Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru.

BACKGROUND: Limited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older. METHODS: An ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with each factor, and the number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the PAF and confidence intervals. The number of new cancer cases and deaths attributed to each risk factor was determined by multiplying the number of cases and deaths in each gender by the PAF of each risk factor. FINDINGS: In Peru, 38.5% of new cases (34.5% in men and 42% in women) and 43.4% of cancer-related deaths (43.4% in men and 43.4% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,308 (10,439 in men and 14,869 in women) and the number of deaths attributable to cancer was 14,839 (6,953 in men and 7,886 in women). The predominant modifiable risk factors contributing to the highest number of cases and deaths were HPV infection (4,563 cases, 2,409 deaths), current tobacco use (3,348 cases, 2,180 deaths), and helicobacter pylori infection (2,677 cases, 1,873 deaths). Among the risk factors, oncogenic infections constituted the group with the highest PAF (16.6% for cases, 19.2% for deaths) followed by other unhealthy lifestyle factors (14.2% for cases, 16.7% for deaths), tobacco (7.2% for cases, 7.2% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSIONS: Prior to the COVID-19 pandemic, 38.5% of cancer cases and 43.4% of cancer-related deaths in Peru were linked to modifiable risk factors in the population of 15 years old and older. Most preventable cancer cases and deaths were related to oncogenic infections, primarily caused by HPV and helicobacter pylori, followed by tobacco and obesity.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Exploring Influences on Environmental Stewardship of Fishing Communities in Fisheries Management in the Philippines.

Fisheries compliance has been explored conceptually and empirically in numerous contexts but in many fisheries, compliance with rules is not sufficient to return to sustainable levels of effort. Failing to understand the context and what drives fishers to behave the way they do, has the potential to misdirect investments. The authors present a conceptual model of fisheries ecosystem stewardship (FES) that expands upon fisheries compliance with the addition of moral obligation for fishing communities. This paper uses household survey data from fishing communities in three marine key biodiversity areas (MKBA) in the Philippines to test part of the FES model using logistic regression and multiple regression analysis with empirical data to test the model. Data shows that apart from the respondents' location (i.e., which MKBA is adjacent to their community), knowledge of laws protecting coastal/marine resources was the most important predictor of environmental stewardship, followed by support for limiting fishing effort and knowledge of illegal fishing. Individual decisions about if and how-to fish are influenced by the economic context and available livelihood opportunities. However, the moral obligation to "do the right thing" is equally, if not more important to consider for fisheries ecosystem stewardship in fishing communities.

Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of ß-Glucocerebrosidase.

ß-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the misfolded protein and increase delivery of degradation-prone mutant GCase to the lysosome is a strategy under active investigation. Here, we describe the first use of fragment-based drug discovery (FBDD) to identify pharmacological chaperones of GCase. The fragment hits were identified by using X-ray crystallography and biophysical techniques. This work led to the discovery of a series of compounds that bind GCase with nM potency and positively modulate GCase activity in cells.

Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2).

The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.

Heavy-enzyme kinetic isotope effects on proton transfer in alanine racemase.

The catalytic effects of perdeuterating the pyridoxal phosphate-dependent enzyme alanine racemase from Geobacillus stearothermophilus are reported. The mass of the heavy perdeuterated form is ~5.5% greater than that of the protiated form, causing kinetic isotope effects (KIEs) of ~1.3 on k(cat) and k(cat)/K(M) for both L- and D-alanine. These values increase when Cα-deuterated alanine is used as the substrate. The heavy-enzyme KIEs of ~3 on k(cat)/K(M) with deuterated substrates are greater than the product of the individual heavy-enzyme and primary substrate KIEs. This breakdown of the rule of the geometric mean is likely due to coupled motion between the protein and the proton-transfer reaction coordinate in the rate-limiting step. These data implicate a direct role for protein vibrational motions in barrier crossing for proton-transfer steps in alanine racemase.

Factors Associated with Symptoms of Depression among People with Obesity: Analysis of a 3-Year-Peruvian National Survey.

