Early Incorporation to Palliative Care (EPC) in Patients With Advanced Non-Small Cell Lung Cancer: The PACO Randomized Clinical Trial.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience a considerable disease burden, evident in symptomatic and psychological spheres. Advanced cancer represents a complex scenario for patients and the healthcare team. Early palliative care (EPC) has been proven as a clinically meaningful strategy in this context by several randomized trials but not in a resource-limited setting. This study aimed to evaluate the effect of EPC compared with standard oncological care (SOC) in patients with metastatic NSCLC in Mexico. MATERIALS AND METHODS: A prospective, randomized clinical trial was conducted at Instituto Nacional de Cancerologia in Mexico. All patients had histologically confirmed metastatic NSCLC without previous treatment. Patients were randomly assigned (1:1) to receive SOC or SOC + EPC. The EPC group was introduced to the palliative care team at baseline after randomization, which was integrated by psychologists, bachelor's in nutrition, specialized nurses, and physicians. Patients randomized to this arm had programmed visits to meet with the team at baseline and through the 2nd, 4th-, and 6th cycles thereafter. The primary endpoint was overall survival (OS); secondary outcomes included quality of life (QoL), anxiety and depression, and symptom intensity. They were assessed using the instruments EORTC QLQ-C30 questionnaire, Edmonton Symptom Assessment Scale (ESAS), and the Hospital Anxiety and Depression Scale (HADS) (clinicaltrials.gov [NCT01631565]). Questionnaires were completed at baseline, at 2nd, 4th, and 6th cycles of treatment. RESULTS: Between March 2012 and June 2015, 201 patients were assessed for eligibility and 146 were enrolled and allocated to receive EPC (73) or SOC (73). Median OS for patients in the EPC vs SOC arm was 18.1 months (95% CI, 7.9-28.4) and 10.5 months (95% CI, 4.7-16.2) (P = .029). Having a poor performance status (HR 1.7 [1.2-2.5]; P = .004) and allocation to the control group (HR 1.5 [1.03-2.3]; P = .034) were independently associated with a worse OS. Those patients with a global QoL > 70 at baseline had a better OS if they were In the EPC arm (38.7 months (95% CI, 9.9-67.6) vs SOC 21.4 months (95% CI, 12.4-30.3)). Mean QoL had a numerical improvement in patients allocated to EPC after 6 cycles of follow-up, nonetheless this difference was not statistically significant (55.1 ±â€…23.7 vs 56.9 ±â€…25.3; P = .753). There were no significant differences in anxiety and depression at all study points. CONCLUSIONS: EPC is associated with a significant improvement in OS, although, we observed that the greatest benefit of providing EPC was observed in those with a global QoL > 70 at baseline. This study did not identify significant changes in terms of QoL or symptom burden between the study groups after follow-up. Evidence robustly suggests that EPC should be considered part of the multidisciplinary treatment of metastatic NSCLC patients since diagnosis. According to our study, EPC can be implemented in low- or middle-income countries (LMIC).

T-line Hernia Mesh Repairs of Large Umbilical Hernias: Technique and Short-term Outcomes.

Background: The T-line hernia mesh is a synthetic, polypropylene mesh specifically designed to prevent anchor point failure by evenly distributing tension through mesh suture extensions. This case series illustrates the first clinical application of the T-line mesh for umbilical hernia repair (UHR). Methods: This study is a retrospective, consecutive cases series of all adult patients presenting to a single surgeon with symptomatic umbilical hernia requiring surgical repair using the T-line hernia mesh. Patient demographics, surgical details, and 30-day postoperative complications were collected. Descriptive statistics were computed in Microsoft Excel (Redmond, Va.). Results: Three patients presented for UHR. All three patients were obese with mean body mass index of 37.5 ±â€…6.6. Two patients were former smokers, and two had presented after hernia recurrence. The average defect size was 80.1 cm2 ± 94.0 cm2. Two patients had UHR with onlay mesh placement, whereas one had a transversus abdominus release followed by retrorectus mesh placement. The average mesh size was 192.3 cm2 ± 82.5 cm2. All three cases were classified as clean. There were no intraoperative complications. No patients experienced 30-day postoperative complications or recurrence. Conclusions: We present a case series of three patients presenting with large, symptomatic umbilical hernias who underwent UHR with T-line hernia mesh reinforcement without short term complications or hernia recurrence at last follow-up.

