Optimization of a translational murine model of closed-head traumatic brain injury.

Traumatic brain injury (TBI) from closed-head trauma is a leading cause of disability, with limited effective interventions. Many TBI models impact brain parenchyma directly, and are limited by the fact that these forces do not recapitulate clinically relevant closed head injury. However, applying clinically relevant injury mechanics to the intact skull may lead to variability and as a result, preclinical modeling TBI remains a challenge. Current models often do not explore sex differences in TBI, which is critically important for translation to clinical practice. We systematically investigated sources of variability in a murine model of closed-head TBI and developed a framework to reduce variability across severity and sex. We manipulated pressure, dwell time, and displacement to determine effects on motor coordination, spatial learning, and neuronal damage in 10-week-old male and female mice. Increasing pressure beyond 70 psi had a ceiling effect on cellular and behavioral outcomes, while manipulating dwell time only affected behavioral performance. Increasing displacement precisely graded injury severity in both sexes across all outcomes. Physical signs of trauma occurred more frequently at higher displacements. Stratifying severity based on day-1 rotarod performance retained histological relationships and separated both sexes into injury severity cohorts with distinct patterns of behavioral recovery. Utilizing this stratification strategy, within-group rotarod variability over 6 days post-injury was reduced by 50%. These results have important implications for translational research in TBI and provide a framework for using this clinically relevant translational injury model in both male and female mice.

Associations of current and childhood socioeconomic status and health outcomes amongst patients with knee or hip osteoarthritis in a Mexico City family-practice setting.

OBJECTIVES: To examine the association of current and childhood socioeconomic status (SES) with patient-reported functional status, quality of life and disability in patients with knee or hip osteoarthritis (OA). METHODS: Cross-sectional study amongst individuals seeking care for any medical reason in a primary care family-practice clinic in Mexico City. We included individuals with self-reported doctor-diagnosed arthritis, recruited through waiting-room posters and invitations by treating family physicians. We administered a survey using validated Spanish language versions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Osteoarthritis of Lower Limbs and Quality of Life (AMICAL), and the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI). To estimate current and childhood SES, we collected data on education level and occupation type for both the patient and their parents, as well as using a validated tool to estimate income quintile. RESULTS: We recruited 154 patients and excluded 8 patients. There was a high correlation between outcome scores. Estimated income and education levels were correlated with WOMAC, AMICAL and HAQ-DI scores, and significant differences were found in all scores by occupation type. The associations for current SES variables and outcome scores remained significant independently of age, sex, BMI, and presence of diabetes or hypertension, and were largely explained by current income in mutually adjusted models. Childhood SES - in particular as measured through maternal education - was best correlated with AMICAL scores, though its effect seemed largely mediated by its association with current SES. CONCLUSIONS: Current Socioeconomic Status impacts functional status, quality of life and disability amongst OA patients in Mexico City. The WOMAC, AMICAL and HAQ-DI scores correlate with each other and are all potentially useful markers of disease severity. More research is needed to elucidate the relationships between childhood SES and OA outcomes. Awareness of life-course SES may be useful in identifying patients at risk for worse outcomes.

Streptococcus pneumoniae serotype 19A in hospitalized children with invasive pneumococcal disease after the introduction of conjugated vaccines in Lima, Peru.

BACKGROUND: The Pneumococcal conjugate vaccine (PCV) has decreased cases of invasive pneumococcal disease (IPD) worldwide. However, the impact of PCVs introduction may be affected by the serotype distribution in a specific context. METHODS: Cross-sectional multicenter passive surveillance study of IPD cases in pediatric patients hospitalized in Lima, Peru between 2016 and 2019 (after PCV13 introduction) to determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. Serotyping was performed by a sequential multiplex PCR and confirmed by whole genome sequencing. RESULTS: Eighty-five S. pneumoniae isolates were recovered (4.07/100,000 among children <60 months of age). Serotype 19A was the most common (49.4%). Children infected with serotype 19A in comparison with children infected with other serotypes were younger, had a lower rate of meningitis and higher rates of pneumonia, complicated pneumonia and antimicrobial resistance; 28.6% of patients with serotype 19A have received at least one dose of PCV13 vs. 62.8% of patients with other serotypes. Using MIC-breakpoints, 81.2% (56/69) of non-meningitis strains and 31.2% (5/16) of meningitis strains were susceptible to penicillin; 18.8% (3/16) of meningitis strains had intermediate resistance to ceftriaxone. Resistance to azithromycin was 78.8% (67/85). Serotype 19A frequency increased over time in the same study population, from 4.2% (4/96) in 2006-2008, to 8.6% (5/58) in 2009-2011, to 49.4% (42/85) in the current study (2016-2019) (p < 0.001). CONCLUSIONS: After PCV13 introduction in Peru, serotype 19A remains the most prevalent; however, the vaccination coverage is still not optimal. Therefore, additonal surveillance studies are needed to determine the remaining IPD burden.

