Clinical utility of the INECO Frontal Screening for detecting Mild Cognitive Impairment in Parkinson's disease.

Cognitive deficits in Parkinson's disease typically affect executive functions. Recently, the concept of Mild Cognitive Impairment (MCI) has been related to PD (PD-MCI). PD-MCI is considered a transition phase to Parkinson's disease Dementia. Therefore, it is important to identify PD-MCI in a reliable way. OBJECTIVE: To evaluate the sensitivity and specificity of the INECO Frontal Screening (IFS) in detecting cognitive deficits in PD-MCI. Additionally, we compare the IFS and the Addenbrook Cognitive Examination Revised (ACE-R) between three groups; PD-MCI, MCI, and controls. METHODS: The IFS and ACE-R were administered to 36 patients with PD-MCI, 31 with MCI (amnestic-multidomain subtype) and 92 healthy controls. Sensitivity and specificity were determined using ROC analysis. The groups were compared using one-way analysis of variance. RESULTS: The IFS had adequate accuracy in differentiating patients with PD-MCI from healthy controls (AUC=0.77, sensitivity=0.82, specificity=0.77), and good accuracy in differentiating PD-MCI from MCI patients (AUC=0.80, sensitivity=0.82, specificity=0.61). However the IFS had low accuracy in differentiating MCI patients from healthy controls (AUC=0.47, sensitivity=0.52, specificity=0.41). On the ACE-R, the PD-MCI group had low performance in Fluency and Language. Only patients with PD-MCI had difficulties on the IFS, specifically in inhibitory control and visual working memory. This dysexecutive profile explains the sensitivity and specificity values found in the IFS. CONCLUSION: The present study results suggest that the IFS is a suitable screening tool for exploring cognitive dysfunction in PD-MCI, especially in those patients with a dysexecutive profile.

Os déficits cognitivos na doença de Parkinson geralmente afetam as funções executivas. Recentemente, o conceito de Comprometimento Cognitivo Leve (CCL) tem sido relacionado à DP (DP-CCL). O DP-CCL é considerado uma fase de transição para a doença de Parkinson. Portanto, é importante identificar o DP-CCL de maneira acurada. Objetivo: Avaliar a sensibilidade e especificidade do INECO Frontal Screening (IFS) na detecção de déficits cognitivos na DP-CCL. Além disso, comparamos o IFS e o Addenbrook Cognitive Examination Revised (ACE-R) entre três grupos; DP-CCL, CCL e controles. Métodos: O IFS e o ACE-R foram administrados a 36 pacientes com DP-CCL, 31 com CCL (subtipo amnésico-de múltiplos domínios) e 92 controles saudáveis. A sensibilidade e especificidade foram determinadas usando a análise ROC. Os grupos foram comparados usando uma análise de variância unidirecional. Resultados: O IFS teve precisão adequada para diferenciar pacientes com DP-CCL de controles saudáveis ​​(AUC=0, 77, sensibilidade=0, 82, especificidade=0, 77) e boa precisão para diferenciar DP-CCL de CCL (AUC=0, 80, sensibilidade =0, 82, especificidade=0, 61). No entanto, o IFS teve baixa precisão para diferenciar CCL de controles saudáveis ​​(AUC=0, 47, sensibilidade=0, 52, especificidade=0, 41). No ACE-R, o grupo DP-CCL apresentou baixo desempenho em fluência e linguagem. Somente pacientes com DP-CCL apresentaram dificuldades no IFS, especificamente no controle inibitório e na memória de trabalho visual. Esse perfil disexecutivo explica os valores de sensibilidade e especificidade encontrados no IFS. Conclusão: O presente estudo sugeriu que o IFS é uma ferramenta de triagem adequada para explorar a disfunção cognitiva na DP-CCL, principalmente naqueles pacientes com perfil disexecutivo.

