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Abstract The increased availability of remote sensing products and new legislative agendas are driving a growing focus on farm‐level traceability and monitoring to tackle commodity‐driven deforestation. Here, we use data on land use change in Brazil (1985–2021) from Mapbiomas to demonstrate how analyses of the drivers of deforestation are sensitive to the scale of analysis: while pixel‐ or property‐level analyses identify proximate drivers of deforestation, analyses at larger scales (subnational regions or countries) capture more complex land use dynamics, including indirect land use change. We argue that initiatives which seek to monitor and address commodity‐driven deforestation—such as the European Union's deforestation due‐diligence regulation and the World Business Council on Sustainable Development's Greenhouse Gas Protocol—must be conscient of these wider land use dynamics. Only by measuring progress and defining success at multiple scales can initiatives for sustainable commodity sourcing create the right mix of incentives for addressing deforestation.

Objective: To compare the agreement between patient and clinician perceptions of care-related financial issues. Patients and Methods: We surveyed patient-clinician dyads immediately after an outpatient medical encounter between September 2019 and May 2021. They were asked to separately rate (1-10) patient’s level of difficulty in paying medical bills and the importance of discussing cost issues with that patient during clinical encounters. We calculated agreement between patient-clinician ratings using the intraclass correlation coefficient and used random effects regression models to identify patient predictors of paired score differences in difficulty and importance of ratings. Results: 58 pairs of patients (n=58) and clinicians (n=40) completed the survey. Patient-clinician agreement was poor for both measures, but higher for difficulty in paying medical bills (intraclass correlation coefficient=0.375; 95% CI, 0.13-0.57) than for the importance of discussing cost (−0.051; 95% CI, −0.31 to 0.21). Agreement on difficulty in paying medical bills was not lower in encounters with conversations about the cost of care. In adjusted models, poor patient-clinician agreement on difficulty in paying medical bills was associated with lower patient socioeconomic status and education level, whereas poor agreement on patient-perceived importance of discussing cost was significant for patients who were White, married, reported 1 or more long-term conditions, and had higher education and income levels. Conclusion: Even in encounters where cost conversations occurred, there was poor patient-clinician agreement on ratings of the patient’s difficulty in paying medical bills and perceived importance of discussing cost issues. Clinicians need more training and support in detecting the level of financial burden and tailoring cost conversations to the needs of individual patients.

Introduction: The coronavirus 19 disease (COVID-19) increased mortality in organ solid transplant patients due to chronic immunosuppression and significant comorbidity burden. We aim to evaluate patient and graft survival in kidney transplant (KT) recipients who were hospitalized or treated in Intensive Care Units (ICU) after contracting COVID-19. Methods: A retrospective analysis was conducted on adult KT recipients diagnosed with COVID-19 between June 1 and July 31, 2021. The study reported demographics, symptoms, laboratory parameters, and clinical outcomes 30 days after a positive test. Risk factors for mortality were identified through comparisons between hospitalization-in-wards and ICU groups. The Kaplan-Meier method was used to calculate graft and patient survival. Results: 55 KT patients were analysed, recipient age and history of diabetes showed significant differences between groups (p = 0.0124 and p = 0.0506, respectively). Multivariate analysis revealed that diabetes (p = 0.002) and dialysis requirement (p = 0.0006) were significantly associated with mortality risk. The overall mortality rate was 25.5%, with graft loss at 12.7%. Patient survival after 30 days was 74.5%, with significantly higher survival in the hospitalization-in-wards group (p = 0.0001) compared to the ICU group. Conclusions: KT patients diagnosed with COVID-19 are at higher mortality risk than the general population. Our study found that patients in the ICU group experienced worse clinical outcomes and higher mortality rates compared to those in the hospitalization-in-wards group. These findings underscore the importance of closely monitoring COVID-19-implicated KT patients and tailoring treatment plans to minimize risk and improve outcomes.

Abstract Background In people and dogs, torasemide has higher bioavailability, longer half‐life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited. Objective To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin‐angiotensin‐aldosterone system (RAAS). Animals Six clinically healthy adult European shorthair cats. Methods Randomized 4‐period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model. Results Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half‐life was 12.9 hours. Urine output significantly increased after torasemide administration (P

