A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

\u27\u27This project was a collaboration with labs at the University of Pennsylvania, North Carolina State University, University of Wisconsin at Madison, and Albert Einstein College of Medicine, and featured senior thesis work by Haverford Biology alum Ben Miltenberg \u2717.\u27\u27 -- author-supplied abstract

Avian influenza virus isolated in wild waterfowl in Argentina: Evidence of a potentially unique phylogenetic lineage in South America

Avian influenza (AI) viruses have been sporadically isolated in South America. The most recent reports are from an outbreak in commercial poultry in Chile in 2002 and its putative ancestor from a wild bird in Bolivia in 2001. Extensive surveillance in wild birds was carried out in Argentina during 2006-2007. Using RRT-PCR, 12 AI positive detections were made from cloacal swabs. One of those positive samples yielded an AI virus isolated from a wild kelp gull (Larus dominicanus) captured in the South Atlantic coastline of Argentina. Further characterization by nucleotide sequencing reveals that it belongs to the H13N9 subtype. Phylogenetic analysis of the 8 viral genes suggests that the 6 internal genes are related to the isolates from Chile and Bolivia. The analysis also indicates that a cluster of phylogenetically related AI viruses from South America may have evolved independently, with minimal gene exchange, from influenza viruses in other latitudes. The data produced from our investigations are valuable contributions to the study of AI viruses in South America.Centro de Estudios Parasitológicos y de Vectore

Avian influenza virus isolated in wild waterfowl in Argentina: Evidence of a potentially unique phylogenetic lineage in South America

Avian influenza (AI) viruses have been sporadically isolated in South America. The most recent reports are from an outbreak in commercial poultry in Chile in 2002 and its putative ancestor from a wild bird in Bolivia in 2001. Extensive surveillance in wild birds was carried out in Argentina during 2006-2007. Using RRT-PCR, 12 AI positive detections were made from cloacal swabs. One of those positive samples yielded an AI virus isolated from a wild kelp gull (Larus dominicanus) captured in the South Atlantic coastline of Argentina. Further characterization by nucleotide sequencing reveals that it belongs to the H13N9 subtype. Phylogenetic analysis of the 8 viral genes suggests that the 6 internal genes are related to the isolates from Chile and Bolivia. The analysis also indicates that a cluster of phylogenetically related AI viruses from South America may have evolved independently, with minimal gene exchange, from influenza viruses in other latitudes. The data produced from our investigations are valuable contributions to the study of AI viruses in South America.Centro de Estudios Parasitológicos y de Vectore

