Flavivirus replication kinetics in early-term placental cell lines with different differentiation pathways.

BACKGROUND: The uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015-2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency. One of the most notable features of ZIKV pathogenesis was the ability of the virus to pass the placental barrier to infect the growing foetus. This pathogenic trait had not been observed previously for medically important flaviviruses, including dengue and yellow fever viruses. METHODS: In this study we evaluated the replication kinetics of ZIKV and the related encephalitic flavivirus West Nile strain Kunjin virus (WNVKUN) in early-term placental cell lines. RESULTS: We have observed that WNVKUN in fact replicates with a greater rate and to higher titres that ZIKV in these cell lines. CONCLUSIONS: These results would indicate the potential for all flaviviruses to replicate in placental tissue but it is the ability to cross the placenta itself that is the restrictive factor in the clinical progression and presentation of congenital Zika syndrome.

Adenovirus vector produced Zika virus-like particles induce a long-lived neutralising antibody response in mice.

Countermeasures against Zika virus (ZIKV) epidemics are urgently needed. In this study we generated a ZIKV virus-like particle (VLP) based vaccine candidate and assessed the immunogenicity of these particles in mice. The ZIKV-VLPs were morphologically similar to ZIKV by electron microscopy and were recognized by anti-Flavivirus neutralising antibodies. We observed that a single dose of unadjuvanted ZIKV-VLPs, or inactivated ZIKV, generated an immune response that lasted over 6 months, but did not neutralize ZIKV infection of cells in vitro. However, when we co-administered the ZIKV VLPs with either Aluminium hydroxide (Alhydrogel®; Alum), AddaVax or Pam2Cys we observed that Alum was the most effective in a single dose regime, since it not only produced antibodies that neutralized the virus, but also generated a greater number of antigen-specific memory B cells. We additionally observed that the generation of the neutralising antibodies persisted for up to 6 months. Our results suggest that a single dose ZIKV VLPs could be a suitable single dose vaccine candidate for use in outbreak settings.

A cross-sectional study of quantitative CT measurements associated with the diffusion capacity of the lung in recovered COVID-19 patients with normalised chest CT.

Impairment of the diffusion capacity of the lung for carbon monoxide (DLco) is commonly reported in convalescent and recovered COVID-19 patients, although the cause is not fully understood especially in patients with no radiological sequelae. In a group of 47 patients at 7 - 51 weeks post infection with either none or minimal scarring or atelectasis on chest CT scans (total < 0.1% of lung volume), dispersions in DLco-adj % and total lung capacity (TLC) % of predicted were observed, with median(quartiles) of 87(78, 99)% and 84(78, 92)%, respectively. Thirteen(27.1%) patients had DLco-adj% < 80%. Although the DLco-adj% did not significantly correlate with the severity of the illness in the acute phase, time since the onset of symptoms, the volume of residual lesions on CT, age or sex, DLco-adj/alveolar volume (Kco-adj) % predicted was correlated with the measurements of small blood vessel volume fraction (diameter <= 5mm) and parenchyma density on CT. Multivariate analysis revealed that these two CT metrics significantly contributed to the variance in DLco-adj% independent of TLC%. Comparing to between-subject variability of DLco-adj in healthy individuals, patients in this cohort with DLco-adj% < 80% were likely abnormal with a degree of disease not visually detectable on CT. However, it is not clear whether the associated variance of parenchyma density and small vessel volume fraction were a consequence of the COVID-19 disease or a pre-existing background variance.

Monocyte apoptotic bodies are vehicles for influenza A virus propagation.

The disassembly of apoptotic cells into small membrane-bound vesicles termed apoptotic bodies (ApoBDs) is a hallmark of apoptosis; however, the functional significance of this process is not well defined. We recently discovered a new membrane protrusion (termed beaded apoptopodia) generated by apoptotic monocytes which fragments to release an abundance of ApoBDs. To investigate the function of apoptotic monocyte disassembly, we used influenza A virus (IAV) infection as a proof-of-concept model, as IAV commonly infects monocytes in physiological settings. We show that ApoBDs generated from IAV-infected monocytes contained IAV mRNA, protein and virions and consequently, could facilitate viral propagation in vitro and in vivo, and induce a robust antiviral immune response. We also identified an antipsychotic, Haloperidol, as an unexpected inhibitor of monocyte cell disassembly which could impair ApoBD-mediated viral propagation under in vitro conditions. Together, this study reveals a previously unrecognised function of apoptotic monocyte disassembly in the pathogenesis of IAV infections.