BackgroundThe global COVID-19 pandemic has had a devastating effect on global health, resulting in a strain on healthcare services worldwide. The faster a patient with acute ischemic stroke (AIS) receives reperfusion treatment, the greater the odds of a good functional outcome. To maintain the time-dependent processes in acute stroke care, strategies to reorganize infrastructure and optimize human and medical resources were needed.MethodsData from AIS patients who received thrombolytic therapy were prospectively assessed in the emergency department (ED) of Hospital de Clínicas de Porto Alegre from 2019 to 2021. Treatment times for each stage were measured, and the reasons for a delay in receiving thrombolytic therapy were evaluated.ResultsA total of 256 patients received thrombolytic therapy during this period. Patients who arrived by the emergency medical service (EMS) had a lower median door-to-needle time (DNT). In the multivariable analysis, the independent predictors of DNT >60 min were previous atrial fibrillation (OR 7) and receiving thrombolysis in the ED (OR 9). The majority of patients had more than one reason for treatment delay. The main reasons were as follows: delay in starting the CT scan, delay in the decision-making process after the CT scan, and delay in reducing blood pressure. Several actions were implemented during the study period. The most important factor that contributed to a decrease in DNT was starting the bolus and continuous infusion of tPA on the CT scan table (decreased the median DNT from 74 to 52, DNT ≤ 60 min in 67% of patients treated at radiology service vs. 24% of patients treated in the ED). The DNT decreased from 78 min to 66 min in 2020 and 57 min in 2021 (p = 0.01).ConclusionAcute stroke care continued to be a priority despite the COVID-19 pandemic. The implementation of a thrombolytic bolus and the start of continuous infusion on the CT scan table was the main factor that contributed to the reduction of DNT. Continuous monitoring of service times is essential for improving the quality of the stroke center and achieving better functional outcomes for patients.

Introduction: The first COVID-19 wave in Ecuador started in March 2020 and extended until November. Several types of drugs have been proposed as a potential treatment during this period, and some affected people have self-medicated.Method: A retrospective study was conducted with 10,175 individuals who underwent RT-PCR tests for SARS-CoV-2 from July to November 2020. We compared the number of positive and negative cases in Ecuador with symptoms and drug consumption. The Chi-square test of independence compared clinical and demographic data and PCR test results. Odds ratios analyzed drug consumption dynamics.Results: Of 10,175 cases, 570 were positive for COVID-19, while 9,605 were negative. In positive cases, there was no association between the RT-PCR result and sex, age, or comorbidities. When considering demographic data, Cotopaxi and Napo had the highest rates of positive cases (25.7% and 18.8%, respectively). Manabí, Santa Elena, and Guayas regions had fewer than 10% positive cases. The Drug consumption dynamic analysis showed that negative COVID-19 cases presented higher drug consumption than positive cases. In both groups, the most consumed medication was acetaminophen. Acetaminophen and Antihistamines had higher odds of consumption in positive PCR cases than in negative. Symptoms like fever and cough were more related to positive RT-PCR results.Conclusion: The first COVID-19 wave in Ecuador has affected the provinces differently. At a national level, the consumption of drugs has been highly associated with self-medication.

Introduction: Vascular access (VA) remains a major source of morbidity for hemodialysis patients (HD). Few data sources adequately capture longitudinal patency of the VA. This study aimed to evaluate VA failure and its related factors in HD patients. Methods: A retrospective cohort study of 985 incident hemodialysis patients treated in clinics of BRCS in Colombia, from January 1rst ,2016, until December 3 of the same year, was done. The cohort's enrollment was on day 1 of HD, and with follow-up for up to 15 months. Association among a group of independent variables and time to failure of the VA was performed, and adjusted by baseline variables using a Cox regression model. Results: A total of 985 patients were included in the study, requiring 1774 procedures of vascular access during follow-up. The mean age was 61 ± 15.6 years. At day 1, 15% were dialyzing with an arteriovenous fistula (AVF) or AVG; and at day 90, this proportion had increased to 70%. The rate of vascular access procedure was 1.95 per patients-year, 95% CI 1.86-2.04. The rate of vascular access failure was 0.66 per patients-year, 95% CI 0.61–0.72. Risk factors for failure in AVF/AVG were age > 65 (p= 0.008), diabetes (p= 0.019), female sex (p= 0.002) rural housing (p

Background. The accuracy of the measurement of renal function in potential living kidney donors (PLKD) is essential. The direct measurement of glomerular filtration rate (mGFR) has been considered the “gold standard.” The estimated GFR (eGFR) with 24-hour urinary creatinine clearance (CrCl) is frequently used because of its availability. We aim to evaluate the correlation and agreement of eGFR using serum-based creatinine formulas (Cockcroft–Gault, MDRD, and CKD-EPI) and the eGFR based on 24-hour urinary CrCl to evaluate kidney function in PLKD. Methods. We evaluated the kidney function in 799 PLKD using 24-hour urinary CrCl method and compared the correlation and agreement with the eGFR based on creatinine formulas (Cockcroft–Gault, MDRD, and CKD-EPI). We calculated the mean bias (difference), precision (SD of this difference), accuracy, and performed Bland–Altman plots. Results. A total of 799 PLKD were analyzed. The age of the PLKD ranged from 18 to 73 years. Weak to mild correlation was observed between 24-hour urinary CrCl and all formulas (ranged from 0.31 to 0.49). The three equations underestimated the GFR. Using the Bland–Altman graphic, we observed that the CKD-EPI was the least scattered and most precise; however, mean bias and the interval range (limits of agreement) of all formulas were too big to assume equivalence between 24-hour urinary CrCl method and eGFR based on creatinine. Results of mean bias were similar when comparing the three equations in patients with CrCl GFR