INTRODUCTION: Obesity and depression contribute to the global burden of economic cost, morbidity, and mortality. Nevertheless, not all people with obesity develop depression. OBJECTIVE: To determine the factors associated with depressive symptoms among people aged 15 or older with obesity from the National Demographic and Family Health Survey (ENDES in Spanish 2019-2021). METHODS: Cross-sectional analytical study. The outcome of interest was the presence of depressive symptoms, assessed using the Patient Health Questionnaire-9 (PHQ-9). Crude (cPR) and adjusted (aPR) prevalence ratios were estimated using GLM Poisson distribution with robust variance estimates. RESULTS: The prevalence of depression symptoms was 6.97%. In the multivariate analysis, a statistically significant association was found between depressive symptoms and female sex (PRa: 2.59; 95% CI 1.95-3.43); mountain region (PRa: 1.51; 95% CI 1.18-1.92); wealth index poor (PRa: 1.37; 95% CI 1.05-1.79, medium (PRa: 1.49; 95% CI 1.11-2.02), and rich (PRa: 1.65; 95% CI 1.21-2.26); daily tobacco use (PRa: 2.05, 95% CI 1.09-3.87); physical disability (PRa: 1.96, 95% CI 1.07-3.57); and a history of arterial hypertension (PRa: 2.05; 95% CI 1.63-2.55). CONCLUSION: There are several sociodemographic factors (such as being female and living in the Andean region) and individual factors (daily use of tobacco and history of hypertension) associated with depressive symptoms in Peruvian inhabitants aged 15 or older with obesity. In this study, the COVID-19 pandemic was associated with an increase in depressive symptoms.

The Fruit Intake-Adiposity Paradox: Findings from a Peruvian Cross-Sectional Study.

Due to the increase in obesity worldwide, international organizations have promoted the adoption of a healthy lifestyle, as part of which fruit consumption stands out. However, there are controversies regarding the role of fruit consumption in mitigating this disease. The objective of the present study was to analyze the association between fruit intake and body mass index (BMI) and waist circumference (WC) in a representative sample of Peruvians. This is an analytical cross-sectional study. Secondary data analysis was conducted using information from the Demographic and Health Survey of Peru (2019-2021). The outcome variables were BMI and WC. The exploratory variable was fruit intake, which was expressed in three different presentations: portion, salad, and juice. A generalized linear model of the Gaussian family and identity link function were performed to obtain the crude and adjusted beta coefficients. A total of 98,741 subjects were included in the study. Females comprised 54.4% of the sample. In the multivariate analysis, for each serving of fruit intake, the BMI decreased by 0.15 kg/m2 (ß = -0.15; 95% CI -0.24 to -0.07), while the WC was reduced by 0.40 cm (ß = -0.40; 95% CI -0.52 to -0.27). A negative association between fruit salad intake and WC was found (ß = -0.28; 95% CI -0.56 to -0.01). No statistically significant association between fruit salad intake and BMI was found. In the case of fruit juice, for each glass of juice consumed, the BMI increased by 0.27 kg/m2 (ß = 0.27; 95% CI 0.14 to 0.40), while the WC increased by 0.40 cm (ß = 0.40; 95% CI 0.20 to 0.60). Fruit intake per serving is negatively related to general body adiposity and central fat distribution, while fruit salad intake is negatively related to central distribution adiposity. However, the consumption of fruit in the form of juices is positively associated with a significant increase in BMI and WC.

Ground-state electronic destabilization via hyperconjugation in aspartate aminotransferase.

Binding isotope effects for l-aspartate reacting with the inactive K258A mutant of PLP-dependent aspartate aminotransferase to give a stable external aldimine intermediate are reported. They provide direct evidence for electronic ground-state destabilization via hyperconjugation. The smaller equilibrium isotope effect with deazaPLP-reconstituted K258A indicates that the pyridine nitrogen plays an important role in labilizing the Cα-H bond.

Psychosocial implications of avatar use in supporting therapy for depression.

