Implementing precision oncology in Latin America to improve patient outcomes: the status quo and a call to action for key stakeholders and decision-makers.

Background: The advent of precision oncology (PO) has revolutionised diagnostic and follow up strategies and improved clinical outcomes for cancer patients. However, socio-economic inequalities in the level of implementation of PO in different countries is a prevailing issue. To improve this situation, the Latin America Patients Academy has gathered the recommendations of healthcare professionals and social civil members experienced in cancer management from Mexico, Guatemala, Costa Rica, Dominican Republic, Panama, Colombia, Chile, Ecuador, Peru and Argentina regarding the areas that need to be prioritised to improve the access to PO in Latin American (LATAM) countries. Methods: This manuscript is the culmination of a series of educational campaigns and panel discussion aimed at improving the implementations of PO in LATAM that took place from June 2021 to January 2022. The status of PO in Latin America: the level of PO implementation is generally low with some exceptions. The number of clinical trials and articles published with keywords related to PO from LATAM countries is drastically lower than in Europe and the United States. Despite sharing many complex challenges, progress is taking place in some countries in the region. Focus areas defined by the expert panel: The expert panel determined the areas of PO that should be improved by LATAM countries to improve its implementation through cancer care plans, educational programs and collaborative strategies. These initiatives should increase awareness about PO in the region and eventually improve cancer control in the region.

Lysophosphatidic acid receptor LPA1 trafficking and interaction with Rab proteins, as evidenced by Förster resonance energy transfer.

LPA1 internalization to endosomes was studied employing Förster Resonance Energy Transfer (FRET) in cells coexpressing the mCherry-lysophosphatidic acid LPA1 receptors and distinct eGFP-tagged Rab proteins. Lysophosphatidic acid (LPA)-induced internalization was rapid and decreased afterward: phorbol myristate acetate (PMA) action was slower and sustained. LPA stimulated LPA1-Rab5 interaction rapidly but transiently, whereas PMA action was rapid but sustained. Expression of a Rab5 dominant-negative mutant blocked LPA1-Rab5 interaction and receptor internalization. LPA-induced LPA1-Rab9 interaction was only observed at 60 min, and LPA1-Rab7 interaction after 5 min with LPA and after 60 min with PMA. LPA triggered immediate but transient rapid recycling (i.e., LPA1-Rab4 interaction), whereas PMA action was slower but sustained. Agonist-induced slow recycling (LPA1-Rab11 interaction) increased at 15 min and remained at this level, whereas PMA action showed early and late peaks. Our results indicate that LPA1 receptor internalization varies with the stimuli.

Glycemic control, treatment and complications in patients with type 1 diabetes amongst healthcare settings in Mexico.

AIMS: Type 1 diabetes (T1D) is a growing chronic disease. Evidence of whether the healthcare setting affects management and glycemic control is scarce. We evaluate outcomes in patients with T1D in private and public healthcare settings in Mexico, registered in the National T1D Registry in Mexico (RENACED-DT1). METHODS: Biochemical parameters, diabetes education, and treatment were analyzed considering the data registered in the last visit. Development of chronic complications was determined during follow-up. RESULTS: We included 1,603 patients; 71.5% (n = 1,146) registered in the public system, and 28.5% (n = 457) in a private institution. Patients in the public setting had higher HbA1c (8.6%, IQR: 7.3%-10.5% vs 7.7%, IQR: 7.0%-8.8%; p < 0.001). Indicators of diabetes education, glucose monitoring, and use of insulin-pumps were lower in the public setting. Patients in the public setting were at higher risk of diabetic chronic kidney disease, retinopathy, and neuropathy. Diabetes knowledge was a mediator between type of healthcare setting and the likelihood of achieving glycemic control. CONCLUSIONS: Patients registered in public healthcare settings have an adverse metabolic profile and higher risk of complications. Social factors need to be addressed in order to implement multidisciplinary measures focused on diabetes education for patients with T1D in Mexico.

Type 1 diabetes care in mexico: an analysis of the renaced-dt1 national registry

Background: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). Objective: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. Methods: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. Results: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). Conclusions: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.

Type 1 Diabetes Care in Mexico: An Analysis of the RENACED-DT1 National Registry.