[Factors associated with benzodiazepines dependence in insomnia patients]. / Factores asociados a la dependencia a benzodiacepinas en pacientes con insomnio.

Background: The use of benzodiazepines as a treatment for insomnia can have side effects such as impaired coordination causing falls in adults and even dependence. Objective: To assess the factors associated with dependence on benzodiazepines in patients with insomnia. Methods: Observational, cross-sectional, prospective, and analytical study, at the first level of care. Patients older than 18 years with a diagnosis of insomnia and a benzodiazepine prescription were selected. The dependency was measured with the International Neuropsychiatric Interview. Results: 107 patients were included. Median age 67 years, predominantly female (72%), 74% attended secondary school or more, 71% had more than 3 years of diagnosis, 84% used clonazepam. The 54% presented dependency. In the bivariate analysis, schooling RM 0.392 (95%CI: 0.15-0.96) p = 0.038, moderate and severe clinical insomnia RM 3.618 (95%CI: 1.44-9.08) p = 0.005 and more than 3 years of diagnosis RM 2.428 (95%CI: 1.03-5.71) p = 0.040. In the multivariate model, schooling (p = 0.084), years of diagnosis (p = 0.062) and frequency of consumption (p = 0.065) obtained an R2 of 0.13. Conclusions: Primary schooling showed a lower risk of presenting dependence on benzodiazepines. The risk was increased in those with more than 3 years of diagnosis, and in those with moderate and severe insomnia.

Introducción: el uso de benzodiacepinas como tratamiento para el insomnio puede tener efectos secundarios, como el deterioro de la coordinación que puede provocar caídas en adultos e, incluso, dependencia. Objetivo: evaluar los factores asociados a la dependencia a benzodiacepinas en pacientes con insomnio. Material y métodos: estudio observacional, transversal, prospectivo y analítico, llevado a cabo en el primer nivel de atención. Se seleccionaron pacientes mayores de 18 años con diagnóstico de insomnio y prescripción de benzodiacepina. La dependencia se midió con la Entrevista Neuropsiquiátrica Internacional. Resultados: se incluyeron 107 pacientes, la mediana de edad fue de 67 años, con predominio del sexo femenino (72%), el 74% cursó educación secundaria o más, el 71% tenía más de tres años con diagnóstico de insomnio, el 84% usaba clonazepan. El 54% presentó dependencia. En el análisis bivariado, la escolaridad primaria mostró una razón de momios (RM) de 0.392 (IC95%: 0.15-0.96), p = 0.038; el insomnio clínico moderado y grave RM de 3.618 (IC95%: 1.44-9.08) p = 0.005, y más de tres años de diagnóstico con una RM de 2.428 (IC95%: 1.03-5.71) p = 0.040. En el modelo multivariado, la escolaridad (p = 0.084), los años de diagnóstico (p = 0.062) y la frecuencia de consumo (p = 0.065) obtuvieron una R2 de 0.13. Conclusiones: los pacientes con escolaridad primaria mostraron un menor riesgo de presentar dependencia a benzodiacepinas. El riesgo se incrementó en los pacientes con más de tres años de diagnóstico y en aquellos con insomnio moderado y grave.

Pneumococcal serotypes and antibiotic resistance in healthy carriage children after introduction of PCV13 in Lima, Peru.

OBJECTIVE: To determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7). METHODS: A cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes. RESULTS: The pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001). CONCLUSION: The introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.

Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.

The underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box-binding protein-1 (Xbp1s), a key effector of UPR signaling, in forebrain excitatory neurons, rapidly develop neurologic deficits, most notably recurrent spontaneous seizures. This seizure phenotype begins around 8 days after Xbp1s transgene expression is induced in XBP1s-TG mice, and by approximately 14 days post induction, the seizures evolve into status epilepticus with nearly continuous seizure activity followed by sudden death. Animal death is likely due to severe seizures because the anticonvulsant valproic acid could significantly prolong the lives of XBP1s-TG mice. Mechanistically, our gene profiling analysis indicates that compared to control mice, XBP1s-TG mice exhibit 591 differentially regulated genes (mostly upregulated) in the brain, including several GABAA receptor genes that are notably downregulated. Finally, whole-cell patch clamp analysis reveals a significant reduction in both spontaneous and tonic GABAergic inhibitory responses in Xbp1s-expressing neurons. Taken together, our findings unravel a link between XBP1s signaling and seizure occurrence.

Recommendations for modernizing infant vaccination schedules with combination vaccines in Colombia and Peru.