Risk factors associated with glomerular filtration rate in Mexican adults with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is related to glomerular filtration rate (GFR) impairment, which is one of the main causes of chronic kidney disease. The objective of this study was to identify the risk factors related to GFR in Mexican adults with T2DM, using a validated multiple linear regression model (MLRM), with emphasis in body adiposity, glycemic control, duration of the diabetes and other relevant risk factors. MATERIALS AND METHODS: A cross-sectional, analytical, and observational study was carried out in 252 adults with a previous diagnosis of T2DM. Body mass index (BMI) and waist circumference (WC) were determined and a fasting blood sample was collected for glucose, creatinine and HbA1c determinations. GFR was calculated with the Cockcroft-Gault equation adjusted for body surface area. Four MLRM were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptions of the linear regression model. RESULTS: The average age of the participants was 60 ±â€¯12 years, 62.3% of them were women. GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely. Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (ß = 1.31), male sex (ß = -6.01), duration of T2DM (ß = -0.57), arterial hypertension (ß = -6.53) and age (ß = -1.45) were simultaneously and significantly related to the GFR. CONCLUSIONS: Older age, male sex, longer duration of T2DM and the presence of arterial hypertension were associated with a decrease in the GFR; BMI and WC were directly associated. No effect of glucose and HbA1c on GFR was observed.

DIAGNOSTIC PERFORMANCE OF BLOOD ANALYTES FOR THE DIAGNOSIS OF RENAL DISEASE IN BLACK-FOOTED FERRETS (MUSTELA NIGRIPES) AT THE PHOENIX ZOO (2001-2020).

Renal disease is an important cause of morbidity and mortality in managed black-footed ferrets (BFF; Mustela nigripes).4,6,12 The objectives of this study were to establish reference intervals for blood analytes of clinically normal BFF (1-2 yr old), summarize the frequency of various renal histopathologic findings in a managed population of BFF, assess the diagnostic performance of blood analytes and urine specific gravity (USG) for the diagnosis of renal disease, and assess if comorbidities or age affects the performance of these analytes in diagnosing renal disease. Reference intervals were established using a cohort (n = 35) of clinically normal, young adult BFF. Postmortem records for all BFF at the Phoenix Zoo between 2001 and 2020 were reviewed, and those with available blood analyte data within 2 wk of death were included (n = 89). Ferrets were placed into one of three groups, based on the organ location of histopathologic abnormalities following necropsy: renal disease as the primary change; those with renal disease and at least one other affected major organ system; or absence of abnormalities in the kidneys. In ferrets with substantial renal changes, the primary diagnosis was amyloidosis (29 of 39; 74.4%). Creatinine, blood urea nitrogen, phosphorus (P), calcium (Ca), Ca:P ratio, USG, globulins, and cholesterol were the best-performing analytes for the diagnosis of renal disease, with an area under the curve of at least 0.90 (95% CI $ 0.80, 1.00). Serum renal markers were within reference intervals in BFF that died without histologic evidence of renal disease. Several blood analytes were significantly affected by age in animals that died of renal disease. This study provides reference intervals for blood analytes in young adult clinically normal BFF and illustrates the clinical utility for the diagnosis of renal disease in this species, particularly creatinine, USG, and P.

Safe nanomaterials: from their use, application, and disposal to regulations.

Nanomaterials are structures with a wide range of applications in the medical, pharmaceutical, food, textile, and electronic industries, reaching more customers worldwide. As a relatively new technological field, the information about the associated risk of nanomaterials in environmental and human health must be addressed and consolidated to develop accurate legislations, frameworks, and guidelines to standardise their use in any field. This review aims to display and context the global applications of nanomaterials, their final disposal, as well as the perspective of the current efforts formulated by various countries (including Mexico and Latin American countries), international official departments and organisations directed to implement regulations on nanomaterials, nanotechnology, and nanoscience matters. In addition, the compiled information includes the tools, initiatives, and strategies to develop regulatory frameworks, such as life cycle assessments, risk assessments, technical tools, and biological models to evaluate their effects on living organisms. Finally, the authors point out the importance of implementing global regulations to promote nanotechnological research according to a precautionary principle focused on an environmental and health protection approach to ensure the use and application of nanotechnologies safely, and responsibly.