Clinical utility of the INECO Frontal Screening for detecting Mild Cognitive Impairment in Parkinson's disease / Utilidade clínica do rastreio frontal INECO para detectar comprometimento cognitivo leve na doença de Parkinson

ABSTRACT Cognitive deficits in Parkinson's disease typically affect executive functions. Recently, the concept of Mild Cognitive Impairment (MCI) has been related to PD (PD-MCI). PD-MCI is considered a transition phase to Parkinson's disease Dementia. Therefore, it is important to identify PD-MCI in a reliable way. Objective: To evaluate the sensitivity and specificity of the INECO Frontal Screening (IFS) in detecting cognitive deficits in PD-MCI. Additionally, we compare the IFS and the Addenbrook Cognitive Examination Revised (ACE-R) between three groups; PD-MCI, MCI, and controls. Methods: The IFS and ACE-R were administered to 36 patients with PD-MCI, 31 with MCI (amnestic-multidomain subtype) and 92 healthy controls. Sensitivity and specificity were determined using ROC analysis. The groups were compared using one-way analysis of variance. Results: The IFS had adequate accuracy in differentiating patients with PD-MCI from healthy controls (AUC=0.77, sensitivity=0.82, specificity=0.77), and good accuracy in differentiating PD-MCI from MCI patients (AUC=0.80, sensitivity=0.82, specificity=0.61). However the IFS had low accuracy in differentiating MCI patients from healthy controls (AUC=0.47, sensitivity=0.52, specificity=0.41). On the ACE-R, the PD-MCI group had low performance in Fluency and Language. Only patients with PD-MCI had difficulties on the IFS, specifically in inhibitory control and visual working memory. This dysexecutive profile explains the sensitivity and specificity values found in the IFS. Conclusion: The present study results suggest that the IFS is a suitable screening tool for exploring cognitive dysfunction in PD-MCI, especially in those patients with a dysexecutive profile.

RESUMO Os déficits cognitivos na doença de Parkinson geralmente afetam as funções executivas. Recentemente, o conceito de Comprometimento Cognitivo Leve (CCL) tem sido relacionado à DP (DP-CCL). O DP-CCL é considerado uma fase de transição para a doença de Parkinson. Portanto, é importante identificar o DP-CCL de maneira acurada. Objetivo: Avaliar a sensibilidade e especificidade do INECO Frontal Screening (IFS) na detecção de déficits cognitivos na DP-CCL. Além disso, comparamos o IFS e o Addenbrook Cognitive Examination Revised (ACE-R) entre três grupos; DP-CCL, CCL e controles. Métodos: O IFS e o ACE-R foram administrados a 36 pacientes com DP-CCL, 31 com CCL (subtipo amnésico-de múltiplos domínios) e 92 controles saudáveis. A sensibilidade e especificidade foram determinadas usando a análise ROC. Os grupos foram comparados usando uma análise de variância unidirecional. Resultados: O IFS teve precisão adequada para diferenciar pacientes com DP-CCL de controles saudáveis ​​(AUC=0, 77, sensibilidade=0, 82, especificidade=0, 77) e boa precisão para diferenciar DP-CCL de CCL (AUC=0, 80, sensibilidade =0, 82, especificidade=0, 61). No entanto, o IFS teve baixa precisão para diferenciar CCL de controles saudáveis ​​(AUC=0, 47, sensibilidade=0, 52, especificidade=0, 41). No ACE-R, o grupo DP-CCL apresentou baixo desempenho em fluência e linguagem. Somente pacientes com DP-CCL apresentaram dificuldades no IFS, especificamente no controle inibitório e na memória de trabalho visual. Esse perfil disexecutivo explica os valores de sensibilidade e especificidade encontrados no IFS. Conclusão: O presente estudo sugeriu que o IFS é uma ferramenta de triagem adequada para explorar a disfunção cognitiva na DP-CCL, principalmente naqueles pacientes com perfil disexecutivo.

The State of Public Health Lead Policies: Implications for Urban Health Inequities and Recommendations for Health Equity.