Determinants of Zika virus host tropism uncovered by deep mutational scanning.

Arboviruses cycle between, and replicate in, both invertebrate and vertebrate hosts, which for Zika virus (ZIKV) involves Aedes mosquitoes and primates1. The viral determinants required for replication in such obligate hosts are under strong purifying selection during natural virus evolution, making it challenging to resolve which determinants are optimal for viral fitness in each host. Herein we describe a deep mutational scanning (DMS) strategy2-5 whereby a viral cDNA library was constructed containing all codon substitutions in the C-terminal 204 amino acids of ZIKV envelope protein (E). The cDNA library was transfected into C6/36 (Aedes) and Vero (primate) cells, with subsequent deep sequencing and computational analyses of recovered viruses showing that substitutions K316Q and S461G, or Q350L and T397S, conferred substantial replicative advantages in mosquito and primate cells, respectively. A 316Q/461G virus was constructed and shown to be replication-defective in mammalian cells due to severely compromised virus particle formation and secretion. The 316Q/461G virus was also highly attenuated in human brain organoids, and illustrated utility as a vaccine in mice. This approach can thus imitate evolutionary selection in a matter of days and identify amino acids key to the regulation of virus replication in specific host environments.

Efecto de la rehabilitación en la calidad de vida de personas con lesión medular / Effect of rehabilitation on the quality of life of people with spinal cord injury

RESUMEN Introducción. La rehabilitación de las lesiones medulares (LM) busca la reinserción social de las personas afectadas y evalúa sus limitaciones según el grado de discapacidad. Objetivo. Determinar el efecto del programa de rehabilitación en la calidad de vida de personas con lesión medular. Métodos. Estudio analítico, observacional, prospectivo y longitudinal. Participaron personas con diagnóstico de lesión medular completa e incompleta de nivel cuadripléjico y parapléjico, masculino y femenino, entre 14 y 80 años, de etiología traumática y no traumática, y tiempo evolución menor de 10 años. Resultados. Se seleccionaron 65 personas como muestra censal que estuvieron hospitalizados en el período enero-junio 2017. La característica clínica más frecuentes fueron el nivel parapléjico ASIA A con el 30,8%, de etiología traumática con el 72,3% y con tiempo de evolución mayor de 3 años en el 40%. Se encontraron diferencias entre la calidad de vida inicial y final de los componentes físico y mental (p=0,001). Todas las escalas de los componentes físico y mental de la calidad de vida de inicio y fin también fueron significativas (p=0,001). Conclusiones. La calidad de vida en los componentes físico y mental mejoró en las personas con lesión medular al término de la rehabilitación. Hubo cambios positivos de la calidad de vida en el componente mental en el nivel parapléjico y de etiología no traumática; en las personas lesión medular incompleta ASIA C, también se encontró cambios de la calidad de vida en el componente físico.

ABSTRACT Introduction. The rehabilitation of spinal injuries (LM) seeks the social reintegration of the affected people, and assesses their limitations according to the degree of disability. Objective. To determine the effect of a rehabilitation program on quality of life of people with spinal cord injury. Methods. An analytical, observational, prospective and longitudinal study. People with a diagnosis of complete and incomplete spinal cord lesion at the quadriplegic and paraplegic level, male and female, between 14 and 80 years old, of traumatic and non-traumatic etiology and evolution time of less than 10 years were selected. Results. 65 people were selected as census sample who were hospitalized in the period january-june 2017. The most frequent clinical characteristics were the ASIA A paraplegic level with 30,8%, traumatic etiology with 72,3% and a time of evolution greater than 3 years, in 40%. Initial and final quality of life of the physical and mental components were found to be significant (p=0,001), all scales of the physical and mental components of the quality of life at the beginning and end were also significant (p=0,001). Conclusions. An improvement of quality of life, in physical and mental components, were founded in people with spinal cord injury at the end of the rehabilitation. There were positive changes in the quality of life in the mental component at the paraplegic level and in nontraumatic etiology. Changes in quality of life in the physical component were also found in people with incomplete spinal cord injury ASIA C.