The objective of this article was to consider the vaccination challenges in Colombia and Peru and the role of pediatric combination vaccines in overcoming these challenges. Barriers to including new vaccines with more antigens remain apparent in parts of these countries, where vaccine-preventable diseases in infants continue to be a major problem. The challenges include the heterogeneity of vaccine coverage within each country and in neighboring countries, which can contribute to poor rates of vaccination coverage; the adverse impact of the inward migration of unvaccinated individuals, which has favored the re-emergence of vaccine-preventable diseases; vaccine shortages; and the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the associated shifts in health care resources. To improve the coverage of pediatric vaccines in Colombia and Peru, it will be necessary to ensure the widespread integration into vaccine schedules of combination vaccines containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b and hepatitis B antigens with a three-dose primary series delivered at 2, 4 and 6 months of age followed by a booster at 18 months of age. Such vaccines play important roles in preventing diphtheria, tetanus and pertussis; eradicating polio; and providing boosting against H. influenzae type b.

El objetivo de este artículo es considerar los desafíos que se enfrentan en Colombia y Perú con respecto a la vacunación y el papel de las vacunas combinadas pediátricas para superar estos desafíos. Los obstáculos para incluir vacunas nuevas con más antígenos siguen siendo evidentes en algunos lugares de estos países, donde las enfermedades prevenibles por vacunación en menores de 1 año continúan siendo un grave problema. Entre los desafíos se incluye la heterogeneidad de la cobertura de vacunación en cada país y en los países vecinos, lo que puede contribuir con que se registren tasas bajas de cobertura de vacunación; el impacto adverso de la migración interna de personas no vacunadas, lo que ha favorecido la reaparición de enfermedades prevenibles por vacunación; la escasez de vacunas, y el impacto de la pandemia del coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) y los consiguientes cambios en los recursos de atención médica. Para mejorar la cobertura de las vacunas pediátricas en Colombia y Perú será necesario integrar de manera generalizada en los calendarios de vacunación vacunas combinadas con antígenos de difteria, tétanos, tos ferina acelular, poliovirus inactivados, Haemophilus influenzae tipo b y hepatitis B con una serie primaria de tres dosis administradas a los 2, 4 y 6 meses de edad, seguida de un refuerzo a los 18 meses de edad. Esas vacunas desempeñan un papel esencial en la prevención de la difteria, el tétanos y la tos ferina; la erradicación de la polio; y el refuerzo contra H. influenzae tipo b.

O objetivo deste artigo foi avaliar os desafios da vacinação na Colômbia e no Peru e o papel das vacinas pediátricas combinadas na superação de tais desafios. Os obstáculos para incluir novas vacinas com mais antígenos permanecem visíveis em partes desses países, onde doenças imunopreveníveis em lactentes continuam a ser um grande problema. Os desafios incluem a heterogeneidade da cobertura vacinal dentro de cada país e nos países vizinhos, o que pode contribuir para baixas taxas de cobertura vacinal; o impacto adverso da migração interna de pessoas não vacinadas, o que favoreceu o ressurgimento de doenças imunopreveníveis; a escassez de vacinas; e o impacto da pandemia de síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) e mudanças relacionadas nos recursos de atenção à saúde. Para melhorar a cobertura das vacinas pediátricas na Colômbia e no Peru, será necessário assegurar sua integração generalizada em esquemas de vacinas combinadas contendo antígenos de difteria, tétano, pertussis acelular, poliovírus inativado, Haemophilus influenzae tipo B e hepatite B, com uma série primária de três doses aplicadas aos 2, 4 e 6 meses de idade seguidas de um reforço aos 18 meses de idade. Tais vacinas desempenham papéis importantes na prevenção da difteria, tétano e coqueluche; na erradicação da poliomielite; e no reforço contra H. influenzae tipo b.

Recommendations for modernizing infant vaccination schedules with combination vaccines in Colombia and Peru

[ABSTRACT]. The objective of this article was to consider the vaccination challenges in Colombia and Peru and the role of pediatric combination vaccines in overcoming these challenges. Barriers to including new vaccines with more antigens remain apparent in parts of these countries, where vaccine-preventable diseases in infants continue to be a major problem. The challenges include the heterogeneity of vaccine coverage within each country and in neighboring countries, which can contribute to poor rates of vaccination coverage; the adverse impact of the inward migration of unvaccinated individuals, which has favored the re-emergence of vaccine-preventable diseases; vaccine shortages; and the impact of the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) pandemic and the associated shifts in health care resources. To improve the coverage of pediatric vaccines in Colombia and Peru, it will be necessary to ensure the widespread integration into vaccine sched- ules of combination vaccines containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b and hepatitis B antigens with a three-dose primary series delivered at 2, 4 and 6 months of age followed by a booster at 18 months of age. Such vaccines play important roles in preventing diphtheria, tetanus and pertussis; eradicating polio; and providing boosting against H. influenzae type b.

