An amplicon-based protocol for whole-genome sequencing of human respiratory syncytial virus subgroup A.

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.

Correlation of wastewater surveillance data with traditional influenza surveillance measures in Cook County, Illinois, October 2022-April 2023.

Influenza is a respiratory illness that can result in serious outcomes, particularly among persons who are immunocompromised, aged <5 years or aged >65 years. Traditional influenza surveillance approaches rely upon syndromic surveillance of emergency departments and public health reporting from clinicians and laboratories. Wastewater surveillance infrastructure developed to monitor SARS-CoV-2 is being used for influenza surveillance in the Chicago area. The goal was to evaluate timeliness and correlations between influenza virus detected through wastewater surveillance and traditional influenza surveillance measures to assess utility of wastewater surveillance for influenza at the county level. Specifically, we measured correlations between influenza virus gene copies in wastewater samples and 1) the number of intensive care unit admissions associated with a diagnosis of influenza, 2) the percentage emergency department (ED) visits for influenza-like-illness, and 3) the percentage of ED visits with influenza diagnosis at discharge2 in Cook County. Influenza concentrations in wastewater were strongly correlated with traditional influenza surveillance measures, particularly for catchment areas serving >100,000 residents. Wastewater indicators lagged traditional influenza surveillance measures by approximately one week when analyzed in cross-correlations. Although wastewater data lagged traditional influenza surveillance measures in this analysis, it can serve as a useful surveillance tool as a complement to syndromic surveillance; it is a form of influenza surveillance that does not rely on healthcare-seeking behavior or reporting by healthcare providers.

Harnessing the Reactivity of Duclauxin toward Obtaining hPTP1B1-400 Inhibitors.

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.

Embolización de un pseudoaneurisma de la arteria cística secundario a colecistitis aguda / Embolization of a pseudo aneurism of the cystic artery secondary to acute cholecystitis

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.

The Positive Effect of the Rational Addiction Prevention Program (RAPP) on Adolescents with High Risk for Drug Consumption.

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.

Mumps Cases Disproportionately Affecting Persons Living with HIV Infection and Men Who Have Sex with Men - Chicago, Illinois, 2018.

During January 1-March 2, 2018, the number of mumps cases among adults reported to the Chicago Department of Public Health (CDPH) doubled compared with the same period in 2017. In response, CDPH created a supplementary questionnaire to collect additional information on populations affected and potential transmission routes. An epidemiologic analysis of routine and supplementary data, including spatiotemporal analysis, was performed to describe mumps cases reported to CDPH during 2018. A fourfold increase in mumps cases was reported during 2018 compared with 2017, with men who have sex with men (MSM) and persons living with human immunodeficiency virus (HIV) infection disproportionately represented among cases. A spatiotemporal, residential cluster was identified in a 9-square-mile area within six adjacent communities. The majority of persons affected were MSM, and this area was visited by many other persons with mumps diagnoses. Spatiotemporal analyses could be used in real time to identify case clusters to target public health response efforts, including to guide recommendations for additional measles, mumps, and rubella (MMR) vaccine and to identify specific transmission venues.

Dimeric phenalenones from Talaromyces sp. (IQ-313) inhibit hPTP1B1-400: Insights into mechanistic kinetics from in vitro and in silico studies.

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.

Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora.

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.

Diseño de intervención educativa para la prevención del cáncer cérvico uterino en estudiantes universitarios / Design of educational intervention for the prevention of cervical cancer in university students

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 (AU).

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 (AU).

Diseño de intervención educativa para la prevención del cáncer cérvico uterino en estudiantes universitarios / Design of educational intervention for the prevention of cervical cancer in university students

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.

Cuautepestalorin, a 7,8-Dihydrochromene-Oxoisochromane Adduct Bearing a Hexacyclic Scaffold from Pestalotiopsis sp. IQ-011.

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.

Mentor-mentee interaction and laboratory social environment: Do they matter in doctoral students' publication productivity?

We explored the social shaping of science at the micro-level reality of face-to-face interaction in one of the traditional places for scientific activities-the scientific lab. We specifically examined how doctoral students' perception of their: (i) interaction with doctoral mentors (MMI) and (ii) lab social environment (LSE) influenced productivity. Construed as the production of peer-reviewed articles, we measured productivity using total number of articles (TOTAL), number of articles with impact factor greater than or equal to 4.00 (IFGE4), and number of first-authored articles (NFA). Via face-to-face interviews, we obtained data from n = 210 molecular biology Ph.D. students in selected universities in Japan, Singapore, and Taiwan. Additional productivity data (NFA) were obtained from online bibliometric databases. To summarize the original 13 MMI and 13 LSE semantic-differential items which we used to measure students' perceptions, principal component (PC) analyses were performed. The results were smaller sets of 4 MMI PCs and 4 LSE PCs. To identify which PCs influenced publication counts, we performed Poisson regression analyses. Although perceived MMI was not linked to productivity, perceived LSE was linked: Students who perceived their LSE as intellectually stimulating reported high levels of productivity in both TOTAL and IFGE4, but not in NFA. Our findings not only highlight how students' perception of their training environment factors in the production of scientific output, our findings also carry important implications for improving mentoring programs in science. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):130-144, 2017.

