Stroke care and collaborative academic research in Latin America.

OBJECTIVE: A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). MATERIALS AND METHODS: A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. RESULTS: The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage-ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. CONCLUSIONS: Regional networks foster the conduct of multicenter studies -particularly randomized controlled trials-, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.

Impact of COVID-19 Pandemic on Stroke Severity and Mortality in the South-East of Santiago, Chile.

Background and purpose; Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behaviour of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile. METHODS: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile. RESULTS: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003). CONCLUSION: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.

Registro de coloración anormal del oso hormiguero norteño Tamandua mexicana (Saussure, 1860) y notas sobre su límite sur de distribución / Abnormal coloration record of the northern tamandua Tamandua mexicana (saussure, 1860) and notes on its southernmost distribution

Resumen Presentamos el registro de un individuo de oso hormiguero norteño (Tamandua mexicana) con color de pelaje anormalmente blanco. Este individuo fue fotografiado con una cámara trampa en el bosque seco ecuatorial en el departamento de Lambayeque, a 560 m de altitud, en del noroeste del Perú. No pudimos diferenciar si la causa de esta aberración cromática correspondió a un caso de albinismo o de leucismo, sin embargo, destacamos este primer registro excepcional para la especie en Perú. Adicionalmente, hacemos una revisión de su presencia en el extremo sur de su distribución global.

Abstract We present the record of an individual of northern tamandua (Tamandua mexicana) with abnormal white coloration that was photographed with a camera trap in the equatorial dry forest in the department of Lambayeque, at elevation of 560 m, northwest Peru. We could not determine if this chromatic aberration was a case of leucism or albinism, but we highlight this uncommon record as the first for Peru. We also revised the information about its presence in the southern portion of its global range.

Studies of protein oxidation as a product quality attribute on a scale-down model for cell culture process development.

UNLABELLED: Of importance to the biological properties of proteins produced in cell culture systems are the complex post-translational modifications that are affected by variations in process conditions. Protein oxidation, oxidative modification to intracellular proteins that involves cleavage of the polypeptide chain, and modifications of the amino acid side chains can be affected by such process variations. Dissolved oxygen is a parameter of increasing interest since studies have shown that despite the necessity of oxygen for respiration, there may also be some detrimental effects of oxygen to the cell. Production and accumulation of reactive oxygen species can cause damage to proteins as a result of oxidation of the cell and cellular components. Variation, or changes to cell culture products, can affect function, clearance rate, immunogenicity, and specific activity, which translates into clinical implications. The effect of increasing dissolved oxygen on protein oxidation in immunoglobulin G3-producing mouse hybridoma cells was studied using 50 mL high-throughput mini-bioreactors that employ non-invasive optical sensor technology for monitoring and closed feedback control of pH and dissolved oxygen. Relative protein carbonyl concentration of proteins produced under varying levels of dissolved oxygen was measured by enzyme-linked immunosorbent assay and used as an indicator of oxidative damage. A trend of increasing protein carbonyl content in response to increasing dissolved oxygen levels under controlled conditions was observed. LAY ABSTRACT: Protein oxidation, oxidative modification to intracellular proteins that involves cleavage of the polypeptide chain, and modifications of the amino acid side chains can be affected by variations in dissolved oxygen levels in cell culture systems. Studies have shown that despite the necessity of oxygen for respiration, there may be detrimental effects of oxygen to the cell. Production and accumulation of reactive oxygen species can cause damage to proteins as a result of oxidation of the cell and cellular components, affecting function, clearance rate, immunogenicity, and specific activity, which translates into clinical implications. The effect of increasing dissolved oxygen on protein oxidation in immunoglobulin G3-producing mouse hybridoma cells was studied using 50 mL high-throughput mini-bioreactors that employ non-invasive optical sensor technology for monitoring and closed feedback control of pH and dissolved oxygen. Protein carbonyl concentration of proteins produced under varying levels of dissolved oxygen was measured by enzyme-linked immunosorbent assay and used as an indicator of oxidative damage. A trend of increasing protein carbonyl content in response to increasing dissolved oxygen levels under controlled conditions was observed.

A case study in converting disposable process scouting devices into disposable bioreactors as a future bioprocessing tool.

In this study, we perform mass transfer characterization (k(L) a) on a novel mechanically driven/stirred Process Scouting Device, PSD, (SuperSpinner D 1000®, SSD) and demonstrate that this novel device can be viewed as disposable bioreactor. Using patch-based optical sensors, we were able to monitor critical cell culture environmental conditions such as dissolved oxygen (DO) and pH in SSD for comparison to a 1 L standard spinner (SS) flask. We also coupled these mass transfer studies with mixing time studies where we observed relative high mixing times (5.2 min) that are typically observed in production scale bioreactors. Decreasing the mixing time 3.5-fold resulted in 30% increase in k(L) a (from 2.3 to 3.0 h(-1) ) and minimum DO level increased from 0% to 20% for our model hybridoma cell line. Finally, maximum viable cell density and protein titer stayed within ±20% of historical data, from our standard 5 L stirred bioreactor (Biostat®) operated under active DO control.