Protein digestibility and ACE inhibitory activity of fermented flours in older adults and standard gastrointestinal simulation.

Consumption of essential amino acids responsible for muscle protein synthesis is important in preventing sarcopenia among older individuals. This population may experience gastrointestinal disorders that inhibit protein digestibility, making it crucial to address. Therefore, solid-state fermentation (SSF) using Pleurotus ostreatus and air drying has been suggested as a means of improving the protein digestibility of lentils and quinoa. SSF combined with air drying at 70 °C resulted in a slight increase in protein hydrolysis compared to unfermented samples. SSF was found to boost the proportion of small peptides to 35 %. Following digestion, SSF and drying yielded bioactive peptides of 1400 and 450 Da, with a range of 11 % to 28 %, respectively, and peptides < 190 Da making up 60 % of the total. SSF promoted valine, leucine, and isoleucine generation; however, hot air drying reduced free amino acids due to the amino acid-reducing sugar bonding but was never lower than the initial content of its unfermented counterpart. Furthermore, SSF and drying at 70 °C improved the release of hydrophobic amino acids (>70 mg/g dry basis) and negatively charged amino acids (>20 mg/g dry basis) in lentils during digestion. The SSF samples exhibited lower angiotensin converting enzyme (ACE) inhibitory activity, ≤35 %, compared to unfermented flours after digestion. However, the ACE inhibitory activity increased in SSF-dried samples, in part because of melanoidins generated during drying. Finally, lower values of protein digestibility and thus smaller peptides, amino acid profile, and ACE inhibitory activity of fermented flours were found in the older adult digestion model.

Long-Term Outcomes of Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction: A Study from Mexico City.

Although primary percutaneous coronary intervention (pPCI) is the treatment of choice in ST-elevation myocardial infarction (STEMI), challenges may arise in accessing this intervention for certain geodemographic groups. Pharmacoinvasive strategy (PIs) has demonstrated comparable outcomes when delays in pPCI are anticipated, but real-world data on long-term outcomes are limited. The aim of the present study was to compare long-term outcomes among real-world patients with STEMI who underwent either PIs or pPCI. This was a prospective registry including patients with STEMI who received reperfusion during the first 12 hours from symptom onset. The primary objective was cardiovascular mortality at 12 months according to the reperfusion strategy (pPCI vs PIs) and major cardiovascular events (cardiogenic shock, recurrent myocardial infarction, and congestive heart failure), and Bleeding Academic Research Consortium type 3 to 5 bleeding events were also evaluated. A total of 799 patients with STEMI were included; 49.1% underwent pPCI and 50.9% received PIs. Patients in the PIs group presented with more heart failure on admission (Killip-Kimbal >I 48.1 vs 39.7, p = 0.02) and had a lower proportion of pre-existing heart failure (0.2% vs 1.8%, p = 0.02) and atrial fibrillation (0.25% vs 1.2%, p = 0.02). No statistically significant difference was observed in cardiovascular mortality at the 12-month follow-up (hazard ratio for PIs 0.74, 95% confidence interval 0.42 to 1.30, log-rank p = 0.30) according to the reperfusion strategy used. The composite of major cardiovascular events (hazard ratio for PIs 0.98, 95% confidence interval 0.75 to 1.29, p = 0.92) and Bleeding Academic Research Consortium type 3 to 5 bleeding rates were also comparable. A low socioeconomic status, Killip-Kimball >2, age >60 years, and admission creatinine >2.0 mg/100 ml were predictors of the composite end point after multivariate analysis. In conclusion, this prospective real-world registry provides additional support that long-term major cardiovascular outcomes and bleeding are not different between patients who underwent PIs versus primary PCI.

Determinants of Vitamin D Status in Healthy Young Adults from Mexico City.