Although lead has been removed from paint and gasoline sold in the U.S., lead exposures persist, with communities of color and residents in urban and low-income areas at greatest risk for exposure. The persistence of and inequities in lead exposures raise questions about the scope and implementation of policies that address lead as a public health concern. To understand the multi-level nature of lead policies, this paper and case study reviews lead policies at the national level, for the state of California, and for Santa Ana, CA, a dense urban city in Southern California. Through a community-academic partnership process, this analysis examines lead exposure pathways represented, the level of intervention (e.g., prevention, remediation), and whether policies address health inequities. Results indicate that most national and state policies focus on establishing hazardous lead exposure levels in settings and consumer products, disclosing lead hazards, and remediating lead paint. Several policies focus on mitigating exposures rather than primary prevention. The persistence of lead exposures indicates the need to identify sustainable solutions to prevent lead exposures in the first place. We close with recommendations to reduce lead exposures across the life course, consider multiple lead exposure pathways, and reduce and eliminate health inequities related to lead.

Historical Background of Pancreatic Islet Isolation.

Until the discovery of insulin in the twentieth century, diabetes mellitus was a mortal disease with an unclear origin and physiology. Despite the appearance of the concept in an Egyptian papyrus dated c.1550 BC, and the documentation of its study by ancient Chinese, the term "diabetes" was only coined by the Greek Aretaeus in the second century AD. In Europe, the study of diabetes was largely ignored until the seventeenth century, when the characteristic sweet flavor of diabetic urine was first described. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering, long after the first description of the pancreatic islets by Paul Langerhans in 1869. One of the most significant milestones in the field was the discovery of insulin by Banting and collaborators in 1922, which led to the therapeutic development of insulin administration as a life-saving intervention for type 1 diabetic patients. On the other hand, the isolation of islets was first reported by Bensley in 1911, a critical technical achievement that paved the way for clinical islet transplantation. Here we discuss the history of islet isolation, since the firsts studies of diabetes by ancient civilizations to the birth and parallel evolution of islet isolation and transplantation.

Isolation of Mouse Pancreatic Islets of Langerhans.

The aim of any pancreatic islet isolation is obtaining pure, viable and functional pancreatic islets, either for in vitro or in vivo purposes. The islets of Langerhans are complex microorgans with the important role of regulating glucose homeostasis. Imbalances in glucose homeostasis lead to diabetes, which is defined by the American Diabetes Association as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both" (American Diabetes Association 2011). Currently, the rising demand of human islets is provoking a shortage of this tissue, limiting research and clinical practice on this field. In this scenario, it is essential to investigate and improve islet isolation procedures in animal models, while keeping in mind the anatomical and functional differences between species. This chapter discusses the main aspects of mouse islet isolation research, highlighting the critical factors and shortcomings to take into account for the selection and/or optimization of a mouse islet isolation protocol.

Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation.

Pancreatic islet transplantation is a promising therapy for Type I Diabetes. For many years the method used worldwide for islet purification in both rodent and human islet isolation has been Ficoll-based density gradients, such as Histopaque. However, it is difficult to purify islets in laboratories with staff limitations when large scale isolations are required. We hypothesized that filtration could be a more simple and fast alternative to obtain good quality islets. Four separate islet isolations were performed per method, comparing filtration and Histopaque purification with handpicking as the gold standard method for islet purity. Different parameters of quality were assessed: yield in number of islets per pancreas, purity by dithizone staining, viability by Fluorescein Diacetate/Propidium Iodide vital staining and in vitro functionality assessed by Glucose Stimulated Insulin Secretion. Time efficiency and cost were also analyzed. The overall quality of the islets obtained both by Histopaque and filtration was good. Filtration saved almost 90 % of the time consumed by Histopaque purification, and was also cheaper. However, one-third of the islets were lost. Since human and rodent islets share similar size but different density, filtration appears as a purification method with potential interest in translation to clinic.

The temporal and hierarchical control of transcription factors-induced liver to pancreas transdifferentiation.

