Anti-SpCas9 IgY Polyclonal Antibodies Production for CRISPR Research Use.

The CRISPR/Cas adaptative immune system has been harnessed as an RNA-guided, programmable genome editing tool, allowing for diverse biotechnological applications. The implementation of the system relies on the ability to detect the Cas9 protein in biological samples. This task is facilitated by employing antibodies, which exhibit several advantageous features and applications in the context of tropical neglected diseases. This study reports a one-month immunization scheme with the Cas9 protein fromStreptococcus pyogenes to produce IgY polyclonal antibodies (anti-SpCas9), which can be rapidly isolated by combining yolk de-lipidation with protein salting out using pectin and ammonium sulfate, respectively. Immunodetection assays indicate that the antibodies are highly sensitive, specific, and useful for detecting the SpCas9 protein in promastigotes ofLeishmania braziliensisexpressing exogenous SpCas9. Thus, the simple method for producing anti-SpCas9 IgY antibodies will accelerate CRISPR/Cas-based studies in Leishmania spp. This approach serves as a valuable research tool in this parasite model and holds the potential for wide application in various other biological samples, promoting the implementation of the system. In fact, a bioinformatics approach based on the identification of antigenic determinants in the SpCas9 protein suggests the possibility of using the anti-SpCas9 IgY antibodies in applications such as Prime and Base editing.

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Biologically synthesized silver nanoparticles as potent antibacterial effective against multidrug-resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.

Otorrea por uso de audífonos en pacientes con otitis media crónica / Otorrhea due to hearing aids use in patients with chronic otitis media

Resumen Introducción: La presencia de otorrea es un indicador de actividad en otitis media crónica (OMC), además de influir en la calidad de vida. La oclusión del molde de un audífono generaría incremento de otorrea, por esto se acostumbra a evitarla en estos casos. La relación otorrea/audífono en OMC no ha sido adecuadamente estudiada. Objetivo: Comprobar si se produce incremento en frecuencia y/o gravedad de episodios de otorrea por el uso de audífono en OMC simple. Caracterización clínica-demográfica de la muestra. Material y Método: Estudio prospectivo antes/después en pacientes con diagnóstico de OMC simple que se implementen con audífono. Entrevista telefónica para caracterizar episodios de otorrea en relación con el audífono. Resultados: Fueron evaluados 35 oídos en 34 pacientes, edad promedio 66,6 años. Sin diferencias significativas en aparición de otorrea y consultas por otorrea antes y después de la implementación. El grupo diagnóstico OMC supurada correspondió al 28,6%, OMC supurada seca el 11,4% y OMC inactiva 60%. Diferencias significativas comparando otorrea posimplementación en subgrupo OMC supurada con resto de subgrupos (p < 0,0001). Análisis multivariado de regresión logística confirmó que sólo OMC supurada se asoció a otorrea posimplementación (p < 0,004). Conclusión: Tradicionalmente se correlaciona uso de audífono en OMC con incremento de otorrea. Nuestro estudio no evidenció diferencias después de la implementación: pacientes con otorrea previa al audífono siguieron presentándola de la misma manera y pacientes con oído seco se mantuvieron así. Otorrea al implementar es el único factor predictor de otorrea por audífono. Debe realizarse más investigación, con evaluación presencial e incorporando variables.

Abstract Introduction: Otorrhea is a chronic suppurative otitis media (CSOM) activity indicator, affecting quality of life. Hearing aid mold occlusion would increase otorrhea, so it is usual to avoid it. Otorrhea/hearing aid relationship in CSOM has not been properly studied. Aim: To check for an increase in frequency and/or severity of otorrhea episodes in CSOM due to hearing aid use. Clinical-demographic characterization of the sample. Material and Method: Prospective before/after study, in CSOM diagnosed patients using a hearing aid. Telephone interview to characterize otorrhea episodes due to hearing aid use. Results: 35 ears were evaluated in 34 patients, with a mean age of 66.6 years. There were no significant differences before and after hearing aid implementation in otorrhea episodes and medical consultations. 28.6% corresponded to active CSOM diagnosis group, 11.4% partially-active CSOM and 60% inactive CSOM. We found significant differences observed between active CSOM subgroup and the rest by comparing post-hearing aid implementation otorrhea (p < 0.0001). Only active CSOM diagnosis was associated to post-hearing aid implementation otorrhea by multivariate logistic regression analysis (p < 0.004). Conclusion: Traditionally, hearing aid use is correlated with increase in otorrhea in CSOM. In our study there were no differences before and after hearing aid implementation: patients with previous otorrhea continued presenting it in the same way after hearing aid use and patients with dry ear kept it that way. The only predicting factor of otorrhea due to hearing aid use is active otorrhea at implementation. Further investigation should be done, with face-to-face evaluation and incorporating variables.