Contexto: el rechazo crónico mediado por anticuerpos (cABMR, chronic antibody-mediated rejection) se considera una de las principales causas de disfunción crónica del injerto. Objetivo: profundizar en la comprensión de los mecanismos que la ocasionan para diseñar tratamientos efectivos, dado que es muy poco lo que se ha avanzado en el tratamiento de esta patología. Metodología: en esta revisión narrativa de la literatura, presentamos los factores de riesgo relacionados con la disfunción crónica del injerto, haciendo énfasis en la fisiopatología, el diagnóstico y el tratamiento del cABMR. Resultados: el factor de riesgo más relevante para el desarrollo de disfunción crónica del injerto es el desarrollo de anticuerpos donante específicos (DSA) y ABMR. Para el diagnóstico de cABMR activo, se requieren los criterios de Banff 2017 (los tres deben estar presentes: Evidencia histológica de lesión tisular crónica, evidencia de inflamación actual en el endotelio vascular ocasionada por anticuerpos y evidencia serológica de DSA. El cABMR no tiene un tratamiento efectivo. Conclusiones: dado que cABMR no tiene un tratamiento efectivo, es importante disminuir la exposición a los factores de riesgo y hacer un diagnóstico y un tratamiento oportuno de los eventos agudos de lesión renal que contribuyen a la progresión de disfunción crónica del injerto.

Introducción: el síndrome de intolerancia es un proceso inflamatorio que ocurre hasta en un tercio de los pacientes con pérdida del injerto. Cuando no se obtiene una mejoría de los síntomas con el manejo médico, se indica la realización de nefrectomía del riñón trasplantado, sin embargo, este es un procedimiento invasivo que puede estar asociado a mayor morbilidad y mortalidad. Dada la fragilidad de estos pacientes, se plantea la embolización transcatéter del injerto como una alternativa válida y menos invasiva para el tratamiento de este síndrome. Objetivo: describir el uso de la embolización transcatéter como tratamiento al síndrome de intolerancia del injerto. Presentación del caso: se reportan tres casos clínicos de pacientes con sintomatología de entre 15 y 20 días de evolución, consistentes en dolor y tumefacción sobre riñón trasplantado y otros signos y síntomas reportados fueron fiebre, hiporexia, pérdida de peso y hematuria macroscópica. Se describe la evolución de los síntomas que en ninguno de los casos expuestos tuvieron mejoría con el ajuste inmunosupresor, descartando en todos los casos etiología infecciosa y estableciéndose así la sospecha síndrome de intolerancia del injerto. Los pacientes fueron manejados con embolización transcatéter de la arteria del riñón trasplantado y el éxito del tratamiento se definió por la resolución de los síntomas. Discusión y conclusión: entre las primeras 24-48 horas posprocedimiento, los pacientes presentaron una evolución satisfactoria y, finalmente, egreso. La embolización transcatéter del injerto es una alternativa segura a la nefrectomía del trasplante y que es menos invasiva para el tratamiento del síndrome de intolerancia del injerto.

IntroductionAcute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil.MethodsPROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units.ResultsWhen compared with the private setting (n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability.ConclusionPatients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk.

PURPOSEMore than 80% of cervical cancer cases and deaths occur in low- and middle-income countries. Here, we analyze a large geographically extensive cross-sectional data set from the Western rural highlands of Guatemala. Our objective is to better characterize weak points in care along the cervical cancer care continuum and investigate sociodemographic and clinical correlates of loss to follow-up.METHODSWe conducted a retrospective review of electronic health records data from July 21, 2015, through December 10, 2020 for a cytology-based screening and cervical cancer treatment program. We used a care cascade analysis to characterize the progression of individuals through screening, confirmatory testing, and treatment. We examined demographic and clinical factors correlated with screening and loss to follow-up using multivariate logistic regression.RESULTSA total of 8,872 individuals were included in the analysis. Five thousand nine hundred thirteen cervical cancer screenings were conducted. 4.1% of all screening tests were abnormal, including 0.61% cervical intraepithelial neoplasia or overt cervical cancer. Care cascade analysis showed that 67% of eligible women accepted screening. Of those requiring confirmatory testing or treatment, 73% completed recommended follow-up. In adjusted multivariable analysis, prior history of sexual transmitted infection, prior experience with cervical cancer screening, older age, and current contraceptive use were associated with accepting screening. Age and contraceptive use were also associated with retention in care after a positive first screen.CONCLUSIONIn a large rural Guatemalan retrospective cohort, a care continuum analysis showed that both declining the opportunity to receive cervical cancer screening as well as declining confirmatory testing after a first positive screen were both important weak points along the care continuum. These data support the need for comprehensive and culturally appropriate initiatives to improve screening uptake and retention in care.