BACKGROUND AND AIMS: Vitamin D deficiency is a global health problem. The determinants of this deficiency have not been evaluated in developing countries such as Mexico. Thus, this study aimed to determine vitamin D intake and sun exposure and its relationship with plasma concentrations of 25-hydroxyvitamin D -25(OH)D- in young adults from Mexico City. METHODS: One hundred fifty five urban adult subjects were enrolled during 2017 and 2018. Sociodemographic, anthropometric, and clinical data, vitamin D intake, and sun exposure habits were collected. Plasma concentrations of 25(OH)D were also determined. RESULTS: The proportion of vitamin D deficiency was significantly higher in women than in men (65.7 vs. 43.4%, p = 0.012). The overall median dietary vitamin D intake was 112 IU/d (less than 20% of the recommended daily intake; RDI). 25-hydroxyvitamin D correlated directly with vitamin D intake, sun exposure score, waist-to-hip ratio, and age; an inverse significant association was found with body fat percentage. A multiple regression analysis was performed; simultaneous and significant (p <0.01) effects of sun exposure score, dietary vitamin D, the season of the year (spring-summer vs. fall-winter), and age were observed on 25(OH)D levels. CONCLUSION: High rates of vitamin D deficiency and insufficiency were observed in young adults from Mexico City. According to the RDI of this vitamin, its consumption, assessed by a 24 h multi-step nutritional questionnaire, was significantly low. A linear multiple regression model identified several predictors of plasma 25(OH)D concentrations. This multiple regression model was statistically validated.

The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Intraobserver and interobserver agreement of 8 segmental reflexes in healthy dogs.

BACKGROUND: No available literature supports the claim that the patellar and withdrawal (flexor) reflexes are the only reliable segmental reflexes in dogs. OBJECTIVE: Measure intra- and interobserver agreement of 8 segmental reflexes in dogs without clinical evidence of orthopedic or neurologic disease. ANIMALS: One-hundred and one client- or staff-owned dogs between 1 and 10 years of age with no clinical evidence of orthopedic disease, myelopathy, or neuromuscular disease. METHODS: Descriptive study. The intraobserver proportion of agreement (%) of responses to selected segmental reflexes in right versus left limbs by 3 observers was calculated and reported. The interobserver agreement of 2 observers of responses to selected reflexes was estimated by calculating proportions of agreement, kappa values, and 95% confidence intervals. A segmental reflex with an acceptable agreement was defined as that with a proportion of agreement ≥90% and a Kappa value ≥0.61 in both limbs. RESULTS: The intraobserver proportion of agreement for all 3 observers was high (≥95%) for the extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes. Between observers 1 and 3 and observers 2 and 3, the interobserver proportion of agreement was high (≥ 92%) for the extensor carpi radialis (κ 0.66, not determined [ND]), withdrawal (both limbs, κ ND), patellar (κ ND), and cranial tibial reflexes (κ ND). CONCLUSIONS AND CLINICAL IMPORTANCE: The extensor carpi radialis, withdrawal, patellar, and cranial tibial reflexes had a higher proportion of agreement and kappa values between 2 observers.

Estado nutricional y medidas antropométricas en escolares Zapotecas y no Zapotecas de Oaxaca, México / Nutritional status and anthropometric measurements in Zapotec and non-Zapoteca schoolchildren from Oaxaca, Mexico