[RESUMEN]. El objetivo de este artículo es considerar los desafíos que se enfrentan en Colombia y Perú con respecto a la vacunación y el papel de las vacunas combinadas pediátricas para superar estos desafíos. Los obstáculos para incluir vacunas nuevas con más antígenos siguen siendo evidentes en algunos lugares de estos países, donde las enfermedades prevenibles por vacunación en menores de 1 año continúan siendo un grave pro- blema. Entre los desafíos se incluye la heterogeneidad de la cobertura de vacunación en cada país y en los países vecinos, lo que puede contribuir con que se registren tasas bajas de cobertura de vacunación; el impacto adverso de la migración interna de personas no vacunadas, lo que ha favorecido la reaparición de enfermedades prevenibles por vacunación; la escasez de vacunas, y el impacto de la pandemia del corona- virus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) y los consiguientes cambios en los recursos de atención médica. Para mejorar la cobertura de las vacunas pediátricas en Colombia y Perú será necesario integrar de manera generalizada en los calendarios de vacunación vacunas combinadas con antígenos de difteria, tétanos, tos ferina acelular, poliovirus inactivados, Haemophilus influenzae tipo b y hepatitis B con una serie primaria de tres dosis administradas a los 2, 4 y 6 meses de edad, seguida de un refuerzo a los 18 meses de edad. Esas vacunas desempeñan un papel esencial en la prevención de la difteria, el tétanos y la tos ferina; la erradicación de la polio; y el refuerzo contra H. influenzae tipo b.

[RESUMO]. O objetivo deste artigo foi avaliar os desafios da vacinação na Colômbia e no Peru e o papel das vacinas pediátricas combinadas na superação de tais desafios. Os obstáculos para incluir novas vacinas com mais antígenos permanecem visíveis em partes desses países, onde doenças imunopreveníveis em lactentes con- tinuam a ser um grande problema. Os desafios incluem a heterogeneidade da cobertura vacinal dentro de cada país e nos países vizinhos, o que pode contribuir para baixas taxas de cobertura vacinal; o impacto adverso da migração interna de pessoas não vacinadas, o que favoreceu o ressurgimento de doenças imu- nopreveníveis; a escassez de vacinas; e o impacto da pandemia de síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) e mudanças relacionadas nos recursos de atenção à saúde. Para melhorar a cobertura das vacinas pediátricas na Colômbia e no Peru, será necessário assegurar sua integração gen- eralizada em esquemas de vacinas combinadas contendo antígenos de difteria, tétano, pertussis acelular, poliovírus inativado, Haemophilus influenzae tipo B e hepatite B, com uma série primária de três doses aplica- das aos 2, 4 e 6 meses de idade seguidas de um reforço aos 18 meses de idade. Tais vacinas desempenham papéis importantes na prevenção da difteria, tétano e coqueluche; na erradicação da poliomielite; e no reforço contra H. influenzae tipo b.

Recommendations for modernizing infant vaccination schedules with combination vaccines in Colombia and Peru / Recomendaciones para modernizar los calendarios de vacunación infantil con vacunas combinadas en Colombia y Perú / Recomendações para modernizar os esquemas de vacinação infantil com vacinas combinadas na Colômbia e no Peru

ABSTRACT The objective of this article was to consider the vaccination challenges in Colombia and Peru and the role of pediatric combination vaccines in overcoming these challenges. Barriers to including new vaccines with more antigens remain apparent in parts of these countries, where vaccine-preventable diseases in infants continue to be a major problem. The challenges include the heterogeneity of vaccine coverage within each country and in neighboring countries, which can contribute to poor rates of vaccination coverage; the adverse impact of the inward migration of unvaccinated individuals, which has favored the re-emergence of vaccine-preventable diseases; vaccine shortages; and the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the associated shifts in health care resources. To improve the coverage of pediatric vaccines in Colombia and Peru, it will be necessary to ensure the widespread integration into vaccine schedules of combination vaccines containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b and hepatitis B antigens with a three-dose primary series delivered at 2, 4 and 6 months of age followed by a booster at 18 months of age. Such vaccines play important roles in preventing diphtheria, tetanus and pertussis; eradicating polio; and providing boosting against H. influenzae type b.

RESUMEN El objetivo de este artículo es considerar los desafíos que se enfrentan en Colombia y Perú con respecto a la vacunación y el papel de las vacunas combinadas pediátricas para superar estos desafíos. Los obstáculos para incluir vacunas nuevas con más antígenos siguen siendo evidentes en algunos lugares de estos países, donde las enfermedades prevenibles por vacunación en menores de 1 año continúan siendo un grave problema. Entre los desafíos se incluye la heterogeneidad de la cobertura de vacunación en cada país y en los países vecinos, lo que puede contribuir con que se registren tasas bajas de cobertura de vacunación; el impacto adverso de la migración interna de personas no vacunadas, lo que ha favorecido la reaparición de enfermedades prevenibles por vacunación; la escasez de vacunas, y el impacto de la pandemia del coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) y los consiguientes cambios en los recursos de atención médica. Para mejorar la cobertura de las vacunas pediátricas en Colombia y Perú será necesario integrar de manera generalizada en los calendarios de vacunación vacunas combinadas con antígenos de difteria, tétanos, tos ferina acelular, poliovirus inactivados, Haemophilus influenzae tipo b y hepatitis B con una serie primaria de tres dosis administradas a los 2, 4 y 6 meses de edad, seguida de un refuerzo a los 18 meses de edad. Esas vacunas desempeñan un papel esencial en la prevención de la difteria, el tétanos y la tos ferina; la erradicación de la polio; y el refuerzo contra H. influenzae tipo b.