Efecto de la fisioterapia en un paciente con neurofibromatosis tipo II: Reporte de un caso / Effect of physiotherapy in a patient with neurofibromatosis type II: A case report

La fisioterapia en pacientes con lesión neurológica degenerativa puede mejorar la capacidad funcional permitiéndole una participación social activa y una mejor calidad de vida mientras la evolución de la enfermedad lo permita. Se describe los efectos de la fisioterapia en un paciente con lesión medular secundaria a Neurofibromatosis tipo II. La intervención se basó en terapias cardiorrespiratoria, funcional y deportiva. Se obtuvo en el paciente mayor funcionalidad para caminar, mejor autoestima y capacidad física para trabajar. (AU)

Physiotherapy in patients with degenerative neurologic conditions may improve functional capacity allowing a better quality of life and active social participation, as long as the progression of disease allows it. We report the effects of physiotherapy in a patient with medullar involvement due to type II neurofibromatosis. Interventions were based on cardiorespiratory, functional and sport interventions. The intervention attained better functionality to walk, better self-confidence and physical capacity to work. (AU)

Efecto de la fisioterapia en un paciente con cuadriplejia por ependimoma medular / Effect of physiotherapy in a patient with quadriplegia due to a medullar ependymoma

La fisioterapia en pacientes con problemas neorológicos, mejora la capacidad funcional identificando limitaciones provocadas por la lesión aplicando técnicas kinésicas. Se describe los efectos de la fisioterapia en un paciente con cuadriplejía secundaria a ependimoma medular que no recibió tratamiento quirúrgico. La regulación del tono postural favoreció el control postural y el equilibrio en actividades en sedente y en cama. Se obtuvo independencia funcional en actividades básicas de la vida diaria...

Physiotherapy improves functional capacity in patients with neurologic involvement, identifying limitations induced by neurologic lesions and applying kinetic techniques. We describe the effects of physiotherapy in a patient with medullar ependymoma that did not undergo surgical intervention. Physiotherapy improved postural control and equilibrium achieving independent functionality in basic daily activities...

Una década de altas médicas no efectivizadas en un hospital de Lima, Perú / A decade of no effective inpatient medical discharges, experience from a hospital in Lima, Peru

El objetivo del estudio fue describir los cambios financieros de los días de alta no efectiva desde el año 2001 al 2010, en un hospital general de Lima Metropolitana. Para ello, se obtuvieron los montos totales pagados y exonerados de las cuentas de los pacientes con alta médica no efectivizada, por falta de pago del hospital general. Encontramos que el número de pacientes con alta médica no efectivizada por falta de pago disminuyó del 2001 al 2010 en 77 por ciento, los días desde el alta médica hasta que el paciente abandonó el hospital disminuyeron en 80 por ciento; las cuentas totales, pagadas y exoneradas, se redujeron en 63, 53 y 68 por ciento respectivamente. Asimismo, el porcentaje promedio exonerado a cada paciente con alta médica no efectivizada por falta de pago, en la década estudiada, fue 61,7 por ciento. En conclusión, el alta no efectiva incrementa los costos al paciente, teniendo que ser asumido por el hospital al exonerar la cuenta, aunque este gasto disminuyó en el periodo estudiado, esto podría deberse a la implementación de políticas de aseguramiento en salud

Our aim is to describe the financial implications of no effective in patient discharges from 2001-2010 from a general hospital in lima city. For this purpose we analyzed the total amounts, cancellations and exonarations from the patient accounts with a non effective medical discharge because of hospital “debts”. We found that the number of patients with a non effective medical discharge decreased 70% from 2001 to 2010, the number of days between the medical discharge until the day the patient left the hospital decreased 80%. The total amounts, cancellations and exonarations decreased 63%, 53% and 68%, respectively. The average amount of exoneration was 61,7%. In conclusion, the non effective medical discharges increase patient debts, which are partially exonerated and assumed by the hospital. Even though it has decreased in the last decade, this could be explained by the implementation of the new health insurance policies.

Sobrevida en hemodiálisis según el periodo de ingreso de pacientes entre 1982 y 2007 en Lima, Perú / Survival in hemodialysis as the period of admission of patients between 1982 and 2007 in Lima, Peru

La hemodiálisis desde la década del 1970 ha sufrido grandes variaciones tecnológicas, organizacionales y conceptuales. Objetivo: Evaluar la supervivencia de pacientes en hemodiálisis en función del periodo de inicio de su tratamiento. Material y métodos: Estudio de cohortes retrospectivo no concurrente de dos grupos de pacientes que iniciaron hemodiálisis antes de 1995 (Grupo 1) y después de 1995 (Grupo 2), pareados para edad, sexo y etiología de enfermedad renal crónica terminal (ERCt). Resultados: Se Incluyeron 179 pacientes en el grupo 1, (prescripción KT/V = 1,0) y 180 pacientes en el grupo 2 (prescripción KT/V > 1,2). No hubo diferencia estadística en la sobrevida de los pacientes en función del periodo de inicio de hemodiálisis (mediana ± ES: 7,2 ± 2,38 años para el grupo 1 y mediana ± ES: 7,4 ± 1,49 años para el grupo 2). La supervivencia al 1er y 5to año fue 0,87 ± 0,026 y 0,54±0,047 para el grupo 1; y 0,86 ± 0,028 y 0,62 ± 0,051 para el grupo 2. Las diferencias no fueron estadísticamente significativas. Conclusión: No hubo diferencia en la sobrevida entre los dos grupos estudiados.