BACKGROUND: Information regarding diagnosis, treatment, and follow-up of patients with type 1 diabetes (PWT1D) in Mexico is limited. We developed an on-line platform Registro Nacional de Pacientes con Diabetes Tipo 1 (RENACED-DT1). OBJECTIVE: The objective of the study was to describe the characteristics and healthcare of PWT1D registered in RENACED-DT1. METHODS: Analyses of 965 PWT1D from July 2014 to January 2018 in different endocrinology clinics around Mexico. RESULTS: Sixty-one percent were female with median age of 21 years, age at diagnosis 11 years, and disease duration at inclusion 8.2 years. Treatment regimen was basal-bolus in 61% and insulin-pumps in 21% (mainly in the private sector); 33.3% with self-monitoring of blood-glucose (SMBG) ≥4 times/day. Mean HbA1c at last follow-up was 8.7 ± 2.1% (72±23 mmol/mol), 18% had HbA1c < 7% (53 mmol/mol), and 35% > 9% (75 mmol/mol). SMBG ≥ 4 times/day was associated with HbA1c < 7%. Time since diagnosis > 10 years, female sex, BMI ≥ 30 kg/m2, SMBG < 4 times/day, and any hypoglycemia were associated with microvascular complications (p < 0.05). CONCLUSIONS: Percentage of patients achieving HbA1c < 7% is low; increased blood glucose monitoring is associated with better glycemic control. The achievement of optimal glycemic control must be increased to reduce the incidence of chronic complications and improve quality of life in PWT1D.

Lateral transorbital canthopexy using a silicone tube in patients with paralytic ectropion.

PURPOSE: We describe the efficacy of lateral transorbital canthopexy using a silicone tube in managing severe paralytic ectropion. METHODS: Patients with paralytic ectropion involving at least two-third of lower eyelid length and scleral exposure of 3 mm or more were considered. A silicone prosthetic was inserted during canthopexy. RESULTS: Lateral transorbital canthopexy using a silicone tube was performed on 10 eyelids in nine patients. All patients had corneal surface abnormalities. Scleral exposure resolved completely in three cases. At 8-month follow-up, residual scleral exposure of 1 mm and 2 mm persisted in n = 6 and n = 1 cases, respectively. CONCLUSIONS: Lateral transorbital canthopexy using a silicone tube is an effective therapeutic option for paralytic ectropion, facilitating both functional and cosmetic results that proved durable over time.

Visualization and Quantification of Electrochemical H2 Bubble Nucleation at Pt, Au, and MoS2 Substrates.

Electrolytic gas evolution is a significant phenomenon in many electrochemical technologies from water splitting, chloralkali process to fuel cells. Although it is known that gas evolution may substantially affect the ohmic resistance and mass transfer, studies focusing on the electrochemistry of individual bubbles are critical but also challenging. Here, we report an approach using scanning electrochemical cell microscopy (SECCM) with a single channel pipet to quantitatively study individual gas bubble nucleation on different electrode substrates, including conventional polycrystalline Pt and Au films, as well as the most interesting two-dimensional semiconductor MoS2. Due to the confinement effect of the pipet, well-defined peak-shaped voltammetric features associated with single bubble nucleation and growth are consistently observed. From stochastic bubble nucleation measurement and finite element simulation, the surface H2 concentration corresponding to bubble nucleation is estimated to be ∼218, 137, and 157 mM, with critical nuclei contact angles of ∼156°, ∼161°, and ∼160° at polycrystalline Pt, Au, and MoS2 substrates, respectively. We further demonstrated the surface faceting at polycrystalline Pt is not specifically correlated with the bubble nucleation behavior.

Rise in Murine Typhus in Galveston County, Texas, USA, 2018.

Murine typhus, an undifferentiated febrile illness caused by Rickettsia typhi, is increasing in prevalence and distribution throughout Texas. In 2018, a total of 40 cases of murine typhus were reported in Galveston County. This increase, unprecedented since the 1940s, highlights the importance of awareness by physicians and public health officials.

Influence of Echeveria gibbiflora DC aqueous crude extract on mouse sperm energy metabolism and calcium-dependent channels.