RESUMO O objetivo deste artigo foi avaliar os desafios da vacinação na Colômbia e no Peru e o papel das vacinas pediátricas combinadas na superação de tais desafios. Os obstáculos para incluir novas vacinas com mais antígenos permanecem visíveis em partes desses países, onde doenças imunopreveníveis em lactentes continuam a ser um grande problema. Os desafios incluem a heterogeneidade da cobertura vacinal dentro de cada país e nos países vizinhos, o que pode contribuir para baixas taxas de cobertura vacinal; o impacto adverso da migração interna de pessoas não vacinadas, o que favoreceu o ressurgimento de doenças imunopreveníveis; a escassez de vacinas; e o impacto da pandemia de síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) e mudanças relacionadas nos recursos de atenção à saúde. Para melhorar a cobertura das vacinas pediátricas na Colômbia e no Peru, será necessário assegurar sua integração generalizada em esquemas de vacinas combinadas contendo antígenos de difteria, tétano, pertussis acelular, poliovírus inativado, Haemophilus influenzae tipo B e hepatite B, com uma série primária de três doses aplicadas aos 2, 4 e 6 meses de idade seguidas de um reforço aos 18 meses de idade. Tais vacinas desempenham papéis importantes na prevenção da difteria, tétano e coqueluche; na erradicação da poliomielite; e no reforço contra H. influenzae tipo b.

Time-varying caloric vestibular stimulation for the treatment of neurodegenerative disease.

Time-varying caloric vestibular stimulation (tvCVS) is a new form of non-invasive neuromodulation similar to, but different from, diagnostic caloric vestibular stimulation (CVS). Using a non-invasive, solid-state delivery device, tvCVS has been successfully used in a human clinical trial with Parkinson's disease (PD) subjects. Additionally, the effects of tvCVS on brain activation have been studied in healthy human subjects using transcranial Doppler sonography (TCD) and functional magnetic resonance imaging (BOLD fMRI). A novel finding in the TCD and fMRI studies was the induction of cerebral blood flow velocity (CBFv) oscillations. How such oscillations might lead to the observed clinical effects seen in PD subjects will be discussed. Enabling studies of tvCVS with rodents is an attractive goal in support of explorations of the mechanism of action. Male Wistar rats were used in a proof-of-concept study described herein. Rats were anesthetized (isoflurane) and ventilated for the duration of the tvCVS runs. Time-varying thermal stimuli were administered using a digital temperature controller to modulate Peltier-type heater/cooler devices. Blunt ear bars conveyed the thermal stimulus to the external ear canals of the rats. Different thermal waveform combinations were evaluated for evidence of successful induction of the CVS effect. It was found that bilateral triangular thermal waveforms could induce oscillations in CBFv both during and after the application of tvCVS. These oscillations were similar to, but different from those observed in awake human subjects. The establishment of a viable animal model for the study of tvCVS will augment ongoing clinical investigations of this new form of neuromodulation in patients with neurodegenerative disease.

[Impact of the COVID-19 pandemic on the performance and academic experience of undergraduate interns]. / Impacto del COVID-19 en el desempeño y experiencia académica de médicos internos.

Background: The COVID-19 pandemic has had a great impact and high cost on the education of physicians that has not been determined in the long term. Objective: To determine the impact of COVID-19 on undergraduate interns and how it affected their academic training. Material and methods: Mixed study. Qualifications of the bimonthly departmental exam from 2018 to 2020 of the FACMED-UNAM internal doctors were reviewed, the focus group technique was used to investigate their experience and repercussions during the pandemic. Results: The grade point average for 18-19 was 70.76+/- 10.12. In 2020 76.19+/-10.66 (p = 0.000). In the CDMX 2018-2019 an average 70,405+/-10,156 against 71.97+/- 10.28 of foreign headquarters (p > 0.05). In 2020, the capital's headquarters an average of 77.02+/-10.31 against 73.86+/-11.296 in the interior (p = 0.000). When comparing the bimonthly ratings, there were no significant differences in 2018 and 2019; However, in 2020 there is an increase from 69.40 +/-9.538 to 79.39 +/-10.709. Conclusions: The ratings for 2020 had better results in relation to 2018 and 2019, they were higher in capital cities in relation to foreign ones. The retrospective perception of the inmates was that they had more time to study thematic contents and less pressure in the care work; They stated that they would have preferred to stay in their rotations, with the necessary protective equipment to avoid getting infected.