Hemodialysis since the 1970s has undergone major technological, organizational and conceptual changes. Objective: To assess the survival probability of patients who have entered a hemodialysis program in relation to the time of their treatment beginning. Material and methods: A retrospective non concurrent cohort study of two groups of patients admitted to hemodialysis before1995 (Group 1) and after 1995 (Group 2), matched for age, sex and etiology of end stage renal disease (ESRD). Results: We selected 179 patients in group 1 (prescription KT/V = 1.0) and 180 patients in group 2 (prescription KT/V > 1. 2). There was no statistical difference in the survival of patients based on the year of admission to hemodialysis (median ± SE: 7.2 ± 2.38 years for Group 1 and median ± SE: 7.4 ± 1.49 years for Group 2). The one and five year survival was 0.87 ± 0.026 and 0.54 ± 0.047 for Group 1; and 0.86 ± 0.028 and 0.62 ± 0.051 for group 2. The difference was not statistically significant. Conclusion: There was no difference in survival in the two groups studied.

Examen nacional de medicina en Perú 2008 - 2009: análisis y sostenibilidad de los resultados / National medicine examination in Peru 2008-2009: analysis and sustainability of results

Objetivo: Analizar la consistencia de los resultados del ENAM 2008 y 2009. Material y método: Con datos oficiales publicados de los resultados del ENAM 2008 y 2009 se exploró la consistencia entre los resultados generales y parciales obtenidos por las diferentes universidades definidas como estatales y privadas de Lima u otra ciudad. Se analizó los resultados considerando los puntajes obtenidos como variables numéricas y ordinales (cuando se consideró el orden en función de los ordenamientos parciales que dieron como resultado el orden jerárquico final). Se aceptó como significancia estadística p<0,05. Resultados: La correlación fue buena (r>0,90) entre el orden según el puntaje general y el orden jerárquico en los dos períodos estudiados, siendo mejor en el 2008. La correlación entre el orden jerárquico obtenido en ambos años estudiados fue pobre pero estadísticamente significativa (r=0,69, p<0,001). La consistencia de los resultados parciales de las universidades entre el 2008 y 2009 fue inexistente excepto en el área de pediatría. Los resultados fueron diferentes en función de ser universidad estatal o privada (en el puntaje general y en el área de medicina) y en función de ser de Lima o de otra ciudad (en áreas de ginecología-obstetricia y salud pública). El modelo de ser universidad estatal y de Lima mostró un comportamiento diferente a otras combinaciones. Conclusión: Los resultados obtenidos por las universidades en los ENAM de los años 2008 y 2009 mostraron pobre consistencia. Los resultados mostraron un comportamiento diferente de las universidades estatales y de Lima en relación a otras combinaciones.

Objective: To assess the consistency of the results of the National Medicine Exam (NME) in Peru for years 2008 and 2009. Material and method: We examined consistency between general and partial results obtained by the different public and private medical schools from Lima or other cities using official published data regarding the results of NME in Peru for years 2008 and 2009. These results were analyzed taking into account both numerical scores and ordinal variables (when considering the order on the basis of partial results that resulted in the final rank order). Statistical significance was established in p<0.05. Results: The correlation was good (r>0.90) between the order considering the overall score and rank order in the two periods studied, but the best result was obtained in 2008. The correlation between the Rank order obtained in both years was low, with a statistically significant result(r=0.69, p<0.001). The consistency of partial results from universities between 2008 and 2009 was non-existent except in the pediatrics area. The results were different in terms of coming from a public or a private university (both in the overall score and in the medicine area) and being based in Lima or another city (for obstetrics and gynecology and public health items). The model consisting in being a public medical school based in Lima showed a different behavior compared to other variable combinations. Conclusion: NME results in years 2008 and 2009 showed poor consistency. The results showed a different behavior of public Lima/based medical schools compared with other variable combinations.