Comparación de sutura mecánica con sutura manual de la faringe en laringectomía total / Comparison of mechanical suture with manual suture of the pharynx in total laryngectomy

Introducción: La sutura mecánica es una opción para el cierre de la faringorrafia en laringectomía total por cáncer de laringe. Objetivo: Comparar el uso de sutura mecánica lineal con sutura manual de la faringe durante la laringectomía total por cáncer de laringe. Material y Método: Se realizó un estudio de tipo experimental prospectivo. Se compararon dos grupos pacientes: Los pacientes con sutura mecánica desde 2018 a marzo de 2020 y los pacientes con sutura manual previa a enero de 2018 en el Servicio de Otorrinolaringología del Hospital Barros Luco. Se analizaron fístula faringo-cutánea posoperatoria (FFC), tiempo operatorio, estadía hospitalaria y costo. Resultados: El estudio incluyó a 14 pacientes, cada grupo con n = 7. El grupo con sutura mecánica presento 0% de FFC y el grupo sutura manual 28%. El grupo con sutura mecánica reinicio alimentación a los 7 días y el grupo con sutura manual en promedio a los 11,5 (7-23) días. (p = 0,0023). El tiempo promedio de cirugía para el grupo experimental es de 288 ± 37,4 minutos y con sutura manual 311 ± 32,4 minutos. (p = 0,0176). El promedio de hospitalización para el grupo experimental fue de 11 ± 2,6 días (9 a 16), y para el grupo control fue de 21 ± 14 días (10 a 49) (p < 0,0001). Conclusión: La sutura mecánica es un procedimiento fácil de usar y seguro. Existiría un beneficio en el uso de sutura mecánica para el cierre faríngeo al compararlo con la sutura manual al disminuir el número de FFC, el tiempo operatorio y los días de hospitalización.

Introduction: Mechanical suture is an option for the closure of the pharyngorrhaphy in total laryngectomy due to laryngeal cancer. Aim: To compare the use of linear mechanical suture with manual pharyngeal suture during total laryngectomy for laryngeal cancer. Material and Method: A prospective experimental study was carried out. Two patient groups were compared: patients with mechanical suture from 2018 to March 2020 and patients with manual suture prior to January 2018 at the otorhinolaryngology service of the Barros Luco Hospital. Postoperative pharyngocutaneous fistula (FFC), operative time, hospital stay and cost were analyzed. Results: The study included 14 patients, each group with n = 7. The group with mechanical suture presented 0% of FFC and the group with manual suture 28%. The group with mechanical suture restarted feeding at 7 days and the group with manual suture on average at 11.5 (7-23) days (p = 0.0023). The average surgery time for the experimental group was 288 ± 37.4 minutes, while for the group with manual suture was 311 ± 32.4 minutes (p = 0.0176). The mean hospitalization for the experimental group was 11 ± 2.6 days (9 to 16), and for the control group it was 21 ± 14 days (10 to 49) (p < 0.0001). Conclusion: The mechanical suture is an easy to use and safe procedure. There would be a benefit in the use of mechanical suture for pharyngeal closure when buying it with manual suture by reducing the number of FFCs, operative time and days of hospitalization.