ETHNOPHARMACOLOGY RELEVANCE: In traditional Mexican medicine, Echeveria gibbiflora DC has been used as a vaginal post-coital rinse to prevent pregnancy. The aqueous crude extract (OBACE) induces sperm immobilization/agglutination and a hypotonic-like effect, likely attributed to the high concentration of calcium bis-(hydrogen-1-malate) hexahydrate [Ca2+ (C4H5O5)2•6H2O]. Likewise, OBACE impedes the increase of [Ca2+]i during capacitation. AIM OF THE STUDY: Evaluate the effect of OBACE on sperm energy metabolism and the underlying mechanism of action on sperm-specific channel. MATERIAL AND METHODS: In vitro, we quantified the mouse sperm immobilization effect and the antifertility potential of OBACE. The energetic metabolism status was also evaluated by assessing the ATP levels, general mitochondrial activity, mitochondrial membrane potential, and enzymatic activity of three key enzymes of energy metabolism. Furthermore, the effect of the ion efflux of Cl- and K+, as well as the pHi, were investigated in order to elucidate which channel is suitable to perform an in silico study. RESULTS: Total and progressive motility notably decreased, as did fertility rates. ATP levels, mitochondrial activity and membrane potential were reduced. Furthermore, the activities of the three enzymes decreased. Neither Cl- or K+ channels activities were affected at low concentrations of OBACE; nevertheless, pHi did not alkalinize. Finally, an in silico analysis was performed between the Catsper channel and calcium bis-(hydrogen-1-malate) hexahydrate, which showed a possible blockade of this sperm cation channel. CONCLUSION: The results were useful to elucidate the effect of OBACE and to propose it as a future male contraceptive.

Morphological Evolution of Vertically Standing Molybdenum Disulfide Nanosheets by Chemical Vapor Deposition.

In this study, we demonstrated the chemical vapor deposition (CVD) of vertically standing molybdenum disulfide (MoS2) nanosheets, with an unconventional combination of molybdenum hexacarbonyl (Mo(CO)6) and 1,2-ethanedithiol (C2H6S2) as the novel kind of Mo and S precursors respectively. The effect of the distance between the precursor’s outlet and substrates (denoted as d) on the growth characteristics of MoS2, including surface morphology and nanosheet structure, was investigated. Meanwhile, the relationship between the structure characteristics of MoS2 nanosheets and their catalytic performance for hydrogen evolution reaction (HER) was elucidated. The formation of vertically standing nanosheets was analyzed and verified by means of an extrusion growth model. The crystallinity, average length, and average depth between peak and valley (Rz) of MoS2 nanosheets differed depending on the spatial location of the substrate. Good crystalized MoS2 nanosheets grown at d = 5.5 cm with the largest average length of 440 nm, and the highest Rz of 162 nm contributed to a better HER performance, with a respective Tafel slope and exchange current density of 138.9 mV/decade, and 22.6 μA/cm² for raw data (127.8 mV/decade and 19.3 μA/cm² for iR-corrected data).

[Evaluation of cardiovascular risk factors in obesity before and after bariatric surgery]. / Evaluación de factores de riesgo cardiovascular antes y después de cirugía bariátrica.

BACKGROUND: Mexico has one of the highest prevalences of severe obesity worldwide. Mortality in those patients may be as high as 90% mainly due to cardiovascular disease. Despite Framingham score has been validated in the Mexican population, it only predicts cardiovascular risk at 10 years. Meanwhile ASCVD10 score could evaluate risk at 10 years and through lifetime. None of these scores have been used for cardiovascular risk assessment in Mexican patients with severe obesity. METHODS: We conducted a quasi-experimental (before/ after) study with 109 patients with severe obesity, assessed prevalence of comorbidities, performed anthropometric and biochemical evaluations before and a year after bariatric surgery. With these results we calculated Framingham and ASCVD10 scores and compared them. RESULTS: Patients had a mean age of 45.3 ± 10.1 years, 70% female, 79% underwent laparoscopic Roux-en-Y gastric bypass. We observed weight decrease at each evaluation point after surgery, independently of the surgical procedure. All biochemical parameters improved. Framingham score decreased from 9.4% to 5.9%, frequency of patients classified as high-risk decreased from 25% to 11%. ASCVD10 score decreased from 4.1% to 2.5%, patients classified as high-risk decreased from 28% to 16%. Tobacco use was the most important factor involved in cardiovascular risk. CONCLUSIONS: Cardiovascular risk at 10-years and lifetime decreased as soon as one year after surgery as assessed through Framingham and ASCVD scores.