Introducción: La pandemia por COVID-19 generó la reestructuración de los servicios de salud en el mundo. La teleconsulta ofrece el acceso a la atención en salud a distancia como estrategia de mitigación a la propagación del virus y como una forma flexible de telemedicina. Objetivo: Describir los resultados de atención en salud por modalidad de teleconsulta en pacientes trasplantados durante la pandemia por COVID-19. Materiales y métodos: Estudio descriptivo de corte transversal que describe la experiencia del uso de la teleconsulta durante la pandemia por COVID-19 en un centro de trasplante de órganos en Colombia. La información fue obtenida mediante la recolección directa de la atención en el mes de abril de 2020 y a través del envío de un cuestionario electrónico estructurado para los pacientes atendidos por teleconsulta. Resultados y discusión: Un total de 1139 pacientes con trasplante renal fueron valorados en la modalidad de teleconsulta. Alrededor de 50% de los pacientes atendidos vivían fuera de áreas metropolitanas (n=564,). Un total de 292 (de 800 contactados) respondieron la encuesta enviada con una media de edad de 48 años. Los pacientes presentaron altos porcentajes de satisfacción con el modelo de teleconsulta (n=278, 94%). Se presentaron 2 casos sospechosos de COVID-19, los cuales fueron negativos al realizar la prueba de PCR-RT. Conclusión: La teleconsulta es una herramienta útil en la mitigación de la emergencia sanitaria, con un alto potencial, que genera mayor acceso y oportunidad de atención en salud, presentando altos índices de aceptación.

IntroductionKidney transplantation is the best therapeutical option for CKD patients. Graft loss risk factors are usually estimated with the cox method. Competing risk analysis could be useful to determine the impact of different events affecting graft survival, the occurrence of an outcome of interest can be precluded by another. We aimed to determine the risk factors for graft loss in the presence of mortality as a competing event.MethodsA retrospective cohort of 1454 kidney transplant recipients who were transplanted between July 1, 2008, to May 31, 2019, in Colombiana de Trasplantes, were analyzed to determine risk factors of graft loss and mortality at 5 years post-transplantation. Kidney and patient survival probabilities were estimated by the competing risk analysis. The Fine and Gray method was used to fit a multivariable model for each outcome. Three variable selection methods were compared, and the bootstrapping technique was used for internal validation as split method for resample. The performance of the final model was assessed calculating the prediction error, brier score, c-index and calibration plot.ResultsGraft loss occurred in 169 patients (11.6%) and death in 137 (9.4%). Cumulative incidence for graft loss and death was 15.8% and 13.8% respectively. In a multivariable analysis, we found that BKV nephropathy, serum creatinine and increased number of renal biopsies were significant risk factors for graft loss. On the other hand, recipient age, acute cellular rejection, CMV disease were risk factors for death, and recipients with living donor had better survival compared to deceased-donor transplant and coronary stent. The c-index were 0.6 and 0.72 for graft loss and death model respectively.ConclusionWe developed two prediction models for graft loss and death 5 years post-transplantation by a unique transplant program in Colombia. Using a competing risk multivariable analysis, we were able to identify 3 significant risk factors for graft loss and 5 significant risk factors for death. This contributes to have a better understanding of risk factors for graft loss in a Latin-American population. The predictive performance of the models was mild.

ObjectivesAnti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ.MethodsWe included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay.ResultsA total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen’s kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, p

Introducción: El trasplante renal es considerado la terapia más efectiva para el tratamiento de la enfermedad renal crónica (ERC). Recientemente, el trasplante renal ha aumentado en los pacientes mayores de 60 años dado que presentan ventajas relevantes reportadas en la literatura mundial como menor riesgo de morir en comparación con pacientes de la misma edad que continúan en diálisis. Objetivo: Evaluar la sobrevida del injerto y del paciente adulto mayor en una cohorte de pacientes trasplantados renales. Materiales y métodos: Analizamos retrospectivamente una cohorte de 193 pacientes mayores de 60 años, quienes recibieron trasplante renal en el periodo comprendido entre 2008 a 2019 en nuestros centros de trasplante. Se analizaron variables sociodemográficas y clínicas para determinar la sobrevida del injerto y del paciente al año, 5 y 10 años post-trasplante mediante el método de Kaplan-Meier. Se realizó un modelo de regresión de Cox para evaluar los potenciales factores de riesgo para pérdida del injerto renal en el primer año post-trasplante. Resultados: La media de edad de los pacientes fue de 64.62 ± 3.82 años. La sobrevida del injerto censurada por muerte fue de 90%, 86% y 75% en los años 1, 5 y 10 post-trasplante y la sobrevida del injerto no censurada fue de 82%, 63% y 43% en los mismos periodos documentados. Las principales causas de mortalidad fueron infecciones y enfermedad cardiovascular. La sobrevida del paciente adulto mayor fue de 89%, 70% y 55% en los años 1, 5 y 10 post-trasplante, respectivamente. Los factores de riesgo asociados a pérdida del injerto renal en el primer año post-trasplante fueron: edad mayor a 70 años (HR 4.2; 95% CI 1.1-15.3), sexo femenino (HR 2.7; 95% CI 1.01-7.3) y no adherencia al tratamiento (HR 8.1; 95% CI 2.1-30.7). Conclusión: Los pacientes adultos mayores trasplantados tuvieron desenlaces adecuados en el trasplante renal. Es importante definir herramientas de evaluación del paciente adulto mayor que sean objetivas en el pre-trasplante donde la edad no sea una barrera de acceso al trasplante renal para esta población.