Pre-exposure to faeces or saliva of Triatoma dimidiata decreases parasitemia in mice challenged with Trypanosoma cruzi: a description of the inflammatory reaction at the inoculation site

Under natural conditions, Trypanosoma cruzi infection is transmitted to mammals when faeces contaminated with metacyclic trypomastigotes gain access through skin lesions, mucosa or bite wounds. Natural infection of bugs with T. cruzi can vary greatly from less than 1% up to 70%, depending on triatomine species: in the case of Triatoma dimidiata, the percentage of infection is around 30%. In this work uses biological fluids (saliva and faeces) from Triatoma dimidiata to inoculate experimental animals once or multiple times, before inoculation with faeces contaminated with metacyclic trypomastigotes discrete type unit Ia (TcI). The site of infection was analyzed for histological changes based on hematoxile-eosine technique and toluide blue stain for mast cells. Inoculation with saliva led to the recruitment of eosinophils and mononuclear cells at the inoculation site, whereas inoculation with faeces led to the recruitment of neutrophils. Mice inoculated multiple times exhibited a strong inflammatory reaction from the first hour. Mono- or multi-exposure to T. dimidiata fluids before inoculation with metacyclic trypomastigotes helped to control the level of parasitemia. Previous contact with saliva or faeces of T. dimidiata reduces parasitemia in T. cruzi I -infected mice.

Atom-at-a-time laser resonance ionization spectroscopy of nobelium.

Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements and theoretical modelling can be performed to high precision, taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown. These radioactive elements are produced in nuclear fusion reactions at rates of only a few atoms per second at most and must be studied immediately following their production, which has so far precluded their optical spectroscopy. Here we report laser resonance ionization spectroscopy of nobelium (No; atomic number 102) in single-atom-at-a-time quantities, in which we identify the ground-state transition 1S01P1. By combining this result with data from an observed Rydberg series, we obtain an upper limit for the ionization potential of nobelium. These accurate results from direct laser excitations of outer-shell electrons cannot be achieved using state-of-the-art relativistic many-body calculations that include quantum electrodynamic effects, owing to large uncertainties in the modelled transition energies of the complex systems under consideration. Our work opens the door to high-precision measurements of various atomic and nuclear properties of elements heavier than nobelium, and motivates future theoretical work.

Isotope dependence of the Zeeman effect in lithium-like calcium.

The magnetic moment µ of a bound electron, generally expressed by the g-factor µ=-g µB s h(-1) with µB the Bohr magneton and s the electron's spin, can be calculated by bound-state quantum electrodynamics (BS-QED) to very high precision. The recent ultra-precise experiment on hydrogen-like silicon determined this value to eleven significant digits, and thus allowed to rigorously probe the validity of BS-QED. Yet, the investigation of one of the most interesting contribution to the g-factor, the relativistic interaction between electron and nucleus, is limited by our knowledge of BS-QED effects. By comparing the g-factors of two isotopes, it is possible to cancel most of these contributions and sensitively probe nuclear effects. Here, we present calculations and experiments on the isotope dependence of the Zeeman effect in lithium-like calcium ions. The good agreement between the theoretical predicted recoil contribution and the high-precision g-factor measurements paves the way for a new generation of BS-QED tests.

Leveraging community concerns regarding meningococcal disease to address racial and socioeconomic disparities in immunization coverage.

Following the death of 2 adolescents due to serogroup C invasive meningococcal disease (SCIMD) in April 2008, the Chicago Department of Public Health (CDPH) observed a high level of concern in 2 Chicago communities inferred to have low meningococcal vaccine (MCV) coverage rates. In response, CDPH promptly mobilized additional resources, administering 5,343 doses of MCV in 40 schools over 2 weeks and immunizing 44% of enrolled students aged 11 to 18 years. The number of eligible students vaccinated per school ranged from 9 to 466 (median, 112) and the proportion of age-eligible students receiving the vaccine ranged from 5% to 87% (median, 52%). The attributes of the SCIMD activity did not meet the definition of a community-based outbreak, but presented an opportunity to promptly intensify existing mechanisms for meningococcal vaccination of adolescents in the affected neighborhoods and overcome traditional barriers to vaccination.