Introducción: la pandemia por COVID-19 ha tenido un gran impacto y alto costo en la educación de los médicos en formación que no ha sido determinado a largo plazo. Objetivo: determinar el impacto del COVID-19 en médicos internos de pregrado y cómo repercutió en su formación académica. Material y métodos: estudio mixto en el que se revisaron las calificaciones del examen departamental bimestral del 2018 al 2020 de los médicos internos Facultad de Medicina de la Universidad Nacional Autónoma de México; se utilizó la técnica de grupos focales para indagar su experiencia y repercusiones durante la pandemia. Resultados: el promedio de calificaciones de los años 2018-2019 fue de 70.76 +/- 10.12. En el 2020 de 76.19 +/- 10.66 (p = 0.000). En la CDMX durante 2018-2019 se registró una media de 70.40 +/- 10.15 frente a 71.97 +/- 10.28 de las sedes foráneas (p > 0.05). En el 2020, las sedes de la capital tuvieron una media de 77.02 +/- 10.31 frente a 73.86 +/- 11.296 de las del interior (p = 0.000). Al comparar las calificaciones bimestrales, no hubo diferencias significativas en 2018 y 2019; sin embargo, en el 2020 hubo una elevación de 69.40 +/- 9.538 a 79.39 +/- 10.70. Conclusiones: se registraron mejores resultados en las calificaciones del 2020 en relación con las del 2018 y 2019, estas fueron más altas en las sedes capitalinas en relación con las foráneas. La percepción retrospectiva de los internos fue que dispusieron de más tiempo para el estudio de contenidos temáticos y menor presión en el trabajo asistencial; declararon que hubieran preferido quedarse en sus rotaciones, con el equipo de protección necesario para evitar contagiarse.

Increase of Macrolide-Resistance in Streptococcus pneumoniae Strains After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Lima, Peru.

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.

Impacto del COVID-19 en el desempeño y experiencia académica de médicos internos / Impact of the COVID-19 pandemic on the performance and academic experience of undergraduate interns

Introducción: la pandemia por COVID-19 ha tenido un gran impacto y alto costo en la educación de los médicos en formación que no ha sido determinado a largo plazo. Objetivo: determinar el impacto del COVID-19 en médicos internos de pregrado y cómo repercutió en su formación académica. Material y métodos: estudio mixto en el que se revisaron las calificaciones del examen departamental bimestral del 2018 al 2020 de los médicos internos Facultad de Medicina de la Universidad Nacional Autónoma de México; se utilizó la técnica de grupos focales para indagar su experiencia y repercusiones durante la pandemia. Resultados: el promedio de calificaciones de los años 2018-2019 fue de 70.76 +/- 10.12. En el 2020 de 76.19 +/- 10.66 (p = 0.000). En la CDMX durante 2018-2019 se registró una media de 70.40 +/- 10.15 frente a 71.97 +/- 10.28 de las sedes foráneas (p > 0.05). En el 2020, las sedes de la capital tuvieron una media de 77.02 +/- 10.31 frente a 73.86 +/- 11.296 de las del interior (p = 0.000). Al comparar las calificaciones bimestrales, no hubo diferencias significativas en 2018 y 2019; sin embargo, en el 2020 hubo una elevación de 69.40 +/- 9.538 a 79.39 +/- 10.70. Conclusiones: se registraron mejores resultados en las calificaciones del 2020 en relación con las del 2018 y 2019, estas fueron más altas en las sedes capitalinas en relación con las foráneas. La percepción retrospectiva de los internos fue que dispusieron de más tiempo para el estudio de contenidos temáticos y menor presión en el trabajo asistencial; declararon que hubieran preferido quedarse en sus rotaciones, con el equipo de protección necesario para evitar contagiarse.

Background: The COVID-19 pandemic has had a great impact and hig+h cost on the education of physicians that has not been determined in the long term. Objective: To determine the impact of COVID-19 on undergraduate interns and how it affected their academic training. Material and methods: Mixed study. Qualifications of the bimonthly departmental exam from 2018 to 2020 of the FACMED-UNAM internal doctors were reviewed, the focus group technique was used to investigate their experience and repercussions during the pandemic. Results: The grade point average for 18-19 was 70.76+/10.12. In 2020 76.19+/-10.66 (p = 0.000). In the CDMX 2018-2019 an average 70,405+/-10,156 against 71.97+/10.28 of foreign headquarters (p > 0.05). In 2020, the capital's headquarters an average of 77.02+/-10.31 against 73.86+/-11.296 in the interior (p = 0.000). When comparing the bimonthly ratings, there were no significant differences in 2018 and 2019; However, in 2020 there is an increase from 69.40 +/-9.538 to 79.39 +/-10.709. Conclusions: The ratings for 2020 had better results in relation to 2018 and 2019, they were higher in capital cities in relation to foreign ones. The retrospective perception of the inmates was that they had more time to study thematic contents and less pressure in the care work; They stated that they would have preferred to stay in their rotations, with the necessary protective equipment to avoid getting infected.

