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It is convenient to study complete genome sequences of human respiratory syncytial virus (hRSV) for ongoing genomic characterization and identification of highly transmissible or pathogenic variants. Whole genome sequencing of hRSV has been challenging from respiratory tract specimens with low viral loads. Herein, we describe an amplicon-based protocol for whole genome sequencing of hRSV subgroup A validated with 24 isolates from nasopharyngeal swabs and infected cell cultures, which showed cycle threshold (Ct) values ranging from 10 to 31, as determined by quantitative reverse-transcription polymerase chain reaction. MinION nanopore generated 3200 to 5400 reads per sample to sequence over 93% of the hRSV-A genome. Coverage of each contig ranged from 130× to 200×. Samples with Ct values of 20.9, 25.2, 27.1, 27.7, 28.2, 28.8, and 29.6 led to the sequencing of over 99.0% of the virus genome, indicating high genome coverage even at high Ct values. This protocol enables the identification of hRSV subgroup A genotypes, as primers were designed to target highly conserved regions. Consequently, it holds potential for application in molecular epidemiology and surveillance of this hRSV subgroup.

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Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.

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RESUMEN Se presenta el caso de un paciente varón de 55 años con antecedente de colecistitis aguda, que durante la hospitalización presentó anemia por hemobilia secundaria a un pseudoaneurima de la arteria cistica. Se realizó, como tratamiento de primera elección, embolización con microparticulas de alcohol polivinílico (PVA) de la arteria cistica, logrando detención del sangrado.

SUMMARY We present the case of a 55-year-old male patient with a history of acute cholecystitis who presented during his hospitalization haemobilia due to a pseudoaneurysm of the cystic artery. Embolectomy of the cystic artery with polyvinyl alcohol microparticles was performed stopping the bleeding.

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The aim of this longitudinal study was to determine the effect of an original prevention program (RAPP) on the behavioral and cognitive characteristics of adolescents with high risk for substance consumption. Seventy-six Mexican adolescents 12-15 years old (38 with high risk (HR) and 38 with low risk (LR)) were selected. RAPP was applied for 3 months. Resilience, social skills, attitudes towards substance use, ability to delay a reward, and inhibitory control were assessed in these adolescents, before and after the RAPP intervention. Both groups improved their scores; however, HR achieved greater changes than LR. Findings suggest that HR have behavioral characteristics that can be considered as risk factors for substance consumption (low levels of resilience, low social skills, little family support, positive attitudes towards substance use). RAPP proved to be an effective program for preventing these risk factors for substance use in adolescents.

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A critical biological event that contributes to the appearance and progress of cancer and diabetes is the reversible phosphorylation of proteins, a process controlled by protein tyrosine-kinases (PTKs) and protein tyrosine-phosphatases (PTPs). Within the PTPs, PTP1B has gained significant interest since it is a validated target in drug discovery. Indeed, several PTP1B inhibitors have been developed, from both, synthesis and natural products. However, none have been approved by the FDA, due to their poor selectivity and/or pharmacokinetic properties. One of the most significant challenges to the discovery of PTP1B inhibitors (in vitro or in silico) is the use of truncated structures (PTP1B1-300), missing valuable information about the mechanisms of inhibition, and selectivity of ligands. The present study describes the biochemical characterization of a full-length PTP1B (hPTP1B1-400), as well as the description of phenalenones 1-4 and ursolic acid (5) as allosteric modulators. Compounds 1-5 showed inhibitory potential on hPTP1B1-400, with IC50 values ranging from 12.7 to 82.1 µM. Kinetic studies showed that 1 and 5 behave as mixed and non-competitive inhibitors, respectively. Circular dichroism experiments confirmed that 1 and 5 induced conformational changes to hPTP1B1-400. Further insights into the structure of hPTP1B1-400 were obtained from a homology model, which pointed out that the C-terminus (residues 301-400) is highly disordered. Molecular docking with the homologated model suggested that compounds 1 and 3-5 bind to the C-terminal domain, likely inducing conformational changes on the protein. Docking positions of compounds 1, 4, and 5 were refined with molecular dynamics simulations. Importantly, these simulations confirmed the high flexibility of the C-terminus of hPTP1B1-400, as well as the changes to its rigidity when bound to 1, 4, and 5.