Help4Mood is a novel intervention to support the treatment of depressive disorder using an embodied communicative agent (Avatar) to engage the user with therapy tasks. We conducted 10 focus groups with patients and mental health professionals, in the UK, Spain and Romania, in order to explore issues around usability and contextual fit. Emergent themes related to the design and use of Avatars indicated the value of configurability for optimising personalisation and perceived trustworthiness; the importance of supplementing rather than replacing face-to-face interaction, and perceptions of the agent as therapeutic ally or supportive friend. The use of Avatars in psychotherapy is relatively new and its acceptability, value and risks are unknown. These results indicate that users wish to engage with Avatars that meet their personal preferences and fit appropriate role expectations. The perception of Avatar as colleague or friend raises conceptual and ethical issues which merit further research.

Rendimiento diagnóstico de once indicadores para resistencia a la insulina en una muestra de pobladores peruanos

Introducción: La resistencia a la insulina (RI) es una de las principales causas del desarrollo de patologías crónicas. Es indispensable su detección temprana, por ello es importante estudiar métodos más asequibles y menos costosos como los biomarcadores. Objetivo: Determinar la precisión diagnóstica de once biomarcadores para RI en una muestra de pobladores peruanos. Metodología: Estudio de pruebas diagnósticas. Análisis de base de datos secundario del estudio PERU MIGRANT. Para medir RI se utilizó como referencia la evaluación del modelo homeostático (HOMA-IR) ≥ 2,8. Los biomarcadores se basaron en la ratio de lípidos, los indicadores de lípido visceral, los indicadores con triglicéridos y glucosa (TyG), y los indicadores con cintura abdominal. Para la precisión se utilizó el análisis de la curva de características operativas del receptor y el área bajo la curva (AUC) con sus respectivos intervalos de confianza al 95% (IC95%). Resultados: Se estudió a 938 participantes. La prevalencia de RI fue del 9,91%. En relación con el análisis ROC, el índice TyG - índice de masa corporal (TyG - IMC) tuvo el mayor AUC, tanto en hombres: AUC=0,85 (0,81 - 0,90), corte=241,55; sens=92,5 (79,6 - 98,4) y esp=78,3 (73,9 - 82,2); como en mujeres: AUC=0,81 (0,76 - 0,85), corte=258,77; sens=79,2 (70,3 - 86,5) y esp= 82,1 (78,0 - 85,8). Discusión: Según los datos analizados, el índice TyG-IMC es el mejor indicador para medir RI. Es un índice simple que se puede tomar de manera rutinaria en la práctica clínica diaria. Es conveniente añadir futuros estudios prospectivos que confirmen su capacidad predictiva.

Introduction: Insulin resistance (IR) is one of the main causes of chronic disease. Early detection is essential, which is why it is important to study more affordable and less expensive methods, such as biomarkers. Objective: To determine the diagnostic accuracy of 11 biomarkers of IR in a sample of Peruvian residents. Method: diagnostic tests. Secondary Database Analysis of the PERU-MIGRANT Study. To measure RI, a homeostatic model evaluation (HOMA-IR) ≥ 2.8 was used as a reference. Biomarkers were based on the lipid ratio, visceral lipid indicators, indicators of triglycerides and glucose (TyG), and indicators of abdominal waist. For precision, the receiver operating characteristic curve and area under the curve (AUC) with their respective 95% confidence intervals (95%CI) were used. Results: A total of 938 participants were studied. The prevalence of IR was 9.91%. In relation to the ROC analysis, the TyG index - body mass index (TyG - BMI) had the highest AUC, both in men: AUC=0.85 (0.81 - 0.90), cut-off=241.55; sens=92.5 (79.6 - 98.4) and sp=78.3 (73.9 - 82.2); as in women: AUC=0.81 (0.76 - 0.85), cut-off=258.77; sens=79.2 (70.3 - 86.5) and esp= 82.1 (78.0 - 85.8). Discussion: According to the data analyzed, the TyG-IMC index is the best indicator for measuring IR. It is a simple index that can be routinely used in clinical practice. Future prospective studies are needed to confirm its predictive capacity.

Swimming and Gendered Vulnerabilities: Evidence from the Northern and Central Philippines.