Introducción: Los grupos indígenas se enfrentan a la discriminación y exclusión, lo que genera inequidades en el ámbito de la salud. Además, son nutricionalmente vulnerables, lo que afecta su potencial de crecimiento y desarrollo en comparación con población no indígena. Objetivo: comparar el estado nutricional y medidas antropométricas entre escolares zapotecas y no zapotecas de una región de Oaxaca, México. Material y métodos: estudio descriptivo trasversal en una muestra representativa de 477 escolares de 8 a 11 años de un municipio de Oaxaca. Se dividió a la población en zapoteco (Zap+) y no zapoteco (Zap-). Se obtuvo el peso, talla, circunferencia de cintura, circunferencia de brazo y el pliegue tricipital. Se calculó el IMC para la edad, el índice cintura-talla e indicadores del componente graso y muscular del brazo. Se utilizó la prueba chi cuadrada y exacta de Fisher para diferencias proporcionales Resultados: El 51,5% de escolares fue Zap+ y se reportó una alta prevalencia de sobrepeso y obesidad de 33,7%. Las niñas Zap+ presentaron mayor prevalencia de desmedro (p=0,032) y los niños Zap+ presentaron menor % área grasa de brazo (0,004). Entre niños y niñas Zap-, los niños presentaron bajo peso (p=0,040) y musculatura reducida (p=0,003), mientras que las niñas presentaron mayor proporción grasa arriba del promedio (p=<0,001). Los niños Zap- presentaron mayor prevalencia de desmedro en comparación con los Zap+ (p=0,022). Esta diferencia se mantuvo hasta los 11 años (p=0,007). Se observó que las niñas Zap+ de 11 años presentaron una menor musculatura (p=0.001) y mayor riesgo cardiovascular (p=0,032) en comparación con las Zap-. Conclusiones: Se observaron cambios seculares positivos en niños Zap+ reflejados en una mayor talla que las niñas Zap+ y niños Zap-, y una tendencia al aumento del IMC y riesgo cardiovascular en las niñas Zap+ lo cual podría reflejar una posible transición nutricional.(AU)

Introduction: Indigenous groups face discrimination andexclusion, which generates inequities in the field of health. Inaddition, they are nutritionally vulnerable, which affects theirgrowth and development potential compared to the non-in-digenous population. Objective: to compare the nutritional status and anthro-pometric measurements between Zapotec and non-Zapotecschoolchildren from a region of Oaxaca, Mexico. Material and methods: cross-sectional descriptive studyin a sample of 477 schoolchildren aged 8 to 11 from a mu-nicipality in Oaxaca. The population was divided into Zapotec(Zap+) and non-Zapotec (Zap-). Weight, height, waist cir-cumference, arm circumference and triceps fold were meas-ured. Anthropometric indicators and the fatty and muscularcomponent of the arm were calculated. A comparative analy-sis of nutritional status and body composition was performedbetween Zap+ and Zap- using chi square and Fisher’s exacttest. A p value <0.05 was considered significant. Results: 51.5% of schoolchildren were Zap+ and a highprevalence of overweight and obesity of 33.7% was reported.Zap+ girls had a higher prevalence of wasting (p=0.032) andZap+ boys had a lower % arm fat area (0.004). Among Zap-boys and girls, boys had low weight (p=0.040) and reducedmusculature (p=0.003), while girls had a higher proportion offat above average (p=<0.001). Zap- children had a higherprevalence of stunting compared to Zap+ children (p=0.022).It was observed that 11-year-old Zap+ girls had less muscle(p=0.001) and a higher cardiovascular risk (p=0.032) com-pared to Zap- girls. Conclusions: Positive secular changes were observed inZap+ boys, reflected in greater height than Zap- boys, and atrend in increasing BMI and cardiovascular risk in Zap+ girls,which could reflect a possible nutritional transition.(AU)

Analysing Early Diagnosis Strategies for HIV Infection: A Retrospective Study of Missed Diagnostic Opportunities.

Early diagnosis of a Human Immunodeficiency Virus (HIV)-infected person represents a cornerstone of HIV prevention, treatment, and care. Numerous publications have developed recommendations where HIV serology is indicated to reduce missed diagnostic opportunities (MDOs). This retrospective study analyses new HIV infection diagnoses and the relationship between late diagnosis (LD)/advanced HIV disease (AHD), baseline characteristics, and MDOs. Sociodemographic data and data related to contact with the health system in the 5 years before diagnosis were collected. Most of the 273 diagnoses were made in primary care (48.5%). Approximately 50.5% and 34.4% had LD and AHD criteria, respectively. Female sex was associated with a higher incidence of LD. Persons infected through the heterosexual route and those at an older age had a higher risk for LD and AHD. People with previous HIV serology presented a lower percentage of LD and AHD. In total, 10% of the health contact instances were classified as MDOs, mostly occurring in primary care. A significant increase in the median of MDOs was observed in patients with LD/AHD. Female sex and hepatitis C virus co-infection were associated with an increase in the number of MDOs. The high percentage of LD and AHD and the significant number of MDOs show that the current screening system should be improved.