Rol protector de N-acetilcisteína en la ototoxicidad inducida por cisplatino en pacientes con cáncer de cabeza y cuello. Ensayo clínico controlado aleatorizado

Resumen Introducción: La ototoxicidad por cisplatino es un evento muy frecuente y sus consecuencias producen mucho deterioro en los pacientes. El diagnóstico precoz es esencial, pues permitiría implementar apropiadamente estrategias para aminorar su efecto. Entre estas tenemos la N-acetilcisteína, un agente antioxidante que ha demostrado efecto otoprotector. Objetivo: Evaluar el rol otoprotector de N-acetilcisteína comparado con placebo, en pacientes con cáncer de cabeza y cuello tratados con cisplatino. Material y Método: Ensayo clínico aleatorizado, paralelo y controlado con placebo. Se incluyen pacientes con cáncer de cabeza y cuello que requieren tratamiento con cisplatino, dos ramas: un grupo control que recibe placebo y otro que recibe el fármaco. Se realizan audiometrías de altas frecuencias (6-16 kHz) antes, durante y una vez finalizado el tratamiento. Resultados: Se aleatorizaron 45 pacientes, 23 al grupo intervencional y 22 al grupo control. Se encontró una incidencia general de la ototoxicidad del 73%, un empeoramiento en relación con tiempo de medición, una detención y estabilización del efecto ototóxico en el grupo que recibió N-acetilcisteína, todas estas diferencias fueron significativas. Conclusión: La N-acetilcisteína no previene la ototoxicidad inducida por cisplatino, pero modifica su curso de instalación y progresión. No se registraron efectos adversos al uso del fármaco. El monitoreo audiológico precoz es esencial para identificar la ototoxicidad y ejercer acciones para modificar su curso y mejorar la calidad de vida.

Abstract Introduction: Cisplatin-induced ototoxicity is a very frequent event and its consequences can cause a lot of deterioration in patients. There are some strategies to reduce its effect, among these, N-acetylcysteine, an antioxidant agent, has shown otoprotective effect. Aim: To evaluate the effect of N-acetylcysteine on ototoxicity by chemotherapy-radiotherapy in patients with head and neck cancer, compared with placebo. Material and Method: Randomized, parallel design and placebo controlled clinical trial. Patients with head and neck cancer who require treatment with cisplatin were enrolled: a control group that receives a placebo and experimental group that receives the drug. High-frequency audiometries were performed before, during and after the treatment finalization. Results: Forty-five patients were randomized, 23 for the experimental group and 22 for control group. The investigators found an incidence of ototoxicity of 73%, a worsening in relation to the time of measurement and a stopping and stabilization of the ototoxic effect in the group that received N-acetylcysteine, all these differences were statistically significant. Conclusion: N-acetylcysteine does not prevent cisplatin-induced ototoxicity, but does modify its course of installation and progression. No adverse effects were registered in this trial. Early audiological monitoring is essential to identify ototoxicity and eventually modify its course and improve the quality of life.

Actualización en carcinoma escamoso orofaríngeo

Resumen El carcinoma escamoso de orofaringe (CEOF) ha tenido un aumento en su incidencia en las últimas décadas, explicándose por el aumento sustancial de su tipo relacionado con el virus papiloma humano (VPH). Existen diferencias clínicas y pronósticas entre los dos grupos de CEOF según su relación etiológica con VPH. Por un lado, los relacionados con VPH se presentan en una población más joven, con menos prevalencia de tabaquismo y consumo de alcohol; además de presentar un tamaño pequeño del tumor primario, con un compromiso linfonodal temprano. Además, aquellos relacionados con VPH presentan un mejor pronóstico que su contraparte no relacionada con el virus, presentando en algunos estudios hasta un 58% menos riesgo de muerte independiente de la modalidad de tratamiento. Actualmente, el sistema de clasificación TNM en su 8va edición presenta un sistema diferente de clasificación y etapificación para ambos grupos. A pesar de aquello, a la fecha el tratamiento habitual no difiere entre ambos, lo que ha llevado a la realización de estudios que buscan responder si la deintensificación de la terapia en aquellos grupos relacionados con VPH y con bajo riesgo de metástasis a distancia, mantendría los buenos resultados oncológicos, disminuyendo las complicaciones a corto y largo plazo asociadas al tratamiento. Sin embargo, aún no existe evidencia que avale consistentemente esta práctica. Finalmente, la prevención primaria a través de la vacuna contra VPH es un elemento prometedor, sin embargo, no existe evidencia que confirme su utilidad.