Optical sensor enabled rocking T-flasks as novel upstream bioprocessing tools.

During the past decade, novel disposable cell culture vessels (generally referred to as Process Scouting Devices or PSDs) have become increasingly popular for laboratory scale studies and seed culture generation. However, the lack of engineering characterization and online monitoring tools for PSDs makes it difficult to elucidate their oxygen transfer capabilities. In this study, a mass transfer characterization (k(L)a) of sensor enabled static and rocking T-flasks is presented and compared with other non-instrumented PSDs such as CultiFlask 50®, spinner flasks, and SuperSpinner D 1000®. We have also developed a mass transfer empirical correlation that accounts for the contribution of convection and diffusion to the volumetric mass transfer coefficient (k(L)a) in rocking T-flasks. We also carried out a scale-down study at matched k(L) a between a rocking T75-flask and a 10 L (2 L filling volume) wave bioreactor (Cultibag®) and we observed similar DO and pH profiles as well as maximum cell density and protein titer. However, in this scale-down study, we also observed a negative correlation between cell growth and protein productivity between the rocking T-flask and the wave bioreactor. We hypothesize that this negative correlation can be due to hydrodynamic stress difference between the rocking T-flask and the Cultibag. As both cell culture devices share key similarities such as type of agitation (i.e., rocking), oxygen transfer capabilities (i.e., k(L)a) and disposability, we argue that rocking T-flasks can be readily integrated with wave bioreactors, making the transition from research-scale to manufacturing-scale a seamless process.

Prognosis of cryptogenic ischemic stroke: a prospective single-center study in Chile.

Approximately 25%-40% of ischemic strokes are considered of unknown cause (ie, cryptogenic). The available information on associated risk factors, functional outcome, and recurrence of this subtype of stroke is limited, especially for the Chilean population. We conducted a prospective cohort study of 380 patients aged ≥ 18 years admitted consecutively to a stroke unit with demonstrated ischemic stroke. The stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The modified Rankin Scale score and Barthel Index were used to assess functional outcome. The Kaplan-Meier product-limit method and Cox proportional hazards regression analysis were used to identify predictors of recurrent stroke during the follow-up period (mean, 2.1 years). Cryptogenic stroke (CS) was diagnosed in 76 patients (20%), 55.2% of them male, with a mean age of 62 ± 17 years. CS was the third most common stroke subtype after the large-artery disease (29%) and cardioembolic (24.4%) subtypes. After adjustment for age and sex, no vascular risk factors or laboratory parameters assessed at the time of admission were found to be predictive of CS. The CS subtype had the lowest rate of stroke recurrence at the end of the follow-up period (n = 4; 2.5% per year; odds ratio, 0.32; 95% confidence interval, 0.11-0.91; P = .022), a favorable functional outcome (mean modified Rankin Scale score, 2; mean Barthel Index, 77), and no increase in mortality risk (odds ratio, 0.73; 95% confidence interval, 0.29-1.77; P = .48). Our findings demonstrate that patients with no definite etiology identified after an extensive workup are at lower risk of recurrence and more likely to have a favorable outcome. No risk factors distinguish CS from other stroke subtypes in our study population.

Integrating a 250 mL-spinner flask with other stirred bench-scale cell culture devices: a mass transfer perspective.

The bioprocess development cycle is a complex task that requires a complete understanding of the engineering of the process (e.g., mass transfer, mixing, CO(2) removal, process monitoring, and control) and its affect on cell biology and product quality. Despite their widespread use in bioprocess development, spinner flasks generally lack engineering characterization of critical physical parameters such as k(L)a, P/V, or mixing time. In this study, mass transfer characterization of a 250-mL spinner flask using optical patch-based sensors is presented. The results quantitatively show the effect of the impeller type, liquid filling volume, and agitation speed on the volumetric mass transfer coefficient (k(L)a) in a 250-mL spinner flask, and how they can be manipulated to match mass transfer capability at large culture devices. Thus, process understanding in spinner flasks can be improved, and these devices can be seamlessly integrated in a rational scale-up strategy from cell thawing to bench-scale bioreactors (and beyond) in biomanufacturing.

Ischemic stroke as the first manifestation of severe ventricular hypertrabeculation/non-compaction.

A rare congenital myocardial defect, known as left ventricular hypertrabeculation/non-compaction (LVHT), has been occasionally described associated with thrombus formation with a potential systemic embolic risk, but its association with ischemic strokes remains controversial. We report a case of ischemic stroke in a patient with severe LVHT and ventricular dysfunction as a possible etiologic synergistic association. In absence of other embolic sources, a severe LVTH associated with ventricular dysfunction could constitute a potential source of brain embolism, especially in patients with high suspicion of an embolic mechanism of ischemic stroke.