INTRODUCCIÓN: México posee una de las más altas prevalencias de obesidad severa en el mundo. La mortalidad por causas cardiovasculares en estos pacientes alcanza el 90%. Existen distintas escalas para valorar el riesgo, como la escala de Framingham que evalúa a 10 años, y la ASCVD10 que evalúa a 10 años y a lo largo de la vida. Ninguna se ha usado para evaluar el riesgo cardiovascular en mexicanos con obesidad severa antes y después de la cirugía bariátrica. MÉTODOS: se efectuó un estudio cuasiexperimental con 109 pacientes con obesidad severa, con evaluación antropométrica y bioquímica, antes y un año después de la cirugía bariátrica. Se obtuvo el puntaje de riesgo con las escalas de Framingham y ASCVD10. RESULTADOS: la mediana de edad fue 45.3 ± 10.1 años, 70% eran mujeres, en 79% se realizó bypass laparoscópico con Y de Roux. Hubo disminución de peso en cada evaluación posterior a la cirugía, independientemente del procedimiento, y mejoría en todos los parámetros bioquímicos. El riesgo evaluado por Framingham disminuyó de 9.4 a 5.9%, el porcentaje de pacientes de "alto riesgo" disminuyó de 25 a 11%; con respecto al riesgo evaluado por ASCVD10 se redujo de 4.1 a 2.5%, con porcentaje de pacientes de alto riesgo que disminuyó de 28 a 16%. El tabaquismo fue el mayor determinante de riesgo cardiovascular. CONCLUSIONES: el riesgo cardiovascular evaluado por ambas escalas disminuyó un año después de la cirugía bariátrica.

Uso de una escala clínica predictiva para el diagnóstico de meningitis bacteriana en pediatría: [revisión] / Utility of a predictive score for the diagnosis of bacterial meningitis in children: [review]

La difícil interpretación de los hallazgos sugestivos de meningitis bacteriana y viral en el líquido cefalorraquídeo con frecuencia imposibilita su diferenciación. Por décadas, los investigadores han intentado crear escalas predictivas que permitan resolver tal disyuntiva. El objetivo del presente trabajo es determinar la validez y seguridad de una escala clínica predictiva para el diagnóstico de meningitis bacteriana en Pediatría. Realizamos un estudio retrospectivo, transversal, de evaluación de una prueba diagnóstica en una muestra de pacientes con edades entre 29 días y 12 años, egresados con diagnóstico de meningitis entre enero de 1992 y diciembre de 2006, del Deparatmento de Pediatría del Hospital "Dr. Jesús Yerena", ubicado en Caracas, Venezuela. aplicamos una escala clínica predictiva y calculamos su sensibilidad, especificidad, valores predictivos y razones de verosimilitud para el diagnóstico de meningitis bacteriana. La muestra estuvo conformada por 41 pacientes. Predomino el sexo masculino (n=29; 70,73 por ciento). El grupo etareo más afectado fue el de los lactantes menores (26=; 63,41 por ciento). Se identificaron 14 meningitis bacterianas y 27 asépticas. Mediante la escala clínica predictiva se clasificaron 31 meningitis como de alto riesgo de meningitis v¡bacteriana y 10 como de bajo riesgo. La sensibilidad y valor predictivo negativo fueron de 100 por ciento. La escala clínica predictiva resultó ser válida y segura para descartar meningitis bacteriana.

The overlapping of finding suggestive of bacterial or viral meningitis in cerebrospinal fluid makes it difficult to differentiate one of another. For decades, investigators have attempted to create clinical prediction scores to resolve such disjunctive. The objetive of this investigation was to determine the validity and safety of a clinical prediction score for the diagnosis of bacterial meningitis in childhood. We perfomed a retrospective, transversal, diagnosis test evaluation study of a sample of patients between 29 days to 12 years of age, dischanged from January 1992 to December 2006, with diagnosis of meningitis, from the Pediatrics Department of Dr. Jesús Yerena Hospital, in Caracas, Venezuela. The clinical prediction score was applied. We evaluated its validity and safety with the calculation of sensibility, specificity, predictive values and likelihood ratios for the diagnosis of bacterial meningitis. A total of 41 patients were included. Male gender was more common (n=29; 70,73%). The infant age group was predominant (n=26; 63,41%). We identified 14 bacterial meningitis and 27 aseptic meningitis. With the clinical predictin score, 31 meningitis were classified as high risk of bacterial meningitis and 10 as low risk. The sensibility and the negative value were 100%. The clinical prediction score applied resulted to be valid and safe for identifying patients without bacterial meningitis.