Abstract Oropharyngeal squamous cell carcinoma (OPSCC) has suffered an increase in its incidence in recent decades, explained by the increase in its type related to the human papilloma virus (HPV). There are clinical and prognostic differences between the two groups of OPSCC according to their etiological relationship with HPV. On the one hand, those related to HPV appear in a younger population, with a lower prevalence of smoking and alcohol consumption; in addition to presenting a small size of the primary tumor, with early lymph node involvement. Furthermore, those related to HPV have a better prognosis than their non-virus counterpart, presenting in some studies up to 58% less risk of death, independent of treatment used. Currently, the TNM classification system in its 8th edition presents a different classification for both groups. Despite this, the treatment does not differ between the two, which has led to studies that seek to answer whether the de-escalation of therapy in the group associated to HPV and with a low risk of distant metastasis would maintain the reported good oncological results, reducing early and long-term complications associated with treatment, however, there is still no evidence to support its use. Finally, primary prevention through the HPV vaccine is a promising element, however there is no evidence to confirm its usefulness.

Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains.

AIM: As options to treat recalcitrant bacterial infections which are increasingly limited due to multidrug-resistant strains, searching for new, effective antibacterial compounds is necessary. One strategy is to generate treatment alternatives by drug repurposing. METHODS AND RESULTS: In this work, phenotypic microarrays were used for the screening of miscellaneous compounds against the growth and biofilm formation of Acinetobacter baumannii, an important emergent multidrug-resistant opportunistic pathogen. The results showed that the phenothiazine derivatives, such as promethazine, trifluoperazine, thioridazine, and chlorpromazine, inhibited the growth of antibiotic-sensitive and multidrug-resistant strains (showing minimal inhibitory concentrations ranging from 0·05 to 0·6 g l-1 and minimal bactericidal concentrations ranging from 0·1 to 2·5 g l-1 ). All phenothiazine derivatives were active against biofilm cells (with minimal biofilm eradication concentrations ranging from 0·5 to >3 g l-1 ). Chlorpromazine promoted reactive oxigen species (ROS) production, and cell membrane and DNA damage. Chlorpromazine showed synergy with antibiotics such as ceftazidime, meropenem, and colistin and was an effective treatment for experimentally infected Galleria mellonella when combined with ceftazidime. CONCLUSIONS: It was demonstrated that phenothiazine derivatives, especially chlorpromazine, are drugs with attractive antibacterial properties against nosocomial MDR strains of A. baumannii, by generating ROS and cell membrane and DNA damage. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicates that repurposing phenothiazine derivatives for treating recalcitrant infections by A. baumannii could be promising.

Colgajo en isla submental: Experiencia de 2 casos en reconstrucción de base de cráneo lateral

Resumen La cirugía reconstructiva de cabeza y cuello es una tarea compleja. Existen varias opciones disponibles para lograr buenos resultados, desde colgajos locales hasta colgajos libres microvascularizados. En este reporte presentamos nuestra experiencia utilizando el colgajo en isla submental para la reconstrucción de defectos de tejido blando de base de cráneo lateral posterior a una resección lateral de hueso temporal secundario a diagnósticos oncológicos otológicos. Se presentan datos demográficos, clínicos, quirúrgicos y resultados de dos pacientes intervenidos durante el primer semestre del año 2020, en los cuales se consiguió un adecuado resultado reconstructivo. Este colgajo es una opción confiable y versátil para reconstrucción en cabeza y cuello.

Abstract Reconstructive head and neck surgery is a complex task. There are several options available to achieve good results, from local flaps to free microvascular flaps. In this article, we present our experience using the submental island flap for soft tissue defect reconstruction of the lateral skull base after a lateral temporal bone resection secondary to otologic cancer. Demographic, clinical, surgical and outcome data of two patients operated on during the first semester of 2020 are presented, in whom a good reconstructive result was achieved. This flap is a reliable and versatile option for head and neck reconstruction.

Bacteria cultured from the gut of Meccus pallidipennis (Hemiptera: Reduviidae), a triatomine species endemic to Mexico.

