Estrés laboral y desempeño laboral en el Instituto Regional de Enfermedades Neoplásicas (IREN) - Concepción Huancayo, 2022

El proyecto tuvo como finalidad determinar la relación entre el estrés laboral y el desempeño laboral en la institución Regional de Enfermedades Neoplásicas (IREN) – Concepción Huancayo en 2022. Se empleó un enfoque descriptivo-correlacional sin experimentación, con una muestra de 285 trabajadores. Los datos se recopilaron a través del cuestionario de estrés laboral de la OIT-OMS y el cuestionario de desempeño laboral. Se obtuvo como resultado que no existe concordancia y significancia entre el estrés y el desempeño laboral en esta institución. Sin embargo, se identificaron correlaciones entre el estrés laboral y ciertas dimensiones del desempeño laboral, como la orientación hacia los resultados, la capacidad profesional y la identidad e iniciativa. En conclusión, el estrés y el desempeño laboral son independientes entre sí en este contexto específico. Se recomienda que la dirección de la organización implemente un plan de desarrollo personal para abordar el estrés laboral y mejorar la calidad del trabajo de su personal evaluado

Crosstalk between the p190-B RhoGAP and IGF signaling pathways is required for embryonic mammary bud development

AbstractP190-B RhoGAP (p190-B, also known as ARHGAP5) has been shown to play an essential role in invasion of the terminal end buds (TEBs) into the surrounding fat pad during mammary gland ductal morphogenesis. Here we report that embryos with a homozygous p190-B gene deletion exhibit major defects in embryonic mammary bud development. Overall, p190-B-deficient buds were smaller in size, contained fewer cells, and displayed characteristics of impaired mesenchymal proliferation and differentiation. Consistent with the reported effects of p190-B deletion on IGF-1R signaling, IGF-1R-deficient embryos also displayed a similar small mammary bud phenotype. However, unlike the p190-B-deficient embryos, the IGF-1R-deficient embryos exhibited decreased epithelial proliferation and did not display mesenchymal defects. Because both IGF and p190-B signaling affect IRS-1/2, we examined IRS-1/2 double knockout embryonic mammary buds. These embryos displayed major defects similar to the p190-B-deficient embryos including smaller bud size. Importantly, like the p190-B-deficient buds, proliferation of the IRS-1/2-deficient mesenchyme was impaired. These results indicate that IGF signaling through p190-B and IRS proteins is critical for mammary bud formation and ensuing epithelial–mesenchymal interactions necessary to sustain mammary bud morphogenesis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Liderazgo directivo y desempeño docente en la Institución Educativa Inicial Nuestra Señora De La Esperanza Del Distrito Tambopata Puerto Maldonado - 2016

En este estudio se investigó el “Liderazgo directivo y desempeño docente en la I.E inicial nuestra Señora de la Esperanza de Puerto Maldonado - 2016”. La investigación tiene como propósito principal determinar la relación que existe entre los estilos de liderazgo directivo y el desempeño docente en el nivel inicial nuestra Señora de la Esperanza de Puerto Maldonado - 2016. Tanto la encuesta sobre liderazgo directivo como la ficha de evaluación del desempeño docente fueron aplicadas sobre toda la población conformada por 25 profesores, sin criterios de exclusión. Se trató de obtener resultados de correlación entre los aspectos estudiadosTesi

A Phase I Trial of PI3Kαδ Inhibitor Copanlisib in Combination with Nivolumab in Patients with Richter's Transformation (RT) or Transformed Non-Hodgkin Lymphoma (tNHL)