In the past two decades, the Argo Program has collected, processed, and distributed over two million vertical profiles of temperature and salinity from the upper two kilometers of the global ocean. A similar number of subsurface velocity observations near 1,000 dbar have also been collected. This paper recounts the history of the global Argo Program, from its aspiration arising out of the World Ocean Circulation Experiment, to the development and implementation of its instrumentation and telecommunication systems, and the various technical problems encountered. We describe the Argo data system and its quality control procedures, and the gradual changes in the vertical resolution and spatial coverage of Argo data from 1999 to 2019. The accuracies of the float data have been assessed by comparison with high-quality shipboard measurements, and are concluded to be 0.002°C for temperature, 2.4 dbar for pressure, and 0.01 PSS-78 for salinity, after delayed-mode adjustments. Finally, the challenges faced by the vision of an expanding Argo Program beyond 2020 are discussed.

A new LC method for tizanidine hydrochloride in tablet dosage form using a charged aerosol detector (CAD) is described. The influence of various parameters on chromatographic system was investigated by factorial designs and Derringer's desirability. Chromatographic conditions were: mobile phase constituted of acetonitrile and ammonium acetate buffer 17 mM (60:40; v/v), column oven at 39 °C and flow rate 0.8 mL.min-1 performed in on Acclaim Trinity P1 column UV at 230 nm. Thus, it was possible to validate a simple method to assay the tizanidine and its counter-ion in three formulations (drug reference, generic and manipulated). Method showed specificity when challenged by forced degradation and excipients. Finally, the method was compared with USP monograph method demonstrating equivalence in assay evaluation.

Background: Decompressive hemicraniectomy (DHC) is a life-saving procedure for treatment of large malignant middle cerebral artery (MCA) strokes. Post-stroke epilepsy is an additional burden for these patients, but its incidence and the risk factors for its development have been poorly investigated. Objective: To report the prevalence and risk factors for post-stroke seizures and post-stroke epilepsy after DHC for treatment of large malignant MCA strokes in a cohort of 36 patients. Methods: In a retrospective cohort study of 36 patients we report the timing and incidence of post-stroke epilepsy. We analyzed if age, sex, vascular risk factors, side of ischemia, reperfusion therapy, stroke etiology, extension of stroke, hemorrhagic transformation, ECASS scores, National Institutes of Health Stroke Scale (NIHSS) scores, or modified Rankin scores were risk factors for seizure or epilepsy after DHC for treatment of large MCA strokes. Results: The mean patient follow-up time was 1,086 days (SD = 1,172). Out of 36 patients, 9 (25.0%) died before being discharged. After 1 year, a total of 11 patients (30.6%) had died, but 22 (61.1%) of them had a modified Rankin score ≤4. Thirteen patients (36.1%) developed seizures within the first week after stroke. Seizures occurred in 22 (61.1%) of 36 patients (95% CI = 45.17–77.03%). Out of 34 patients who survived the acute period, 19 (55.9%) developed epilepsy after MCA infarcts and DHC (95% CI = 39.21–72.59%). In this study, no significant differences were observed between the patients who developed seizures or epilepsy and those who remained free of seizures or epilepsy regarding age, sex, side of stroke, presence of the clinical risk factors studied, hemorrhagic transformation, time of craniectomy, and Rankin score after 1 year of stroke. Conclusion: The incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC might be very high. Seizure might occur precociously in patients who are not submitted to anticonvulsant prophylaxis. The large stroke volume and the large cortical ischemic area seem to be the main risk factors for seizure or epilepsy development in this subtype of stroke.