The study of intestinal microbiota in vector insects like triatomines is paramount in parasitology because many parasitic species inhabit the vector's gut. Although knowledge on the gut microbiota in various vectors of the parasitic flagellate Trypanosoma cruzi has grown, research efforts have focused on South American triatomines. This study reports the isolation of bacterial microbiota in the anterior and posterior gut of Meccus pallidipennis (a triatomine species endemic to Mexico) by culture, as well as its identification by phenotypic and biochemical tests and its quantification by counting colony-forming units. The study was performed on fifth-instar nymph and adult specimens of M. pallidipennis, either laboratory-bred or collected in the field and either infected or not with T. cruzi. Overall, 17 bacterial species were identified, with the genera Bacillus and Staphylococcus being the most prevalent regardless of the origin of the insects. No differences were observed in the number of bacterial species in the gut of laboratory-bred and field-collected insects, neither with respect to life stage or infection status. In general, the Shannon-Weaver diversity index was higher in non-infected insects than in infected ones. Further studies using non-culture methods are required to determine whether bacterial species diversity is modified by laboratory breeding.

Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients.

INTRODUCTION: No therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. METHOD: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions. RESULTS: Patients with TCZ (n=20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P=0.014), presented with more severe forms (higher level of oxygen therapy at 13L/min vs 6L/min, P<0.001), and had poorer biological findings (severe lymphopenia: 676/mm3 vs 914/mm3, P=0.037 and higher CRP level: 158mg/L vs 105mg/L, P=0.017) than patients without TCZ (n=25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P=0.002). CONCLUSION: Despite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.

Resultados de un programa de recuperación mejorada (PRM) en cirugía colorrectal: efectos en la estadía hospitalaria / Shortening of hospital length of stay after the implementation of an Enhanced Recovery Program for elective colorectal surgery

Resumen Introducción Los Programas de Recuperación Mejorada (PRM) en cirugía colorrectal disminuyen las complicaciones y acortan la estadía hospitalaria. La implementación de un PRM representa un desafío en nuestro sistema de salud público, dado la alta demanda y recursos limitados. Objetivo Evaluar el efecto en la estadía hospitalaria (EH) posterior a la implementación de un PRM en cirugía colorrectal electiva en un hospital público. Materiales y Método Estudio retrospectivo, que incluyó pacientes entre 15 y 85 años operados electivamente de resecciones colorrectales en un hospital público entre 1 de enero de 2015 y 31 de diciembre de 2016. Se compararon dos grupos: 1) total de pacientes operados electivamente 1 año posterior a la implementación del PRM (post-PRM) y 2) total de pacientes operados electivamente un año previo a la implementación de PRM (pre-PRM), en términos de EH, reingresos, complicaciones y mortalidad a 30 días. Se realizó análisis de tiempo a evento para comparar la EH entre ambos grupos. Resultados Un total de 144 pacientes fueron incluidos: 92 en el grupo post-PRM y 52 en el grupo pre-PRM. No hubo diferencias clínicas entre ambos grupos. La mediana de EH en el grupo post-PRM fue 2 días menor que en el grupo control (5 vs 7 días, test de log-rank, p = 0,03). No hubo diferencia en complicaciones, reingresos ni mortalidad. Conclusión La implementación de un PRM en cirugía colorrectal electiva en un hospital público se asocia a una disminución de la EH sin aumento de morbimortalidad.

Background Enhanced Recovery Programs (ERP) in colorectal surgery has proved to decrease complications and shorten hospital stay. The implementation of an ERP could be a difficult task in a high-demanding public health system with limited resources. Aim Evaluate the effect on length of stay (LOS) after the implantation of an ERP for colorectal surgery in a resource-limited public hospital. Materials and Method This retrospective study included patients aged 15-85 years who underwent elective colorectal surgery at a resource-limited public hospital in Chile between January 1, 2015 and December 31, 2016. We compared two groups: (1) total number of patients operated electively after 1-year of ERP implementation (post-ERP group) and (2) total number of patients electively operated 1-year previous ERP (pre-ERP group) in terms of LOS, readmissions, complications, and 30-day mortality. A time to event analysis was performed to evaluate differences in LOS. Results A total of 144 patients were included in this study: 92 in the post-ERP group and 52 in the pre-ERP group. There were no clinical differences between groups. The median LOS in the post-ERP group was 2 days lower than that in the control group (5 vs 7 days, log-rank test p = 0.03). There were no differences in complications, readmissions, and 30-day mortality. Conclusions The implementation of an ERP for colorectal surgery in a resource-limited hospital was associated with decreased LOS without increasing morbidity.