Efficacy of treatment of equine anhidrosis with acupuncture and Chinese herbs is low but higher in treated horses compared with placebo.

OBJECTIVE: To assess the therapeutic efficacy of acupuncture in combination with Chinese herbs for treatment of horses affected with anhidrosis. ANIMALS: 44 horses affected with anhidrosis for up to 3 years' duration were enrolled. Inclusion required both compatible clinical signs and results of a quantitative intradermal terbutaline sweat test. METHODS: Study horses were randomly allocated into 2 groups. Group 1 (n = 19) was treated with daily Chinese herbs and 4 weekly acupuncture sessions. Group 2 (n = 25) was given daily hay powder as a placebo and 4 weekly sham acupuncture sessions. Horses were tested by quantitative intradermal terbutaline sweat test within 2 days after treatment completion and again 4 weeks following treatment. RESULTS: Terbutaline-induced sweat responses (mg) were not different between groups within 2 days and 4 weeks after treatment. Two days after treatment, ratios of sweat responses (compared to baseline) were higher (P < .05) in the treatment group compared to the placebo group at terbutaline concentrations of 1.0, 100, and 1,000 µg/mL. The number of horses responding to treatment was higher in the treatment group (5/19 [26%]), compared to horses in the placebo group (1/25 [4%]) for 1 of 5 terbutaline concentrations 2 days (10 µg/mL) or 4 weeks (0.1 µg/mL) after treatment. CLINICAL RELEVANCE: Ratios of sweat responses were higher in treatment horses 2 days after treatment, compared to baseline, but not 4 weeks later. The efficacy of a traditional Chinese veterinary medicine protocol for anhidrosis treatment with acupuncture and Chinese herbs was low but higher in treated horses compared with placebo.

Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis.

Familial melanoma is defined as melanoma occurring in two or more first-degree relatives by the WHO. Germline mutations are isolated in a subset of them. It is well known that CDKN2A is the most frequently mutated high-risk gene in familial melanoma, however, the prognosis it confers to patients who carry its mutations is still controversial. This review aims to assess whether germline mutations imply a worse prognosis in patients with familial melanoma. A systematic review and meta-analysis were conducted by searching the electronic databases PubMed/MEDLINE, EMBASE, and Cochrane Library. Data from 3 independent populations were eventually included in the meta-analysis, involving 291 cases and 57 416 controls. The results of this systematic review and meta-analysis suggest that there is a tendency for patients with germline mutations in the CDKN2A gene to have a worse overall survival (HR = 1.30, 95% CI = 0.99-1.69, P  = 0.05) and melanoma-specific survival (HR = 1.5, 95% CI = 0.97-2.31, P  = 0.07). Carrier patients would not only have more incidence of melanoma and a higher risk of a second melanoma, but they also seem to have a worse prognosis. The inclusion of gene panel testing in clinical practice and the collaboration within consortia are needed to provide further evidence on the prognosis of these patients.

Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.

Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.

Enfoque estratégico para la acreditación de la especialidad de Higiene y Epidemiología en Villa Clara / Strategic approach for the accreditation of the Hygiene and Epidemiology specialty in Villa Clara

La epidemiología es una ciencia básica de la Salud Pública porque sus fundamentos científicos permiten la toma de decisiones en los problemas de salud. Para controlar la calidad de la formación de los profesionales y perfeccionarla, se aplica el sistema de acreditación de escenarios docentes, proceso de gran importancia que garantiza la calidad del pregrado y el posgrado. En la Universidad de Ciencias Médicas de Villa Clara se realizó dicho proceso en la especialidad de Higiene y Epidemiología, fue utilizada la autoevaluación estratégica del escenario laboral como actividad previa. El interés de los autores es exponer el método seguido para cumplir con los requerimientos establecidos. Con la aplicación de esta matriz estratégica para lograr el estado deseado en el proceso docente de la especialidad de Higiene y Epidemiología en la Universidad de Ciencias Médicas de Villa Clara se logró una evaluación de excelente.