The effects of thrombolysis in seizure and epilepsy after acute ischemic stroke have been poorly explored. In this study, we examine risk factors and consequences of intravenous rt-PA for treatment of acute ischemic stroke. In a retrospective cohort study we evaluate risk factors for seizure and epilepsy after stroke thrombolysis, as well as the impact of seizures and epilepsy in outcome of stroke patients. In our cohort, mean age of patients was 67.2 years old (SD = 13.1) and 79 of them (51.6%) were male and. Initial NIHSS mean score were 10.95 (SD = 6.25). Three months NIHSS mean score was 2.09 (SD = 3.55). Eighty seven (56.9%) patients were mRS of 0–1 after thrombolysis. Hemorrhagic transformation was observed in 22 (14.4%) patients. Twenty-one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation (OR = 3.26; 95% CI = 1.08–9.78; p = 0.035) and with mRS ≥ 2 at 3 months after stroke (OR = 3.51; 95% CI = 1.20–10.32; p = 0.022). Hemorrhagic transformation (OR = 3.55; 95% CI = 1.11–11.34; p = 0.033) and mRS ≥ 2 at 3 months (OR = 5.82; 95% CI = 1.45–23.42; p = 0.013) were variables independently associated with post-stroke epilepsy. In our study, independent risks factors for poor outcome in stroke thrombolysis were age (OR = 1.03; 95% CI = 1.01–1.06; p = 0.011), higher NIHSS (OR = 1.08; 95% CI = 1.03–1.14; p = 0.001), hemorrhagic transformation (OR = 2.33; 95% CI = 1.11–4.76; p = 0.024), seizures (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018) and large cortical area (ASPECTS ≤ 7) (OR = 2.04; 95% CI = 1.04–3.84; p = 0.036). Concluding, in this retrospective cohort study, the neurological impairment after thrombolysis (but not before) and hemorrhagic transformation remained independent risk factors for seizures or post-stroke epilepsy after thrombolysis. Moreover, we observed that seizures emerged as an independent risk factor for poor outcome after thrombolysis therapy in stroke patients (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018).

All tumors accumulate genetic alterations, some of which can give rise to mutated, non-self peptides presented by human leukocyte antigen (HLA) molecules and elicit T-cell responses. These immunogenic mutated peptides, or neoantigens, are foreign in nature and display exquisite tumor specificity. The correlative evidence suggesting they play an important role in the effectiveness of various cancer immunotherapies has triggered the development of vaccines and adoptive T-cell therapies targeting them. However, the systematic identification of personalized neoantigens in cancer patients, a critical requisite for the success of these therapies, remains challenging. A growing amount of evidence supports that only a small fraction of all tumor somatic non-synonymous mutations (NSM) identified represent bona fide neoantigens; mutated peptides that are processed, presented on the cell surface HLA molecules of cancer cells and are capable of triggering immune responses in patients. Here, we provide an overview of the existing strategies to identify candidate neoantigens and to evaluate their immunogenicity, two factors that impact on neoantigen identification. We will focus on their strengths and limitations to allow readers to rationally select and apply the most suitable method for their specific laboratory setting.

A iniciação ao desenvolvimento de programação de computadores sempre foi um desafio para professores e alunos. Por meio de novas tecnologias, pessoas que nunca programaram estão conseguindo desenvolver seus aplicativos. Tecnologias baseadas em linguagens de programação visuais, diferentemente das linguagens de programação textuais, os conhecimentos prévios para desenvolvimento são mínimos. Estas linguagens proporcionam desenvolvimento de aplicativos de maneira simples e rápida, procurando despertar o interesse em programação desde o público infantil, alunos de cursos de exatas, com dificuldades em desenvolver raciocínio lógico, até pessoas que não trabalham na área de informática, mas que pretendem desenvolver seus próprios aplicativos.

Background: The effect of early mobilization after acute stroke is still unclear, although some studies have suggested improvement in outcomes. We conducted a randomized, single-blind, controlled trial seeking to evaluate the feasibility, safety, and benefit of early mobilization for patients with acute ischemic stroke treated in a public teaching hospital in Southern Brazil. This report presents the feasibility and safety findings for the pilot phase of this trial. Methods: The primary outcomes were time to first mobilization, total duration of mobilization, complications during early mobilization, falls within 3 months, mortality within 3 months, and medical complications of immobility. We included adult patients with CT- or MRI-confirmed ischemic stroke within 48 h of symptom onset who were admitted from March to November 2012 to the acute vascular unit or general emergency unit of a large urban emergency department (ED) at the Hospital de Clínicas de Porto Alegre. The severity of the neurological deficit on admission was assessed by the National Institutes of Health Stroke Scale (NIHSS). The NIHSS and modified Rankin Scale (mRS, functional outcome) scores were assessed on day 14 or at discharge as well as at 3 months. Activities of daily living (ADL) were measured with the modified Barthel Index (mBI) at 3 months. Results: Thirty-seven patients (mean age 65 years, mean NIHSS score 11) were randomly allocated to an intervention group (IG) or a control group (CG). The IG received earlier (p = 0.001) and more frequent (p Conclusions: This pilot trial conducted at a public hospital in Brazil suggests that early mobilization after acute ischemic stroke is safe and feasible. Despite some challenges and limitations, early mobilization was successfully implemented, even in the setting of a large, complex ED, and without complications. Patients from the IG were mobilized much earlier than controls receiving the standard care provided in most Brazilian hospitals.

We report here neuroimaging findings of a 41 years-old female with molecular diagnosis of CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). CADASIL, the most common form of hereditary stroke, is characterized by headaches and relapsing strokes. More than 95% of patients present mutations of NOTCH3 gene. MRI, the best neuroimaging modality to investigate CADASIL can show lacunar infarcts and less-well demarcated T2 weighted hyperintensities characteristically located in subcortical white matter. There is no specific treatment for CADASIL. Anti-platelet agents such as aspirin might help to prevent new strokes. Other symptoms, like headache, seizures, or other neuropsychiatric manifestations should be appropriately treated.