Assessing virus infection probability in an office setting using stochastic simulation.

Viral infections are an occupational health concern for office workers and employers. The objectives of this study were to estimate rotavirus, rhinovirus, and influenza A virus infection risks in an office setting and quantify infection risk reductions for two hygiene interventions. In the first intervention, research staff used an ethanol-based spray disinfectant to clean high-touch non-porous surfaces in a shared office space. The second intervention included surface disinfection and also provided workers with alcohol-based hand sanitizer gel and hand sanitizing wipes to promote hand hygiene. Expected changes in surface concentrations due to these interventions were calculated. Human exposure and dose were simulated using a validated, steady-state model incorporated into a Monte Carlo framework. Stochastic inputs representing human behavior, pathogen transfer efficiency, and pathogen fate were utilized, in addition to a mixed distribution that accounted for surface concentrations above and below a limit of detection. Dose-response curves were then used to estimate infection risk. Estimates of percent risk reduction using mean values from baseline and surface disinfection simulations for rotavirus, rhinovirus, and influenza A infection risk were 14.5%, 16.1%, and 32.9%, respectively. For interventions with both surface disinfection and the promotion of personal hand hygiene, reductions based on mean values of infection risk were 58.9%, 60.8%, and 87.8%, respectively. This study demonstrated that surface disinfection and the use of personal hand hygiene products can help decrease virus infection risk in communal offices. Additionally, a variance-based sensitivity analysis revealed a greater relative importance of surface concentrations, assumptions of relevant exposure routes, and inputs representing human behavior in estimating risk reductions.

Nódulos subcutáneos como manifestación de cisticercosis diseminada / Subcutaneous nodules as manifestation of disseminated cysticercosis

RESUMEN Antecedentes: La cisticercosis es una infección parasitaria causada por la TaeniaSolium. Puede presentar una forma diseminada con compromiso sistémico. Clínicamente, la cisticercosis diseminada puede debutar con la presencia de nódulos subcutáneos. Presentamos un caso de diagnóstico de cisticercosis diseminada con la presencia de nódulos subcutáneos y síntomas respiratorios como única fuente de sospecha de enfermedad. Caso: Se presenta el caso de un paciente varón de 76 años de edad procedente de una región del Centro del Perú que acude a emergencia por hemoptisis, baja de peso y astenia de un año de evolución. Presentaba además nódulos subcutáneos no dolorosos, móviles en miembros superiores, inferiores, tórax, abdomen, cuello y cara. En la biopsia se demostró la presencia de cisticercocelullosae. Fue tratado con albendazol 400mg cada 12 horas por 6 meses, con evolución favorable. Conclusión: La cisticercosis es una enfermedad prevalente en nuestro país. Su presentación diseminada, sin embargo, no es tan frecuente. El diagnóstico puede ser difícil y a veces permanecer oculto, pues la clínica varía de silente a formas graves, dependiendo del órgano afectado, que en una forma diseminada pueden ser múltiples los órganos afectados, como el caso de nuestro paciente. Se concluye que las presencias de nódulos subcutáneos deben hacernos pensar en la posibilidad de formas diseminadas de cisticercosis.