Abstract Background. Despite advances in targeted and cellular therapy, outcomes among patients with RT and tNHL remain dismal. Copanlisib (COPA) is a selective, small molecule, PI3K inhibitor which preferentially targets the p110αδ isoforms . COPA has shown clinical efficacy in NHL and is an approved therapy for follicular lymphoma (FL). Nivolumab is a PD-1 antagonist which has demonstrated activity in Hodgkin lymphoma as well as NHL. Furthermore, combined targeting of PI3K and PD-1 has demonstrated synergy in pre-clinical lymphoma models. Here we report initial results of a phase 1 study of COPA in combination with nivolumab in patients with R/R RT or tNHL (NCT03884998). Methods. This ongoing multicenter, open-label, phase I, investigator-sponsored study is enrolling patients with RT or tNHL, age ≥18 years, whose disease had relapsed or was refractory to ≥1 prior line of therapy. The phase I portion of the study followed a standard 3+3 design with three planned dose levels of COPA administered IV (dose level [DL]1 - 45 mg on days 1, 8 and 15; DL2 - 60 mg on days 1, 8 and 15; DL "-1" - 45 mg on days 1 and 15 of a 28-day cycle). Nivolumab 240 mg was given IV on days 1 and 15. Patients received up to 24 cycles of therapy. The primary study objective was to evaluate the maximum tolerated dose (MTD) of the combination; secondary objectives included preliminary measures of efficacy by Lugano criteria including PET/CT scans. Exploratory objectives included pharmacodynamic endpoints. Dose limiting toxicities (DLT) were defined as grade ≥4 hematologic &amp;gt; 7 days or grade ≥3 non-hematologic toxicities. Results. Of the eleven patients enrolled, 8 had RT and 3 had transformed FL (tFL); 91% (10/11) were men. Median age was 70 (43-77) years, 82% (9/11) had an ECOG performance status ≤1. Patients had received a median of 3 prior lines of therapy (range, 1-8), including three patients (1 RT, 2 FL) who had undergone CAR T cell therapy. Eight patients were treated at DL1 (45 mg COPA), of which 2 patients did not complete the DLT period due to rapidly progressive disease and were replaced. No DLTs were observed at this dose level. At DL2 (60 mg COPA), three DLTs (grade 4 febrile neutropenia and grade 4 thrombocytopenia in another patient) were observed among the three patients treated. Therefore, the MTD and recommended phase 2 dose (RP2D) of COPA in combination with nivolumab was determined to be 45 mg on days 1, 8, 15. The most common treatment-related adverse events (AEs, any grade) were anemia and neutropenia (Table 1). Five pts discontinued therapy due to progressive disease; one due to intercurrent infection (coccidiomycosis, unrelated to study drugs), two due to DLTs noted above. Three patients remain on treatment. Among the seven efficacy-evaluable patients who completed at least one cycle of therapy, median time on treatment was 2 months (range, 2-9 months). Of these, four patients achieved a response per the investigators' assessment (tFL: 2 partial responses; RT: 1 complete response and 1 partial response). Efficacy assessment is ongoing and will be reported at the meeting. Discussion. We identified COPA 45 mg IV on days 1, 8 and 15 as the MTD/RP2D in combination with nivolumab in patients with R/R RT and tFL. This combination was well-tolerated at the MTD/RP2D, and the study is currently enrolling patients in an expansion cohort to further characterize the efficacy of this regimen. Figure 1 Figure 1. Disclosures Shouse: Beigene Pharmaceuticals: Honoraria; Kite Pharmaceuticals: Speakers Bureau. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Popplewell: Pfizer: Other: Travel; Novartis: Other: Travel; Hoffman La Roche: Other: Food. Kittai: Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy; Abbvie: Consultancy. Davids: MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; AbbVie: Consultancy; BeiGene: Consultancy; Merck: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Eli Lilly and Company: Consultancy; BMS: Consultancy, Research Funding; Janssen: Consultancy; Celgene: Consultancy; Astra-Zeneca: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Research to Practice: Consultancy; Verastem: Consultancy, Research Funding; Takeda: Consultancy; MEI Pharma: Consultancy; TG Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Danilov: Genentech: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Rigel Pharm: Honoraria; Takeda Oncology: Research Funding; Bayer Oncology: Consultancy, Honoraria, Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Research Funding. </jats:sec

Latino parent acculturation stress: Longitudinal effects on family functioning and youth emotional and behavioral health

Latino parents can experience acculturation stressors, and according to the Family Stress Model (FSM), parent stress can influence youth mental health and substance use by negatively affecting family functioning. To understand how acculturation stressors come together and unfold over time to influence youth mental health and substance use outcomes, the current study investigated the trajectory of a latent parent acculturation stress factor and its influence on youth mental health and substance use via parent-and youth-reported family functioning. Data came from a 6-wave, school-based survey with 302 recent (<5 years) immigrant Latino parents (74% mothers, Mage = 41.09 years) and their adolescents (47% female, Mage = 14.51 years). Parents' reports of discrimination, negative context of reception, and acculturative stress loaded onto a latent factor of acculturation stress at each of the first 4 time points. Earlier levels of and increases in parent acculturation stress predicted worse youth-reported family functioning. Additionally, earlier levels of parent acculturation stress predicted worse parent-reported family functioning and increases in parent acculturation stress predicted better parent-reported family functioning. While youth-reported positive family functioning predicted higher self-esteem, lower symptoms of depression, and lower aggressive and rule-breaking behavior in youth, parent-reported family positive functioning predicted lower youth alcohol and cigarette use. Findings highlight the need for Latino youth preventive interventions to target parent acculturation stress and family functioning. (PsycINFO Database Recor

Trajectories of Cultural Stressors and Effects on Mental Health and Substance Use Among Hispanic Immigrant Adolescents

PURPOSE: We sought to determine the extent to which initial levels and over-time trajectories of cultural stressors (discrimination, negative context of reception, and bicultural stress) predicted well-being, internalizing symptoms, conduct problems, and health risk behaviors among recently immigrated Hispanic adolescents. Addressing this research objective involved creating a latent factor for cultural stressors, establishing invariance for this factor over time, estimating a growth curve for this factor over time, and examining the effects of initial levels (intercepts) and trajectories (slopes) of cultural stressors on adolescent outcomes. METHODS: A sample of 302 recently immigrated Hispanic adolescents in Miami (Mdn 1 year in the US at baseline) and Los Angeles (Mdn 3 years in the US at baseline) was recruited from public schools and assessed 6 times over a 3-year period. RESULTS: Perceived discrimination, context of reception, and bicultural stress loaded onto a latent factor at each of the first five timepoints. A growth curve conducted on this factor over the first five timepoints significantly predicted lower self-esteem and optimism, more depressive symptoms, greater aggressive behavior and rule breaking, and increased likelihood of drunkenness and marijuana use. CONCLUSIONS: The present results may be important in designing interventions for Hispanic immigrant children and adolescents, including those within the current wave of unaccompanied child migrants. Results indicate targeting cultural stressors in interventions may have potential to improve well-being and decrease externalizing behaviors and substance use within this population