Endovascular middle cerebral artery embolic stroke model: a novel approach.

A video (video 1) describing a novel murine endovascular embolic stroke model is presented. Traditional middle cerebral artery (MCA) occlusion models include a blind insertion of a monofilament string1 2 into the common or external carotid artery with the expectation to selectively occlude the MCA. However, significant mortality occurs due to subarachnoid hemorrhage and variability in stroke size, possibly related to the filament's malposition-for example, external carotid or proximal internal carotid artery (ICA). Additionally, while the string is in place, it occludes the entire extracranial ICA affecting also the collateral pial circulation. neurintsurg;14/4/413/V1F1V1Video 1 Our model includes tail artery access, which tolerates several procedures facilitating survival studies. This model uses autologous blood3 4 clot deployed directly into the MCA, resembling what occurs in clinical practice. Autologous thrombi could be lysed with IA/IV tissue plasminogen activator.In summary, we describe a novel model that resembles real practice, permits multiple catheterizations, results in reliable embolization under fluoroscopic guidance and allows therapeutic interventions not available with traditional models.

Effects of Temperature on Enantiomerization Energy and Distribution of Isomers in the Chiral Cu13 Cluster.

In this study, we report the lowest energy structure of bare Cu13 nanoclusters as a pair of enantiomers at room temperature. Moreover, we compute the enantiomerization energy for the interconversion from minus to plus structures in the chiral putative global minimum for temperatures ranging from 20 to 1300 K. Additionally, employing nanothermodynamics, we compute the probabilities of occurrence for each particular isomer as a function of temperature. To achieve that, we explore the free energy surface of the Cu13 cluster, employing a genetic algorithm coupled with density functional theory. Moreover, we discuss the energetic ordering of isomers computed with various density functionals. Based on the computed thermal population, our results show that the chiral putative global minimum strongly dominates at room temperature.

Theoretical Prediction of Structures, Vibrational Circular Dichroism, and Infrared Spectra of Chiral Be4B8 Cluster at Different Temperatures.

Lowest-energy structures, the distribution of isomers, and their molecular properties depend significantly on geometry and temperature. Total energy computations using DFT methodology are typically carried out at a temperature of zero K; thereby, entropic contributions to the total energy are neglected, even though functional materials work at finite temperatures. In the present study, the probability of the occurrence of one particular Be4B8 isomer at temperature T is estimated by employing Gibbs free energy computed within the framework of quantum statistical mechanics and nanothermodynamics. To identify a list of all possible low-energy chiral and achiral structures, an exhaustive and efficient exploration of the potential/free energy surfaces is carried out using a multi-level multistep global genetic algorithm search coupled with DFT. In addition, we discuss the energetic ordering of structures computed at the DFT level against single-point energy calculations at the CCSD(T) level of theory. The total VCD/IR spectra as a function of temperature are computed using each isomer's probability of occurrence in a Boltzmann-weighted superposition of each isomer's spectrum. Additionally, we present chemical bonding analysis using the adaptive natural density partitioning method in the chiral putative global minimum. The transition state structures and the enantiomer-enantiomer and enantiomer-achiral activation energies as a function of temperature evidence that a change from an endergonic to an exergonic type of reaction occurs at a temperature of 739 K.

Impact of arsenic exposure on clinicopathological characteristics of bladder cancer: A comparative study between patients from an arsenic-exposed region and nonexposed reference sites.

BACKGROUND: Beyond exposure to arsenic in drinking-water, there is few information about demographic and clinicopathological features of patients with bladder cancer living in arsenic-exposed regions. The aim of the study was to assess the impact of arsenic exposure on clinicopathological characteristics in patients with bladder cancer from a contaminated region compared to those of 2 reference areas. METHODS: Data of 285 patients with bladder cancer (83 with arsenic exposure from Antofagasta and 202 controls from 2 different sites in Santiago) were obtained through personal interviews and from review of medical records. Demographic, clinicopathological parameters, and information on relevant environmental risk factors were compared with parametric and nonparametric tests as needed. Multivariable analysis was performed to identify independent predictors for high grade and muscle-invasive disease (T2-4). RESULTS: We found no significant differences between groups regarding age at presentation (66.4 vs. 66.5 and 67.2 years; P = 0.69, for exposed vs. the 2 nonexposed groups, respectively) and female gender (28.9% vs. 29.8% and 26.2%; P = 0.84). Proportion of current smokers was significantly lower in the exposed population (10.7% vs. 38.6% and 26.9%; P < 0.001). There was a significantly higher proportion of locally advanced (10.8 vs. 1.8 and 0.7% T3/4; P = 0.002) and high-grade tumors (79.5% vs. 63.2% and 64.1%; P = 0.001) within arsenic-exposed patients. Arsenic exposure was the only significant predictor for the presence of high-grade tumors (adjusted OR: 5.10; 95%CI: 2.03-12.77) on multivariable analysis. CONCLUSIONS: Our study revealed relevant clinical differences in bladder cancer patients with a history of arsenic exposure as compared to nonexposed cases. The more aggressive phenotype associated to arsenic-related bladder cancer should be considered when designing efficient screening strategies for this high-risk population.