ABSTRACT: Cysticercosis is a parasitic infection caused by Taenia Solium. It can be present as a disseminated form with systemic compromise. Disseminated cysticercosis may clinically debut with the presence of subcutaneous nodules. We present a case of diagnosis of disseminated cysticercosis with the presence of subcutaneous nodules and respiratory symptoms as the only source of suspected disease. Case: We present the case of a 76-year-old male patient from a region of central Peru who came to emergency due to hemoptysis, low weight and asthenia of one year of evolution. It also presented subcutaneous nodules that were painless, mobile in upper and lower limbs, abdomen, neck and face, the biopsy demonstrated with the presence of cysticercuscelullosae. He was treated with albendazole 400mg every 12h for 6 months, with favorable evolution. Conclusion: Cysticercosis is a prevalent disease in our country. Its disseminated presentation, however, is not as frequent. Diagnosis can be difficult and sometimes remain hidden, as the clinic varies from silent to severe, depending on the affected organ, which in a disseminated form can be multiple, as in the case of our patient. We conclude that the presence of subcutaneous nodules should make us think about the possibility of disseminated forms of cysticercosis.

Correction to: Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

The original version of the article unfortunately contained an error in the author group. Dr. Isabel Larré was not submitted and published in the original version.

Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.

Studies made in the Madin-Darby canine kidney (MDCK) epithelial cell line showed that ouabain regulates cell adhesion and cell-adhesion-related biological processes, such as migration. Here, we demonstrated that 10 nM ouabain accelerates collective cell migration and heals wounds in cultured MDCK cell monolayers. Ouabain-induced acceleration of cell migration depends on activation of the cSrc-ERK1/2 signaling cascade, as it was inhibited by the kinase inhibitors PP2 and PD98059. Activation of the cSrc-ERK1/2 signaling cascade increased expression and activation of the extracellular matrix metalloproteinase-2 (MMP-2). Inhibition of MMP activity using the generic inhibitor GM6001 or the potent iMMP-2 inhibitor prevented the accelerative effect of ouabain. Likewise, Focal Adhesion Kinase (FAK) inhibition with the transfection of dominant negative peptide FRNK impaired the effect of ouabain. These results suggest that ouabain binding to the Na+,K+-ATPase accelerates collective migration of MDCK cells through activation of the cSrc-ERK1/2-FAK signaling cascade and promoting secretion and MMP activity.

Impact of a hygiene intervention on virus spread in an office building.

Viral illnesses have a significant direct and indirect impact on the workplace that burdens employers with increased healthcare costs, low productivity, and absenteeism. Workers' direct contact with each other and contaminated surfaces contributes to the spread of viruses at work. This study quantifies the impact of an office wellness intervention (OWI) to reduce viral load in the workplace. The OWI includes the use of a spray disinfectant on high-touch surfaces and providing workers with alcohol-based hand sanitizer gel and hand sanitizing wipes along with user instructions. Viral transmission was monitored by applying an MS2 phage tracer to a door handle and the hand of a single volunteer participant. At the same time, a placebo inoculum was applied to the hands of four additional volunteers. The purpose was to evaluate the concentration of viruses on workers' hands and office surfaces before and after the OWI. Results showed that the OWI significantly reduced viable phage concentrations per surface area on participants' hands, shared fomites, and personal fomites (p = 0.0001) with an 85.4% average reduction. Reduction of virus concentrations on hands and fomites is expected to subsequently minimize the risk of infections from common enteric and respiratory pathogens. The surfaces identified as most contaminated were the refrigerator, drawer handles and sink faucets in the break room, along with pushbar on the main exit of the building, and the soap dispensers in the women's restroom. A comparison of contamination in different locations within the office showed that the break room and women's restrooms were the sites with the highest tracer counts. Results of this study can be used to inform quantitative microbial risk assessment (QMRA) models aimed at defining the relationship between surface contamination, pathogen exposure and the probability of disease that contributes to high healthcare costs, absenteeism, presenteeism, and loss of productivity in the workplace.

Evaluation of in vitro bioactivity and in vitro biocompatibility of Polycaprolactone/Hyaluronic acid/Multiwalled Carbon Nanotubes/Extract from Mimosa tenuiflora composites.