A global analysis of the impact of COVID-19 stay-at-home restrictions on crime

The implementation of COVID-19 stay-at-home policies was associated with a considerable drop in urban crime in 27 cities across 23 countries. More stringent restrictions over movement in public space were predictive of larger declines in crime. The stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.Peer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change+/-100) revealed a mean reduction of smell (-79.7+/- 28.7, mean+/- SD), taste (-69.0+/- 32.6), and chemesthetic (-37.3+/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.Additional co-authors: Veronica Pereda-Loth, Shannon B Olsson, Richard C Gerkin, Paloma Rohlfs Domínguez, Javier Albayay, Michael C. Farruggia, Surabhi Bhutani, Alexander W Fjaeldstad, Ritesh Kumar, Anna Menini, Moustafa Bensafi, Mari Sandell, Iordanis Konstantinidis, Antonella Di Pizio, Federica Genovese, Lina Öztürk, Thierry Thomas-Danguin, Johannes Frasnelli, Sanne Boesveldt, Özlem Saatci, Luis R. Saraiva, Cailu Lin, Jérôme Golebiowski, Liang-Dar Hwang, Mehmet Hakan Ozdener, Maria Dolors Guàrdia, Christophe Laudamiel, Marina Ritchie, Jan Havlícek, Denis Pierron, Eugeni Roura, Marta Navarro, Alissa A. Nolden, Juyun Lim, KL Whitcroft, Lauren R. Colquitt, Camille Ferdenzi, Evelyn V. Brindha, Aytug Altundag, Alberto Macchi, Alexia Nunez-Parra, Zara M. Patel, Sébastien Fiorucci, Carl M. Philpott, Barry C. Smith, Johan N Lundström, Carla Mucignat, Jane K. Parker, Mirjam van den Brink, Michael Schmuker, Florian Ph.S Fischmeister, Thomas Heinbockel, Vonnie D.C. Shields, Farhoud Faraji, Enrique Enrique Santamaría, William E.A. Fredborg, Gabriella Morini, Jonas K. Olofsson, Maryam Jalessi, Noam Karni, Anna D'Errico, Rafieh Alizadeh, Robert Pellegrino, Pablo Meyer, Caroline Huart, Ben Chen, Graciela M. Soler, Mohammed K. Alwashahi, Olagunju Abdulrahman, Antje Welge-Lüssen, Pamela Dalton, Jessica Freiherr, Carol H. Yan, Jasper H. B. de Groot, Vera V. Voznessenskaya, Hadar Klein, Jingguo Chen, Masako Okamoto, Elizabeth A. Sell, Preet Bano Singh, Julie Walsh-Messinger, Nicholas S. Archer, Sachiko Koyama, Vincent Deary, Hüseyin Yanik, Samet Albayrak, Lenka Martinec Novákov, Ilja Croijmans, Patricia Portillo Mazal, Shima T. Moein, Eitan Margulis, Coralie Mignot, Sajidxa Mariño, Dejan Georgiev, Pavan K. Kaushik, Bettina Malnic, Hong Wang, Shima Seyed-Allaei, Nur Yoluk, Sara Razzaghi, Jeb M. Justice, Diego Restrepo, Julien W Hsieh, Danielle R. Reed, Thomas Hummel, Steven D Munger, John E Haye

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Effect of polyvinilpyrrolidone, starch and sodium laurylsulphate on the dissolution of acetylsalicilic acid tablets

Se analizó el efecto de un aglutinante (polivinilpirrolidona, PVP), de un disgregrante (almidón) y de un tensioactivo (laurilsulfato de sodio) sobre el proceso de disolución de comprimidos de ácido acetilsalicílico (AAS), calculándose una serie de parámetros a fin de determinar la bioequivalencia in vitro de los mismos. Además se verificó la variación de dichos parámetros luego de un almacenamiento de los comprimidos durante 6 meses, en condiciones de estantería. Los resultados muestran que la presencia del aglutinante (PVP) en la formulación afecta notablemente la liberación del principio activo por lo que el proceso de disolución se ve alterado.La presencia del tensioactivo (LSS) mejora la acción disgregante del almidón aún en aquellas formulaciones que contienen PVP, lo que confwma lo descripto por algunos autores. Las variaciones en el porcentaje del contenido de almidón en los comprimidos comerciales (10 al 20%) exhiben diferencias estadísticamente significativas. El estudio de bioequivalencia entre las formulaciones elaboradas y los comprimidos comerciales indica que no todos los productos analizados son bioequivalentes entre síAn analysis was made of the effect of a binder (polyvinilpyrrolidone, PVP), of a disintegrant (starch), and of a tensioactive (sodium laurylsulphate) on the process of dissolution of acetylsalicylic acid (ASA) tablets, a series of parameters having been reckoned in order to determine their in vitro bioequivalence. Verification was also made of the variation of the aforesaid parameters after a six months on shelves storage of the tablets. The results show that the presence of the binder (PVP) in the formulation affects the liberation of the active principle remarkably, the dissolution process being altered this way. The presence of the tensioactive (SLS) improves the disintegrant action of starch, even in those formulations with PVP, which comfirms some author's opinion. The percentage variations of the starch content in the commercial tablets (10 to 20%) show differences statistically significant. The study of bioequivalence between elaborated formulations and commercial tablets shows that not all the analysed products are reciprocally bioequivalent.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Celullose and vynil polymers in the formulation of hydrophyllic matrix: drug release kinetics and evaluation of the kinetic model

