microarray or sequencing-based tests, were reviewed. Baseline clinical data and postoperative outcomes are summarized for individuals with variants in ciliary genes. RESULTS: Of 32 infants who underwent surgery, 12 had sequencing-based testing. A genetic variant associated with ciliopathy was reported in 10 of 12 infants (83%), 3 (25%) were diagnostic of PCD and 2 (17%) were considered possibly diagnostic. Infants with variants in ciliary genes had high prevalence of postoperative respiratory complications, however a relationship between genetic test results and respiratory complications could not be proven. All infants with a genetic diagnosis of PCD showed clinical symptoms of PCD on follow-up. CONCLUSIONS: Sequencing-based testing has high detection rate for PCD in infants with H-CHD and may be valuable given their increased risk of respiratory complications after surgery.

OBJECTIVE In the management of diabetic ketoacidosis (DKA), the standard of care is to administer insulin glargine after ketoacidosis has resolved and the patient is transitioning from intravenous (IV) insulin to subcutaneous insulin; however, there is evidence to suggest that earlier administration of insulin glargine may accelerate resolution of ketoacidosis. The objective of this research is to determine the efficacy of early subcutaneous insulin glargine on time to resolution of ketoacidosis in children with moderate to severe DKA. METHODS This retrospective chart review evaluated children age 2 to 21 years old admitted for moderate to severe DKA who received insulin glargine within 6 hours of hospital admission (early insulin glargine) compared with those who received insulin glargine greater than 6 hours from admission (late insulin glargine). The primary outcome was duration of time the patient received IV insulin. RESULTS A total of 190 patients were included. The median time on IV insulin was lower in patients who received early insulin glargine compared with those who received late insulin glargine (17.0 [IQR, 14–22.8] vs 22.9 hours [IQR, 4.3–29.3]; p = 0.0006). Resolution of DKA was faster in patients who received early insulin glargine compared with those who received late insulin glargine (median, 13.0 [IQR, 9.8–16.8] vs 18.2 hours [IQR, 12.5–27.6]; p = 0.005). Length of pediatric intensive care unit (PICU) and hospital stay and incidences of hypoglycemia and hypokalemia were similar between the 2 groups. CONCLUSIONS Children with moderate to severe DKA who received early insulin glargine had a significantly lower time on IV insulin, as well as significantly faster time to resolution of DKA when compared with those who received late insulin glargine. There were no significant differences observed in hospital stay and rates of hypoglycemia and hypokalemia.

The 5G ecosystem is comprised of the cellular 5G System, as well as a managed and orchestrated infrastructure providing virtualized network and service functions. The automotive industry with its stringent requirements for connected vehicles is a promising and yet challenging consumer of such 5G ecosystem. Deployment of service instances at distributed cloud resources of cellular network infrastructure edges enables localized low-latency access to these services from moving vehicles but comes along with challenges, such as the need for fast recon-figuration of the distributed deployment according to mobility pattern and associated service and resource demand. In this paper, we investigate a solution for the collaborative orchestration of services for Connected, Cooperative and Automated Mobility (CCAM) within such 5G ecosystem. A key objective is the service continuity for a highly dynamic automotive scenario, achieved by the associated management and orchestration of these services in distributed edge clouds. The proposed solution leverages a multi-tier orchestration system as well as localized management and protocol operations for collaborative edge resources. By means of both analytical and experimental evaluations, the paper draws conclusions on the gain in accelerating orchestration decisions and enforcements, while balancing associated protocol and computational load over the highly distributed and multi-layered orchestration system.

Background: Congestion is central to the pathophysiology of heart failure (HF); thus, tracking congestion is crucial for the management of patients with HF. In this study we aimed to compare changes in inferior vena cava diameter (IVCD) with venous pressure following manipulation of volume status during ultrafiltration in patients with cardiac dysfunction. Methods and Results: Patients with stable hemodialysis and with systolic or diastolic dysfunction were studied. Central venous pressure (CVP) and peripheral venous pressure (PVP) were measured before and after hemodialysis. IVCD and PVP were measured simultaneously just before dialysis, 3 times during dialysis and immediately after dialysis. Changes in IVCD and PVP were compared at each timepoint with ultrafiltration volumes. We analyzed 30 hemodialysis sessions from 20 patients. PVP was validated as a surrogate for CVP. Mean ultrafiltration volume was 2102 ± 667 mL. IVCD discriminated better ultrafiltration volumes ≤ 500 mL or ≤ 750 mL than PVP (AUC 0.80 vs 0.62, and 0.80 vs 0.56, respectively; both P< 0.01). IVCD appeared to track better ultrafiltration volume (P< 0.01) and hemoconcentration (P< 0.05) than PVP. Changes in IVCD were of greater magnitude than those of PVP (average change from predialysis: -58 ± 30% vs -28 ± 21%; P< 0.001). Conclusions: In patients undergoing ultrafiltration, changes in IVCD tracked changes in volume status better than venous pressure.