OBJECTIVE: The aim of this study was to verify incidence and characteristics of sudden unexpected death in patients (SUDEP) with refractory epilepsy and its relation to previous surgery and lesion localization. METHOD: A cross sectional study was carried out in a cohort of 550 patients with refractory epilepsy followed up by the Epilepsy Surgery Program of the University Hospital of PUCRS, Porto Alegre, Brazil, between January, 1992 and July, 2002. Patients were allocated in two groups (operated and non operated). Seizure type, distribution of interictal spikes and MRI findings were correlated with the SUDEP outcome. RESULTS: The estimated incidence of probable SUDEP amounted to 29:1000 individuals. Probable SUDEP occurred in 1.2% of the 166 patients of the non operated group and in 3.7% of the 384 patients who were operated (OR=3.02, 95% CI 0.69-13.16) (p=0.11). Comparing patients who died to patients alive in the operated group a significant difference was observed concerning the following variables: SUDEP patients had a predominance of generalized seizures (p=0.002), extratemporal lesion on MRI (p

Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan.

A paralisia bulbar progressiva, também denominada doença de Fazio-Londe, caracteriza-se pelo acometimento degenerativo progressivo de nervos cranianos bulbares em crianças. Foi descrita primeiramente por Fazio em 1892 e até a presente data somente 30 casos foram relatados na literatura. Acomete ambos os sexos, assumindo dois padrões clínicos, um de início precoce (idade Progressive bulbar palsy, also called Fazio -Londe disease, is characterized by progressive impairment of cranial nerves in children. It was first reported by Fazio in 1892 and until now only 30 cases have been published in the literature. Both sexes can be affected and clinical course can be divided on early (< 6 years age, predominance of respiratory symptoms) and late course (6-20 years of age, predominance of motor symptoms on superior limbs). We report a 4 years old boy that started with intense stridor and respiratory distress, initially being diagnosed as an acute asthma attack. Clinical signs worsened and 12 months latter he already had impairment of cranial nerves V, VII, VIII, IX and X confirmed by clinical examination and neurophysiological evaluation.

Objetivo: determinar a capacidade do sulfato de magnésio na prevenção da eclâmpsia em um grupo de gestantes com pré-eclâmpsia. Métodos: estudo caso-controle em 489 gestantes com o diagnóstico de hipertensão arterial sistêmica (HAS) internadas no HCPA no período de janeiro de 1990 a janeiro de 1997. Para a aferição dos dados, as gestantes foram divididas em dois grupos: as que fizeram uso de sulfato de magnésio (grupo I) e as que não fizeram uso do sulfato de magnésio (grupo II). Todas as pacientes foram manejadas de acordo com o protocolo do Serviço de Ginecologia e Obstetrícia do HCPA para tratamento de gestantes com HAS. Foram aferidas as seguintes variáveis: idade materna, raça, número de convulsões, número de convulsões em gestantes com uso de sulfato de magnésio, tempo de uso de sulfato de magnésio antes e após o parto, mortalidade materna; necessidade de internação em UTI, necessidade de ventilação assistida, e tempo de internação após o parto. Os dados foram avaliados por meio do pacote estatístico Epi-Info 6.0 com análise multivariada. A principal medida foi o uso de sulfato de magnésio. Resultados: não foram encontradas diferenças significativas entre os grupos de usuárias ou não de sulfato de magnésio quanto à idade materna, idade gestacional ou raça. As gestantes que receberam MgSO4 apresentaram médias de pressões diastólica e sistólica significativamente maiores. O grupo de usuárias de sulfato de magnésio teve maior tempo de internação hospitalar e mais necessidade de internação em UTI. A necessidade de uso de respirador artificial e o índice de morte materna foram semelhantes nos dois grupos. Vinte e duas pacientes das 353 gestantes apresentaram uma ou mais convulsões antes da internação. Seis gestantes (27,3%) apresentaram um ou dois novos episódios de convulsão e nenhuma paciente apresentou três ou mais convulsões após o uso sulfato de MgSO4. Conclusões: os resultados do estudo sugerem que as convulsões eclâmpticas podem ser evitadas pela utilização profilática rotineira do sulfato de magnésio.Deve ser considerada uma medida arriscada e indefensável, sob o ponto de vista ético, a decisão de não-utilização profilática do sulfato de magnésio em pacientes pré-eclâmpticas que estejam em trabalho de parto, ou que apresentem sinais clínicos de iminência de convulsão.Purpose: to determine magnesium sulfate effectiveness to prevent eclamptic seizures in pregnant women diagnosed with preeclampsia. Methods: a case-control study involving 489 pregnant patients admitted to the Hospital de Clínicas de Porto Alegre (HCPA) with the diagnosis of hypertension between January 1990 and January 1997. The patients were divided into two groups: those who received magnesium sulfate (Group I) and those who did not (Group II). All patients were treated according to the hospital's standard protocol for the treatment of hypertensive pregnant women. The following variables were assessed: maternal age, race, number of seizures, number of seizures in patients receiving magnesium sulfate, period of magnesium sulfate administration, before and after delivery, maternal mortality, need of ICU care, need of mechanical ventilation and length of hospital stay after delivery. Data were assessed with Epi-Info 6.0 statistical package, using multivariate analysis. The main outcome measure was magnesium sulfate use. Results: no differences were found between the two groups in terms of maternal age, race or gestational age. Women who received magnesium sulfate had a higher mean systolic and diastolic blood pressure. Women in the intervention group had a longer hospital stay and a greater need of ICU care. Need of mechanical ventilation and maternal mortality were similar in the two groups. Twenty-two out of 353 women had one or more seizures before admission to the hospital. Six women (27.3%) had one or two additional seizures after magnesium sulfate administration. No subjects had three or more seizures after receiving magnesium sulfate. Conclusion: the results show that eclamptic seizures can be prevented by routine prophylactic magnesium sulfate administration.