Se evaluó el comportamiento de diferentes polímeros de derivados celulósicos y vinílicos utili- zados en la elaboración de comprimidos de ácido acetilsalicílico (AAS) formulados como matríz hidrofilica. Se realizaron ensayos de disolución (USP XXIII) para comprimidos de AAS de liberación controlada, elaborándose los perfiles de disolución correspondientes. Los datos obtenidos fueron tratados empleando modelos que consideran la liberación del principio activo como procesos cinéticos de orden cero, primer orden y los modelos propuestos por Higuchi (raíz cuadrada del tiempo) y Hixson y Crowell (ley de la raíz cúbica), considerando al factor de determinación () como criterio comparativo. En modelos con alto factor de determinación, donde no puede distinguirse el mecanismo de liberación del principio activo, la bondad del ajuste fué evaluado por la estimación de la suma de cuadrados de los residuales del error; la ecuación con la mínima varianza estimada fue considerada como la que mejor ajusta y la presencia de diferencias estadísticamente significativas con los otros modelos se observó mediante el Test F. La bioequivalencia de las formulaciones se determinó mediante análisis de varianza del porcentaje de eficiencia de disolución (%ED), y mediante el método de Tuckey se estableció entre quienes existen diferencias significativas para un nivel de p<0,05. Se lograron buenos resultados con Carbopol al 60%, lográndose una matríz dura, erosionable con una cinética de pseudo-orden 0; con Carbopol al 10% y al 30%, asociado a Polietilenglicol 4000; con PVP en todas las proporciones (l0%,30% y 60%) con muy escasa influencia del porcentaje del polímero sobre los valores de disolución, verificándose una cinética de liberación de orden 1. En las formulaciones elaboradas con HPMC al 30% y al 60%, los comprimidos se disgregan inmediatamente al ser introducidos en el medio de disolución, por lo que no actúan como una forma farmacéutica de liberación controlada, pero al final de la experiencia se observa, por efecto de la agitación, la formación de un flóculo gelatinoso, transparente; por ello al analizar el mecanismo por el cual se libera el principio activo, se determinó que en ambas formulaciones la liberación del fármaco es dependiente de la velocidad de difusión del mismo a través del polímero (raíz cuadrada del tiempo.The behavior of differeiit polymers of celullose and vinyl derivatives, used in the elaboration of acetylsalicilic acid (ASA) tablets formulated as hydrophyllic matrix, was evaluated. Dissolution trials (USP XXIII) for controlled release ASA tablets were carried out, being elaborated the corresponding dissolution profiles. The obtained data were treated ernploying models that consider the release of the active principle as kinetic proceses of zero-order, first-order and the models proposed by Higuclh (square root time) and Hixson and Crowell (law of the cube root), considering to the correlation factor as comparative approach. In models with high correlation factor, where it cannot be distinguislied the release mechanism of the active principle, the kindness of the fitting was evaluated by estimating the residual sum of squares of the deviations; the equation with the least variance estimate was considered to be the best fit and its statistical significance with the other models was shown by the F Test. The bioequivalence of the formulations was determined by means of variance analysis of the percentage of dissoluyion efficiency (%ED), and by the Tuckey's method was established between who exist meaningful differences for a leve1 of p<0.05. Good results were acheved with Carbopol to 60% being obtained a hard , erosionable matrix with a kinetics of zero pseudo-order; with Carbopol to 10% and to 30%. associated to Polietilenglicol 4000; with PVP in all the proportions (10%. 30% and 60%) with very scarce influence of the percentage of the polymer on the dissolution values. being verified a kinetics of first-order release. In the formulations elaborated with HPMC to 30% and 60%, the tablets disintegrated immediately after being introduced in the medium of dissolution, and therefore they do not act as a pharmaceutical form of controlled release; but at the end of the experience, for effect of the agitation, the formation of a jellied, transparent flocculo was observed; hereat. when analyzing the mechanism for which the active principle is released, it was determined that in both formulations the release of the drug is dependent of its diffusion speed through the polymer (square root of the time).Trabajo presentado en el VII Congreso Argentino del Medicamento (Mar del Plata, 1998)Colegio de Farmacéuticos de la Provincia de Buenos Aire