Men and women's vulnerability to disasters is different and often related, in part, to cultural norms that influence gendered behaviors and abilities. In this study we focus on gender differences in swimming abilities, which, in the case of tsunamis have resulted in far greater female mortality rates. We present results on swimming ability by gender for 940 residents of coastal rural communities in the northern and central Philippines. We also examine cross-generational transmission of swimming abilities to shed light on future vulnerability. Results reveal men are far more likely than women to swim and, importantly, parents who can swim are more likely to have children who can swim. In this way, differences in swimming ability among today's adults may perpetuate vulnerabilities within future generations.

Infecciones intrahospitalarias en el estudiante de medicina / In-Hospital Infections In The Medical Student

Las enfermedades asociadas a la atención en el sector salud es una problemática que no solo implica a los pacientes que ingresan al servicio, si no al personal y a los estudiantes que llevan a cabo sus prácticas en las diferentes instituciones. Las infecciones intrahospitalarias están definidas como: "Enfermedades localizadas o sistémicas que resultan de una reacción adversa consecuente a la exposición a un agente infeccioso o a sus toxinas, sin evidencia que la infección estuviera presente o en periodo de incubación en el momento de la atención" . La falta de conocimientos por parte del personal y estudiantes de las ciencias de la salud que están en contacto con los pacientes, además de la realización de prácticas sanitarias sin tomar en cuenta las medidas de bioseguridad pertinentes son los principales motivos para contraer una infección nosocomial.

The diseases associated with care in the health sector is a problem that not only involves patients who enter the service, but also the staff and students who carry out their practices in the different institutions. In-hospital infections are defined as: "Localized or systemic diseases resulting from an adverse reaction resulting from exposure to an infectious agent or its toxins, with no evidence that the infection was present or in the incubation period at the time of care." The lack of knowledge on the part of the personnel and students of the health sciences that are in contact with the patients, in addition to the realization of sanitary practices without taking into account the pertinent biosecurity measures are the main reasons for contracting a nosocomial infection.

Estudio de Factibilidad para Evaluar la Proporción de Cáncer Atribuible a Factores de Riesgo Modificables en el Perú y Latinoamérica / Feasibility Study To Evaluate The Proportion Of Cancer Attributable To Modifiable Factors Of Risk In Peru And Latin America

Objetivo: Evaluar la factibilidad y validar de la propuesta metodológica para estimar la incidencia y mortalidad por cáncer atribuible a factores de riesgo modificables para el Perú y Latinoamérica. Métodos: Estudio piloto, ecológico a partir de fuentes secundarias. Se buscó y seleccionó los factores de riesgo modificables, prevalencia de exposicion, los riesgos relativos de dichos factores (RR) o una aproximación mediante la razón de posibilidades (OR). La información fue consignada en una ficha de recolección de datos la cual fue validada mediante juicio de expertos. Para el cálculo de la Fracción Atribuible Poblacional (FAP) se ensayó la fórmula planteada por Parkin y se desarrolló un modelo de simulación estadística con el software R. Studio V. 3.6.1. Resultados: En el Perú se cuenta con estudios de prevalencia para la mayoría de factores de riesgo modificables; asimismo, se dispone en Latinoamérica de estudios con estimaciones de OR para varios de los factores; sin embargo hubo que utilizar estudios de los Estados Unidos para los factores restantes. No hallamos estudios nacionales de radiaciones ionizantes ni ultravioleta. Se ensayó la sintaxis del modelo de simulación estadística la cual mostró ser válida y consistente con los resultados de estudios internacionales de FAP encontrándose dentro de los rangos de los estudios publicados. Conclusión: Es factible y viable realizar estudios de FAP de factores de riesgo modificables para cáncer en países de Latinoamérica, particularmente en el Perú, donde se cuenta con la información requerida para su estimación.