Lineage-specific transcription factors (TFs) display instructive roles in directly reprogramming adult cells into alternate developmental fates, in a process known as transdifferentiation. The present study analyses the hypothesis that despite being fast, transdifferentiation does not occur in one step but is rather a consecutive and hierarchical process. Using ectopic expression of Pdx1 in human liver cells, we demonstrate that while glucagon and somatostatin expression initiates within a day, insulin gene expression becomes evident only 2-3 days later. To both increase transdifferentiation efficiency and analyze whether the process indeed display consecutive and hierarchical characteristics, adult human liver cells were treated by three pancreatic transcription factors, Pdx1, Pax4 and Mafa (3pTFs) that control distinct hierarchical stages of pancreatic development in the embryo. Ectopic expression of the 3pTFs in human liver cells, increased the transdifferentiation yield, manifested by 300% increase in the number of insulin positive cells, compared to each of the ectopic factors alone. However, only when the 3pTFs were sequentially supplemented one day apart from each other in a direct hierarchical manner, the transdifferentiated cells displayed increased mature ß-cell-like characteristics. Ectopic expression of Pdx1 followed by Pax4 on the 2(nd) day and concluded by Mafa on the 3(rd) day resulted in increased yield of transdifferentiation that was associated by increased glucose regulated c-peptide secretion. By contrast, concerted or sequential administration of the ectopic 3pTFs in an indirect hierarchical mode resulted in the generation of insulin and somatostatin co-producing cells and diminished glucose regulated processed insulin secretion. In conclusion transcription factors induced liver to pancreas transdifferentiation is a progressive and hierarchical process. It is reasonable to assume that this characteristic is general to wide ranges of tissues. Therefore, our findings could facilitate the development of cell replacement therapy modalities for many degenerative diseases including diabetes.

Clorhexidina y poliheximetil biguanida tópica para el manejo de queratitis por acanthamoeba / Chlorhexidine and polyhexamethyl biguanide in the treatment of acanthamoeba keratitis

Evaluar la eficacia de la clorhexidina y la poliheximetil biguanida (PHMB) en el tratamiento de la queratitis por Acanthamoeba spp en usuarios de lentes de contacto (LC). Se realizó un estudio prospectivo donde participaron 3 pacientes con diagnóstico de queratitis por acanthamoeba. Se tomó muestra de la lesión corneal, de fondos de saco, de los LC y sistemas de cuidado diario de los mismos; para análisis bacteriológico, parasitológico y micológico. Al confirmarse el diagnóstico de Acanthamoeba spp los pacientes fueron tratados con clorhexidina (0,02 por ciento) y PHMB tópicas. De los tres pacientes estudiados, 100 por ciento fueron del sexo femenino. La edad promedio fue de 29,3 años. Ojo rojo, secreción, dolor, visión borrosa y sensación de cuerpo extraño motivaron la consulta. El promedio de días entre el inicio de los síntomas y la primera consulta especializada fue de ± 9,6 días. Al ingreso el tamaño de las lesiones corneales varió entre 30-90 por ciento, dos de las cuales tenía el halo epitelial perilesional. El tratamiento específico se inició tardíamente (± 11,3 días después del ingreso) debido a la dificultad para obtener la clorhexidina y la PHMB, las cuales no están disponibles en nuestro país. El tiempo promedio de tratamiento fue de ± 44,6 días, obteniéndose mejoría de la lesión corneal, síntomas y de la vascularización. La combinación clorhexidina - PHMB podría ser una alternativa terapéutica para la queratitis por Acanthamoeba. Es necesaria la disponibilidad de los fármacos en nuestro país, que permita el tratamiento oportuno

Elaboración de un modelo experimental de quemaduras II: estudio del sexo, edad, peso, tiempo de exposición y supervivencia

Se revisa la literatura sobre modelos experimentales de quemaduras. Se presentan las experiencias obtenidas en el estudio del sexo, edad, peso, tiempo de expocisión y supervivencia de ratones albinos utilizados en el desarrollo de un modelo de enfermedad por quemadura. Los resultados obtenidos se exponen y analizan concluyéndose la utilidad del ratón albino para modelar la quemadura, recomendando el animal macho de 24.1 a 26 gramos y un tiempo de exposición a la quemadura seca de 10-20 seg. para el estudio de la patogenia y el diagnótico de la enfermedad por quemadura(AU)