Epidemiology is a basic science of Public Health because its scientific foundations make possible decision-making regarding health problems. To control the training quality for professionals and improve it, the accreditation system for teaching scenarios is applied, a very important process that guarantees the quality of undergraduate and postgraduate training. At the University of Medical Sciences of Villa Clara, in the specialty of Hygiene and Epidemiology, this process was carried out; the strategic self-assessment of the work scenario as a prior activity, was used. To expose the method followed to comply with the established requirements, is the aim of the authors. By using this strategic matrix to achieve the desired state in the teaching process of the specialty of Hygiene and Epidemiology at the University of Medical Sciences of Villa Clara, an excellent evaluation was achieved.

Parturition and Neonatal Parameters of Three Species of Rhinoceros under Managed Care in the United States.

Rhinoceros species range from near threatened to critically endangered due to habitat loss and poaching. A sustainable ex situ breeding population is critically important to maintain genetic diversity and help ensure the survival of the species; however, not all populations under human care are self-sustaining. While rhinoceros reproductive physiology and pathology have been well studied, there is still a paucity of information describing the normal parameters of parturition and neonatal landmarks. Using video recordings, medical records, and keeper logs, we reviewed and compared data regarding the parturition of three rhinoceros species (black rhinoceros (BR) (Diceros bicornis), n = 4; greater one-horned rhinoceros (GOHR) (Rhinoceros unicornis), n = 21; and southern white rhinoceros (SWR) (Ceratotherium simum simum), n = 22) managed under human care in the United States. Using equine parameters as a model for comparison, we compiled the following data: the signs of impending parturition, durations of the parturition phases, calving presentation, frequency of dystocia or stillbirth, and time from birth to neonatal landmarks. Data from 47 births, including 26 videos, were examined. The durations of parturition phases I, II, and III had median lengths of 153 min (n = 18), 28 min (n = 21), and 205 min (n = 15), respectively. Anterior presentation of the calf was observed in 59% births, whereas posterior presentation occurred in 41% births. Posterior calving presentation was associated with a longer phase II of parturition (p = 0.04), although more data are needed to determine whether the posterior presentation of the calf carries a higher risk for stillbirth. Most (83%) stillbirths occurred in GOHR, indicating that this species might be at a higher risk for stillbirth compared to SWR (17%) (p = 0.07). The median time from birth to the calf standing was longer in the GOHR (64 min) compared to the SWR (30 min) (p = 0.02). Detailed descriptions of the parturition parameters and neonatal landmarks in rhinoceros will aid facilities with rhinoceros breeding programs to recognize abnormalities in the parturient or post-partum periods and guide indications for veterinary intervention.

Testicular Germ Cell Tumors in Children and Adolescents Treated With Bleomycin, Etoposide, and Cisplatin (BEP) Protocol: A Survival Analysis.

BACKGROUND: Germ cell tumors (GCTs) represent a diverse group of rare neoplasms that vary in location, histology, and clinical presentation. This study focuses on the clinical outcomes and survival rates of children and adolescents treated with the bleomycin, etoposide, and cisplatin (BEP) protocol. METHODS: This observational study evaluated children under 18 years diagnosed with testicular germ cell tumors and treated with the BEP protocol from January 2008 to December 2018. We employed descriptive analysis and used the Kaplan-Meier method to calculate event-free survival (EFS) and overall survival rates. RESULTS: The study included 32 patients with an average age of 9.8 years (SD ± 6.7). The primary reason for consultation was a testicular mass. The classification of patients was E-I for 14 patients (44%) and E-III and E-IV for nine patients (28%). Endodermal sinus tumors and mixed germ cell tumors were the most commonly identified histological types. With a median follow-up of 7.8 years (95% confidence interval {CI}: 5.9-9.6), the event-free survival was 63.7%. The overall survival at a median follow-up of 9.1 years (95% CI: 7.5-10.7) was 76.1%. CONCLUSION: The BEP chemotherapy regimen offers promising results for treating testicular germ cell tumors in children and adolescents, characterized by its low toxicity and minimal late side effects. However, patients older than 11 years displayed more adverse histological indicators, advanced disease stages, and higher relapse and mortality rates.