The objective of this study was to assess the effect of a rooted macrophyte Elodea nuttallii on rhizosphere bacterial communities in Hg contaminated sediments. Specimens of E. nuttallii were exposed to sediments from the Hg contaminated Babeni reservoir (Olt River, Romania) in our microcosm. Plants were allowed to grow for two months until they occupied the entirety of the sediments. Total Hg and MMHg were analysed in sediments where an increased MMHg percentage of the total Hg in pore water of rhizosphere sediments was found. E. nuttallii roots also significantly changed the bacterial community structure in rhizosphere sediments compared to bulk sediments. Deltaproteobacteria dominated the rhizosphere bacterial community where members of Geobacteraceae within the Desulfuromonadales and Desulfobacteraceae were identified. Two bacterial operational taxonomic units (OTUs) which were phylogenetically related to sulfate-reducing bacteria (SRB) became abundant in the rhizosphere. We suggest that these phylotypes could be potentially methylating bacteria and might be responsible for the higher MMHg percentage of the total Hg in rhizosphere sediments. However, SRB were not significantly favoured in rhizosphere sediments as shown by qPCR. Our findings support the hypothesis that rooted macrophytes created a microenvironment favorable for Hg methylation. The presence of E. nuttallii in Hg contaminated sediments should therefore not be overlooked.

PURPOSE Access to health care is a long-standing concern for rural patients; however, administrative measures fail to capture the subjective patient experience of accessing health care. The purpose of this review was to synthesize the qualitative literature on patient and caregiver experiences of accessing health care services for chronic disease management among US residents of rural areas. METHODS We searched Embase, MEDLINE, PsycInfo, CINAHL, and Scopus to identify qualitative studies published during 2010-2019. A thematic synthesis approach was used to analyze findings from included studies. RESULTS A total of 62 studies involving 1,354 unique participants were included. The largest share of studies (24.2%) was focused on the experience of patients with cancer, followed by behavioral health (16.1%), HIV and AIDS (14.5%), and diabetes (12.9%). We identified 4 primary analytic themes of barriers and facilitators associated with the experience of accessing health care services for chronic disease management in rural areas: (1) navigating the rural environment, (2) navigating the health care system, (3) financing chronic disease management, and (4) rural life (ie, common elements of a distinct 'rural' way of thinking and behaving). CONCLUSIONS In this comprehensive review, we found that important cultural, structural, and individual factors influenced the rural patient's experience of health care access and use, including barriers and facilitators posed by geographic and built environments, and distinct rural mores. Our findings can inform policies and programs that both facilitate structural aspects of access and include culturally appropriate interventions. Key words: rural health; health care access; barriers; facilitators; chronic disease management; systematic review; qualitative research; vulnerable populations; public health Ann Fam Med 2022;20:266-272. https://doi.org/10.1370/afm.2798, INTRODUCTION Nearly 1 in 5 people in the United States live in rural areas. (1) Chronic health conditions are both more prevalent and associated with higher rates of disease-attributable mortality [...]

Background: Although many oral and dental injuries are not life threatening per se, some conditions require urgent treatment to avoid unnecessary pain, impaired function and tooth loss. Adequate diagnosis and treatment will have a significant impact on the comfort and long‐term prognosis for the patient avoiding the sequela of untreated orofacial injuries. In almost all cases, the diagnosis of dental pathologies requires general anaesthesia, dental probing and charting, and diagnostic imaging (dental radiography and cone beam CT or conventional CT). Aim of the article: Despite being less common than in other disciplines, oral and dental emergencies do occur and cause severe distress to the patient. This article describes several dental and oral pathologies and the approach to diagnosis so that a treatment plan can be provided to colleagues and owners. [ABSTRACT FROM AUTHOR]