Objective: To evaluate the feasibility of the methodological proposal to estimate the incidence and mortality due to cancer attributable to modifiable risk factors for Peru and Latin America. Methods: Pilot study, ecological from secondary sources. Modifiable risk factors, exposure prevalence, relative risks of these factors (RR) or an approximation by means of possibilities ratio (OR) were searched and selected. The information was recorded in a data collection form which was validated by expert judgment. For the calculation of the Population Attributable Fraction (FAP), the formula proposed by Parkin was tested and a statistical simulation model was developed with R. Studio V. 3.6.1 software. Results: In Peru there are prevalence studies for the majority of modifiable risk factors; Likewise, studies with OR estimates for several of the factors are available in Latin America; however, studies from the United States had to be used for the remaining factors. No national studies of ionizing or ultraviolet radiation were found. The syntax of the statistical simulation model was tested, which proved to be valid and consistent with the results of international FAP studies within the ranges of published studies. Conclusion: It is feasible and viable to carry out PAF studies of modifiable risk factors for cancer in Latin American countries, particularly in Peru, where the information required for its estimation is available.

Adaptación y validación de un cuestionario para medir burnout académico en estudiantes de medicina de la universidad Ricardo Palma / Adaptation And Validation Of A Questionnaire To Measure Academic Burnout In Medical University Students

Introducción: Evaluar lLa validez y fiabilidad de un instrumento adaptado al Perú para medir la pre-sencia del Síndrome de Burnout en estudiantes universitarios de la carrera de Medicina Humana en la Universidad Ricardo Palma, tomando como punto de partida el Inventa-rio de Burnout de Maslach - Student Survey (MBI-SS). Métodos: Estudio transversal analítico, con nivel de investigación aplicativo. Se evaluó la validez por análisis de estructura factorial con el método de componentes principales, se apli-caron las pruebas de Kaiser-Meyer Olkin y la rotación Varimax; la confiabilidad por el valor alfa de Cronbach. Resultados: Fueron incluidos 223 estudiantes de la Facultad de Medicina Humana de la Universidad Ricardo Palma, en el periodo noviembre a diciembre del año 2016. La prevalencia de Burnout académico encontrada fue 28,25% (63); La prueba de adecuación de Kaiser-Meyer Olkin tuvo un resultado de 0.813 y la prueba de esfericidad de Barlett de 1007.5 (p<0.000). Se calculó la varianza acumulada explicada por 3 factores fue de 55.4%. El instrumento obtuvo un coeficiente Alfa de Cronbach= 0,794, con correlaciones entre los ítems, Agotamiento Emocional (α= ,855), Cinismo (α=0,623) y Eficacia Académica (α= 0,744). Conclusión: El instrumento adaptado y validado reúne las propiedades psicométricas para ser con-siderado un instrumento útil y fiable inicialmente en estudiantes de medicina humana de la Universidad Ricardo Palma, presentando una adecuada estructura factorial y consis-tencia interna para la determinación del nivel de Síndrome de Burnout Académico.

Introduction: Evaluate the validity and reliability of an instrument adapted to Peru to measure the presence of Burnout Syndrome in university students of the Human Medicine career at the Ricardo Palma University, taking as starting point the Burnout Inventory of Maslach - Student Survey (MBI-SS). Methods: Cross-sectional analytical study, with level of application research. Validity was evaluat-ed by factorial structure analysis with the principal components method, Kaiser-Meyer Olkin tests and Varimax rotation were applied; the reliability by the Cronbach alpha val-ue. Results: 223 students from the Faculty of Human Medicine of the Ricardo Palma University were included, from November to December 2016. The prevalence of academic Burn-out found was 28.25% (63); The Kaiser-Meyer Olkin fitness test had a result of 0.813 and Barlett's sphericity test of 1007.5 (p <0.000). The cumulative variance explained by 3 factors was calculated to be 55.4%. The instrument obtained a Cronbach's Alpha co-efficient = 0.794, with correlations between the items, Emotional Exhaustion (α =, 855), Cynicism (α = 0.623) and Academic Efficiency (α = 0.744). Conclusion: The adapted and validated instrument gathers the psychometric properties to be con-sidered a useful and reliable instrument initially in human medicine students of the Ri-cardo Palma University, presenting an adequate factorial structure and internal con-sistency to determine the level of Academic Burnout Syndrome.