Annular pancreas, cause of abdominal pain: Case report / Páncreas anular, causa de dolor abdominal. Reporte de caso

Background: Annular pancreas is a congenital abnormality which causes duodenal obstruction in neonates. It befalls upon 1 patient amongst every 12 000-15 000 newborns. It often appears in adulthood. Clinical traits include abdominal pain, intestinal obstruction, vomiting, and pancreatitis. The diagnosis requires image studies and surgical exploration. Clinical case: Female patient, 11 years of age, presenting intermittent chronic abdominal pain, underweight for her age. Treated by a private physician with ranitidine (4 mg/kg/day) and ibuprofen (5 mg/kg/dose) orally, for one month, due to acid-peptic disease. On December 31, 2017, she was attended at Pediatric Emergency presenting epigastric pain, and nausea. She vomited bile contents 4 times over a 24 hour span. Other symptoms included painful reaction to epigastric palpation, positive pancreatic points, negative Murphy's sign, no hepatomegaly or splenomegaly, decreased peristaltic noises. Reported: amylase 2163 U/L, lipase 821 U/L, lactic dehydrogenase 461 U/L. Pancreatic ultrasound: 19.3 mm head, 23.2 mm body and 10 mm tail. She was admitted to pediatrics, where the annular pancreas condition was confirmed through ultrasound and computed tomography scan. She then underwent conservative treatment. Conclusion: The patient displayed typical annular pancreas symptoms. Image studies were key to the diagnosis.

Introducción: el páncreas anular es una anomalía congénita que causa obstrucción duodenal en el neonato. Se reporta en 1 por cada 12 000-15 000 recién nacidos, a menudo se revela en la edad adulta. Clínicamente incluye obstrucción intestinal, dolor abdominal, vómitos y puntos pancreáticos positivos. El diagnóstico requiere estudios de imagenología y exploración quirúrgica. Caso clínico: paciente del sexo femenino, de 11 años de edad, con dolor abdominal crónico intermitente, de bajo peso para su edad. Tratada por médico privado con ranitidina (4 mg/kg/día) e ibuprofeno (5 mg/kg/dosis) vía oral, durante un mes, por enfermedad acido-péptica. El 31 de diciembre del 2017 fue atendida en urgencias pediátricas, por dolor en epigastrio, náuseas y vómitos de contenido gastrobiliar en número de 4 en 24 horas. Abdomen doloroso a la palpación en epigastrio, puntos pancreáticos positivos, Murphy negativo, sin hepatomegalia ni esplenomegalia, ruidos peristálticos disminuidos. Se reportó: amilasa 2163 U/L, lipasa 821 U/L, deshidrogenasa láctica 461 U/L. Ultrasonido de páncreas: cabeza de 19.3 mm, cuerpo de 23.2 mm y cola de 10 mm. Fue internada en pediatría, confirmándose páncreas anular por ultrasonido y tomografía; recibió tratamiento conservador. Conclusión: la paciente presentó síntomas típicos del páncreas anular, su estudio mediante imágenes fue decisivo para establecer el diagnóstico.

Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert.

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests-PBSn1 and an ancestry-enrichment test-in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10-9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.

Thromboembolic Events with Enterprise Versus Pipeline: Porcine In Vivo Experiment.

BACKGROUND: Thromboembolic complications are serious adverse events associated with stenting of intracranial aneurysms. For the development of novel devices, currently no practical model exists to evaluate distal embolic events. The purpose of the current study was 2-fold: 1) assess the feasibility of a porcine carotid bifurcation model for in vivo testing of stent thrombogenicity and 2) compare the thrombogenicity of the Enterprise vascular reconstruction device versus the Pipeline embolization device (PED). METHODS: Six Yorkshire pigs underwent implantation of size-matched devices across the carotid bifurcation. Each animal received 1 Enterprise and 1 PED contralaterally. Baseline and 2-week follow-up angiography were performed. Images were analyzed including detailed measurements of the rete mirabile, a small-vessel conglomerate supplied by branches of the common carotid artery. RESULTS: In the absence of thromboembolic events at 2 weeks (n = 8), the perfused rete area measured 134.4 ± 6.9 mm2. In the presence of thromboembolic events (n = 4), the perfused rete was reduced to an area covering 37.1 ± 8.6 mm2 (P < 0.01). There was no difference in thrombogenicity between Enterprise and PED with a thromboembolic event rate of 33.3% for both devices (P > 0.99). CONCLUSION: The swine carotid stent model allows in vivo analysis of device-related thrombogenicity and distal embolic event rates. Size reduction of the perfused rete mirabile indicates the presence of thromboembolic events. Both Enterprise and PED were associated with similar thrombogenicity in this experiment.