BACKGROUND: The development of biomaterial scaffolds and implementation of tissue engineering techniques are necessary. Therefore, Polycaprolactone/Sodium Hyaluronate/Multiwalled Carbon Nanotubes/Extract of Mimosa tenuiflora composites have been produced by a thermally-induced phase separation method. OBJECTIVE: The objective of this research was to evaluate the in vitro bioactivity and in vitro biocompatibility of the composites. METHODS: The in vitro bioactivity of the composites was assessed by soaking them in simulated body fluid for 7, 14, 21, and 28 days. The structure and composition of the composites were analyzed using scanning electron microscopy coupled with energy dispersive spectroscopy and Fourier transform infrared spectroscopy. Also, the in vitro biocompatibility of the composites was evaluated by means of alkaline phosphatase activity of the osteoblasts and by measuring the metabolic activity of the cells using MTT assay. RESULTS: The results show a porous and interconnected morphology with enhanced bioactivity. It was observed that the incorporation of Mimosa tenuiflora in the composites promotes increased viability of osteoblasts in the scaffolds. CONCLUSIONS: The results show the efficiency of bioactive and biocompatible composites and their potential as candidates for tissue engineering applications.

Momento de inicio de radioterapia posoperatoria como factor pronóstico en pacientes con cáncer de laringe avanzado / Time to initiation of postoperative radiotherapy as a prognostic factor in patients with advanced laryngeal cancer

RESUMEN Introducción: Dentro de los factores que juegan un rol en la supervivencia y recidiva de enfermedad de los pacientes con cáncer laríngeo escamoso operados se encuentra el tiempo de inicio de la radioterapia (RT) posoperatoria. Objetivo: Determinar el impacto del retraso de inicio de RT posoperatoria en la supervivencia y recidiva de enfermedad en pacientes con cáncer de laringe escamoso avanzado operado. Material y método: Estudio tipo cohorte retrospectiva. Recolección de datos mediante revisión de fichas clínicas. Análisis de supervivencia y recidiva de enfermedad mediante el método de Kaplan-Meier, comparación de curvas con prueba de Log-Rank y modelo de regresión de Cox para análisis de factores pronósticos. Resultados: El tiempo de espera entre la cirugía y el inicio de la RT en nuestras realidades hospitalarias fueron 11 semanas. La supervivencia específica a 5 años en los pacientes que comienzan la RT ≤6 semanas desde la cirugía es de 33,3% y disminuye a 20% en aquellos que la comienzan >6 semanas (p =0,20). Conclusión: Los pacientes que inician la RT en más de 6 semanas desde la cirugía no presentan una diferencia estadísticamente significativa en el pronóstico.

ABSTRACT Introduction: Among the factors that play a role in the survival and recurrence of disease of patients with operated squamous laryngeal cancer is the time to initiation of postoperative radiotherapy (RT). Aim: To determine the impact of delayed onset of postoperative RT on survival and disease recurrence in patients with advanced operated squamous laryngeal cancer. Material and Method: Retrospective cohort study. Collection of data through review of clinical records. Analysis of survival and disease recurrence using the Kaplan-Meier method, comparison of curves with Log-Rank test and Cox regression model for analysis of prognostic factors. Results: The waiting time between surgery and the initiation of RT in our hospital realities was 11 weeks. The 5-year specific survival in patients who start RT ≤ 6 weeks after surgery is 33.3% and decreases to 20% in those who start > 6 weeks (p = 0.20). Conclusion: Patients who start RT in more than 6 weeks after surgery do not present a statistically significant difference in prognosis.

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments.

Pathogens that infect the gastrointestinal and respiratory tracts are subjected to intense pressure due to the environmental conditions of the surroundings. This pressure has led to the development of mechanisms of bacterial tolerance or persistence which enable microorganisms to survive in these locations. In this review, we analyze the general stress response (RpoS mediated), reactive oxygen species (ROS) tolerance, energy metabolism, drug efflux pumps, SOS response, quorum sensing (QS) bacterial communication, (p)ppGpp signaling, and toxin-antitoxin (TA) systems of pathogens, such as Escherichia coli, Salmonella spp., Vibrio spp., Helicobacter spp., Campylobacter jejuni, Enterococcus spp., Shigella spp., Yersinia spp., and Clostridium difficile, all of which inhabit the gastrointestinal tract. The following respiratory tract pathogens are also considered: Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cenocepacia, and Mycobacterium tuberculosis Knowledge of the molecular mechanisms regulating the bacterial tolerance and persistence phenotypes is essential in the fight against multiresistant pathogens, as it will enable the identification of new targets for developing innovative anti-infective treatments.