Derrame isquêmico como a primeira manifestação de hipertrabeculação/não-compactação ventricular grave / Ischemic stroke as the first manifestation of severe ventricular hypertrabeculation/non-compaction

Um raro defeito congênito do miocárdio, conhecido como hipertrabeculação/não-compactação do ventrículo esquerdo (HTVE/NCVE) tem sido ocasionalmente descrito em associação com a formação de trombos com um potencial risco embólico sistêmico, mas sua associação com derrames isquêmicos permanece controversa. Reportamos o caso de um derrame isquêmico em paciente com grave (HTVE/NCVE) e disfunção ventricular como uma possível associação sinérgica etiológica. Na ausência de outras fontes embólicas, uma grave HTVE/NCVE associada com disfunção ventricular poderia constituir uma fonte potencial de embolismo cerebral, especialmente em pacientes com alta suspeita de um mecanismo embólico de derrame sistêmico.

A rare congenital myocardial defect, known as left ventricular hypertrabeculation/non-compaction (LVHT), has been occasionally described associated with thrombus formation with a potential systemic embolic risk, but its association with ischemic strokes remains controversial. We report a case of ischemic stroke in a patient with severe LVHT and ventricular dysfunction as a possible etiologic synergistic association. In absence of other embolic sources, a severe LVTH associated with ventricular dysfunction could constitute a potential source of brain embolism, especially in patients with high suspicion of an embolic mechanism of ischemic stroke.

Dissolved oxygen and pH profile evolution after cryovial thaw and repeated cell passaging in a T-75 flask.

Routine cell culture is done in small-scale disposable vessels (typically 0.1-100 mL volumes) in academia and industry. Despite their wide use in bioprocess development (i.e., process optimization and process validation), miniature process scouting devices (PSDs) are considered "black boxes" because they are generally not equipped with sensors. In this study, we show that on-line monitoring of dissolved oxygen (DO) and pH in a T-75 flask-based PSD can be achieved during cell passaging and that this information can be linked to different cellular metabolic states. In this case, on-line monitoring of DO and pH show three distinctive metabolic regions in passages 1-18, 19-28, 29-54 and in particular, the shift in the pH curve, the specific oxygen uptake rate (q(O2)), and the lactate production rate to the oxygen consumption rate yield (Y(Lac/ox)) confirm the existence of these distinctive metabolic regions. These findings are particularly useful because they show that sensor equipped PSDs can help to monitor cell culture behavior after thaw, in pre- and seed culture prior to scale-up and in development/optimization studies. Such routine monitoring will help to develop more consistent cell culture techniques.

Optical analysis of liquid mixing in a minibioreactor.

A novel optical sensor was used to study mixing and mean circulation time in a model minibioreactor (12.5 mL stirred vessel, equipped with a paddle impeller). Rotational rates in the range of 10-1,000 rpm corresponding to Reynolds number between 14 and 1,350 were studied. Results suggest that depending on the impeller rotational speed, mixing times up to 214 +/- 87 s can be reproducibly achieved. The minibioreactor was operated in the transitional regime, and it was determined that the non-dimensional form for mixing time, NTheta(M) was linearly dependent on Reynolds number. A linear correlation between mean circulation time and the inverse of rotational speed was also determined. The mean circulation time dependence on rotational speed in the 12.5 mL stirred vessel is similar to those found in large-scale stirred vessels. These results suggest that mixing and circulation times found in large-scale reactors can be replicated in minibioreactors.

Confocal optical system: a novel noninvasive sensor to study mixing.

A novel confocal optical system to study mixing time in small-scale bioreactors is presented. The system is designed to monitor fluorescence upon tracer addition from a localized confocal volume of 0.21 mL within a glass vessel. The key elements of the fluorescence-based confocal system are a pinhole, a lens, an APD (Avalanche photodiode) detector, and light filters. The optical technique was validated by comparison with a pH-based technique. Finally, the optical sensor was tested and a real cultivation media (i.e., spent mammalian cell media) was used to measure mixing time in a 12.5-mL stirred transparent vessel. High accuracy, easy results interpretation, and low costs are the three most attractive characteristics of the sensor. Because of its noninvasive nature and versatility, the results suggest that the confocal system is a promising tool to perform mixing time studies in stirred vessels.

Revision de la endoprotesis total y parcial de cadera / Total and partial a review of hip endoprotesis

Se analizan nueve cirugias de revision de endoprotesis total y parcial de caderas, efectuadas en pacientes de ambos sexos cuyas edades estaban comprendidas entre los 64 y 76 años de vida durante el periodo de tiempo comprendido entre los años 1994, 1995 y 1996. Se menciona que pese a las dificultades tecnicas que implica el tratamiento en cuestion, el resultado fue bueno en ocho pacientes y regular en el restante