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Preliminary analysis of the mass spectrometric (MS) and NMR spectroscopic data of the primary fractions from the biologically active extract of Salvia decora revealed spectra that are characteristic for neo-clerodane-type diterpenoids. MS-guided isolation of the bioactive fractions led to the isolation of three new chemical entities, including two hydroxy-neo-clerodanes (1 and 2) and one acylated 5,10-seco-neo-clerodane (3), along with three known diterpenoids (4-6), ursolic acid (7), and eupatorin (8). The structures of the new compounds were established by analysis of the 1D and 2D NMR and MS data, whereas their absolute configuration was deduced using a combination of experimental and theoretical ECD data and confirmed by X-ray crystallography (1 and 4). Furthermore, compounds 1, 3, 4, and 6-8 were evaluated as hPTP1B1-400 (human protein tyrosine phosphatase) inhibitors, where 7 showed the best activity, with an IC50 value in the lower µM range. Additionally, compound 7 was evaluated as an α-glucosidase inhibitor. The affinity constant of the 7-hPTP1B1-400 complex was determined by quenching fluorescence experiments (ka = 1.3 × 104 M-1), while the stoichiometry ratio (1:1 protein-ligand) was determined by a continuous variation method.

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RESUMEN Introducción: entre las enfermedades crónicas no transmisibles se encuentra el cáncer cérvico uterino, el cual constituye una de las principales causas de muerte en la actualidad. En los últimos años la morbilidad de este tipo de cáncer ha influido notablemente en los indicadores de salud y la calidad de vida de la población femenina mundial. Objetivo: diseñar una intervención educativa para la prevención del cáncer cérvico uterino, en estudiantes de primer año de la carrera de Medicina en la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: investigación de Desarrollo la cual requiere un estudio observacional, descriptivo, que se inserta en el Programa Ramal Enfermedades Crónicas no Transmisibles. El universo de estudio 740 adolescentes la muestra 246 alumnos, seleccionada mediante un muestreo sistemático. Resultados: la mayoría de los estudiantes reflejan como estado civil solteros o bajo unión consensual, el comienzo de las relaciones sexuales tiene mayor incidencia en las edades de 14 a 15 años aunque es significativa la cifra de adolescentes que entre los 16 y 17 años que inician las relaciones sexuales. En cuanto a la presencia de los factores de riesgo del cáncer cérvico uterino como múltiples compañeros sexuales, uso de tabletas anticonceptivas, presencia del hábito de fumar así como infecciones de transmisión sexual se evidenciaron con cifras más significativas múltiples compañeros sexuales y el uso de tabletas anticonceptivas, en cuanto a la distribución de motivos que impulsaron al inicio de las relaciones sexuales, se destacan los motivos de experimentar sensaciones nuevas, el hecho de complacer a la pareja y la presión grupal respectivamente, solo 5.28% responde a una búsqueda de placer. Conclusiones: los estudiantes presentan factores de riesgo de considerable magnitud de padecer cáncer cérvico uterino. Se diseñó la propuesta de intervención educativa.

ABSTRACT Introduction: cervical cancer is one of the non-communicable chronic diseases. It is currently one of the main causes of death. During the last years, this kind of cancer morbidity has notably struck on health and life quality indicators of female population around the world. Objective: to design an educative intervention for preventing cervical cancer in students of the first year of Medicine studies in the University of Medical Sciences of Matanzas. Materials and methods: development research demanding a descriptive, observational study, inserted in the Branch Program Non-communicable Chronic Diseases. The universe of study is 740 teenagers, and the sample, systematically sampled, 246 students. Results: most of students gave the category of single or consensual union as marital status; the beginning of sexual relationships has higher incidence at the age of 14-15 years, although it is significant the quantity of adolescents beginning sexual relationships at the ages of 16 and 17 years. In order to the presence of cervical cancer risk factors like multiple sexual partners, contraceptive tablets use, smoking habit and sexually transmitted infections (STI), multiple sexual partners and the use of contraceptive tablets showed the most significant quantities; and about the distribution of the motives boosting the beginning of sexual relationships are highlighted the motives of experimenting new sensations, the fact of pleasing the sexual partner and the group pressure, respectively; just 5.28 % answered it was looking for pleasure. Conclusions: students have considerable risk factors of suffering cervical cancer. A proposal of educative intervention was designed.

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Cuautepestalorin (4), a 7,8-dihydrochromene-oxoisochromane adduct bearing a spiro-polycyclic (6/6/6/6/6/6) ring system, along with its putative biosynthetic precursors, cytosporin M (1), cytosporin N (2), and oxopestalochromane (3), were isolated from the bioactive extract of Pestalotiopsis sp. using a combination of molecular networking and dereplication techniques. Their structures were elucidated using a set of spectroscopic, spectrometric, chiroptical (experimental and theoretical), and X-ray crystallography data. Compounds 3 and 4 exhibited modest potency when evaluated in vitro as α-glucosidase inhibitors.