We examined the impact of statins on protein kinase D (PKD) activation by G protein-coupled receptor (GPCR) agonists. Treatment of intestinal IEC-18 cells with cerivastatin inhibited PKD autophosphorylation at Ser916 induced by angiotensin II (ANG II) or vasopressin in a dose-dependent manner with half-maximal inhibition at 0.2 µM. Cerivastatin treatment inhibited PKD activation stimulated by these agonists for different times (5–60 min) and blunted HDAC5 phosphorylation, a substrate of PKD. Other lipophilic statins, including simvastatin, atorvastatin, and fluvastatin also prevented PKD activation in a dose-dependent manner. Using IEC-18 cell lines expressing PKD1 tagged with EGFP (enhanced green fluorescent protein), cerivastatin or simvastatin blocked GPCR-mediated PKD1-EGFP translocation to the plasma membrane and its subsequent nuclear accumulation. Similar results were obtained in IEC-18 cells expressing PKD3-EGFP. Mechanistically, statins inhibited agonist-dependent PKD activation rather than acting directly on PKD catalytic activity since exposure to cerivastatin or simvastatin did not impair PKD autophosphorylation or PKD1-EGFP membrane translocation in response to phorbol dibutyrate, which bypasses GPCRs and directly stimulates PKC and PKD. Furthermore, cerivastatin did not inhibit recombinant PKD activity determined via an in vitro kinase assay. Using enteroids generated from intestinal crypt-derived epithelial cells from PKD1 transgenic mice as a model of intestinal regeneration, we show that statins oppose PKD1-mediated increase in enteroid area, complexity (number of crypt-like buds), and DNA synthesis. Our results revealed a previously unappreciated inhibitory effect of statins on receptor-mediated PKD activation and in opposing the growth-promoting effects of PKD1 on intestinal epithelial cells.

En este trabajo se determinaron los factores que influyen en la calidad de sueño de los estudiantes de ingeniería, mediante un estudio descriptivo y trasversal. Se empleó una muestra aleatoria de 930 estudiantes de ingeniería eléctrica (124), mecánica (184), civil (281), industrial (164) y química (177). Se utilizó el cuestionario auto aplicable de Índice de Calidad de Sueño de Pittsburg que valora siete componentes hipotéticos, añadiendo al análisis algunas variables socioeconómicas. Se observó que un número importante de estudiantes duermen menos de 8 horas, además se pudo confirmar que la calidad del sueño afecta el desempeño académico ocasionando necesidades médicas, también se pudo constatar que las situaciones socioeconómicas, la carrera, el sexo, la edad y el lugar de procedencia son factores determinantes en la calidad de sueño.

We evaluate the association of familial factors and suicidality among transgender adults in the U.S. by estimating the odds of lifetime suicide ideation and attempt using the 2015 U.S. Transgender Survey. Predictors include family support, family rejection, and specific experiences related to both. About 79% of sample respondents have experienced suicidal ideation and nearly 43% have made a suicide attempt. The predicted probability of suicide attempt is 0.35 for those with no family rejection experiences, 0.75 for those who have had all five experiences in our models. Rejection predicts both outcomes and experiences of rejection have a cumulative impact.

Los colegios novohispanos siempre han sido un tema poco difundido en la historia, pues siempre se suele indagar sobre aquellos cuya estructura aún sigue en pie. Uno de los más importantes fue en su tiempo el Colegio de San Juan de Letrán, investigar sobre él es útil para entender cómo fue la transición durante los últimos años del periodo colonial a los primeros años del México inde- pendiente, pues se pasó de una educación impartida por estudiosos eclesiásticos a una educación ofrecida por estudiosos profesionales, elemento que nos ayudará a comprender el proceso de la reconfiguración del orden letrado en esos años y valorar en su justa dimensión una de las etapas previas de la educación en México.