Neuronorma Colombia: aportes y características metodológicas / Neuronorma Colombia: Contributions and methodological characteristics

Introducción Al realizar una evaluación neuropsicológica, es necesario contar con datos normativos adecuados; la calidad metodológica de los estudios que los proponen garantiza que las conclusiones sean confiables y válidas. Se presentan las características metodológicas del Proyecto Neuronorma Colombia con el fin de analizar sus aportes y limitaciones. Método Se exponen las características de la muestra normativa, los criterios de inclusión y exclusión, el análisis estadístico de los datos, el procedimiento para la obtención de datos normativos y los instrumentos utilizados. Resultados Se presentan algunos perfiles gráficos de ejecución de casos clínicos, a partir de la Unidad de Trabajo Neuronorma, con el fin de ilustrar la interpretación de los resultados obtenidos al evaluar pacientes con la batería Neuronorma Colombia. Discusión y conclusiones Existen ventajas metodológicas del estudio: su carácter multicéntrico y conormalizado y disponer de la Unidad de Trabajo Neuronorma, que permite obtener perfiles gráficos del desempeño del paciente, herramienta fundamental para el diagnóstico y la investigación. Se presentan los hallazgos de investigaciones posteriores realizadas a partir de los datos normativos propuestos, que son evidencia de la utilidad de la batería. Se discute el aporte de este estudio, en el contexto de sus antecedentes inmediatos. (AU)

Introduction Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. Method We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. Results We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. Discussion and conclusions Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background. (AU)

Neuronorma Colombia: aportes y características metodológicas / Neuronorma Colombia: Contributions and methodological characteristics

Introducción Al realizar una evaluación neuropsicológica, es necesario contar con datos normativos adecuados; la calidad metodológica de los estudios que los proponen garantiza que las conclusiones sean confiables y válidas. Se presentan las características metodológicas del Proyecto Neuronorma Colombia con el fin de analizar sus aportes y limitaciones. Método Se exponen las características de la muestra normativa, los criterios de inclusión y exclusión, el análisis estadístico de los datos, el procedimiento para la obtención de datos normativos y los instrumentos utilizados. Resultados Se presentan algunos perfiles gráficos de ejecución de casos clínicos, a partir de la Unidad de Trabajo Neuronorma, con el fin de ilustrar la interpretación de los resultados obtenidos al evaluar pacientes con la batería Neuronorma Colombia. Discusión y conclusiones Existen ventajas metodológicas del estudio: su carácter multicéntrico y conormalizado y disponer de la Unidad de Trabajo Neuronorma, que permite obtener perfiles gráficos del desempeño del paciente, herramienta fundamental para el diagnóstico y la investigación. Se presentan los hallazgos de investigaciones posteriores realizadas a partir de los datos normativos propuestos, que son evidencia de la utilidad de la batería. Se discute el aporte de este estudio, en el contexto de sus antecedentes inmediatos. (AU)

Introduction Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. Method We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. Results We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. Discussion and conclusions Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background. (AU)

Neuronorma Colombia: contributions and methodological characteristics.

INTRODUCTION: Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. METHOD: We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. RESULTS: We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. DISCUSSION AND CONCLUSIONS: Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background.

Neuronorma Colombia: Contributions and methodological characteristics. / Neuronorma Colombia: aportes y características metodológicas.

INTRODUCTION: Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. METHOD: We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. RESULTS: We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. DISCUSSION AND CONCLUSIONS: Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background.

[Use of targeting therapy in Erdheim-Chester disease: A case report with neurologic involvement]. / Utilisation de thérapie ciblée dans la maladie d'Erdheim-Chester : à propos d'un cas avec atteinte du système nerveux central.

INTRODUCTION: Erdheim-Chester disease (ECD) is a rare multisystemic disease characterised by an infiltration of various organs by CD68+ CD1a- histiocytes. The clinical and radiological presentation is very variable. CASE REPORT: We report the case of a 71-year-old woman with ECD which was revealed by neurological and cutaneous manifestations. The diagnosis was confirmed by skin biopsy and the BRAFV600E mutation was identified in skin tissue, leading to the use of combined therapy targeting the RAS-RAF-ERK-MEK pathway. This therapy allowed an improvement of cutaneous manifestations but neurological manifestations lead to death, underlying their notable severity. CONCLUSION: Our case report shows the persistent diagnostic difficulty of the ECD and the particular gravity of neurologic involvement.

[Validity and reproducibility of two direct observation assessment forms for evaluation of internal medicine residents' clinical skills]. / Validité et reproductibilité de deux grilles d'observation des compétences cliniques des internes en DES de médecine interne.

INTRODUCTION: The revision of the French medical studies' third cycle ought to be competency-based. In internal medicine, theoretical and practical knowledge will be assessed online with e-learning and e-portfolio. In parallel, a reflection about clinical skills assessment forms is currently ongoing. In this context, our aim was to assess the reproducibility and validity of two assessment forms based on direct clinical observation. METHOD: A prospective and multicentric study has been conducted from November 2015 to October 2016 aiming at evaluating the French translations of the MINI-Clinical Examination Exercice (MINI-CEX) and the Standardized Patient Satisfaction Questionnaire (SPSQ). Included residents have been assessed 2 times over a period of 6 months by the same binoma of judges. RESULTS: Nineteen residents have been included. The inter-judge reproducibility was satisfactory for the MINI-CEX: intraclass coefficients (ICC) between 0.4 and 0.8 and moderate for the SPSQ: ICC between 0.2 and 0.7 with a good internal coherence for both questionnaires (Cronbach between 0.92 and 0.94). Significant differences between the distributions of the scores given by the judges and a significant inter-center variability have been found. CONCLUSION: If the absolute value of the scores should not be taken into account in the evaluation process given its high variability, it could be of interest for the follow-up of the progression in the competencies. These forms could support the residents' debriefing based on the general trends given by the scores.

Short-term methionine supplementation during the early post-partum period in primiparous rabbits improves prolificacy associated with an increase in serum concentrations of IGF-I.

The aim of this study was to evaluate the effects of methionine supplementation on energy metabolism and reproductive performance during the early post-partum period in primiparous does. Forty nulliparous New Zealand White does were used. Females were randomized in two groups at calving: the control group (n = 20) was fed with the basal diet, and the methionine group (n = 20) was fed the basal diet plus 1 g/animal/day of methionine from the day of calving to 4 days post-partum. Results showed that methionine supplementation increased (p = 0.032) the concentration of insulin-like growth factor-1 with respect to control group 4 days post-partum. It similarly increased the prolificacy (p = 0.03), the number of kits born alive per litter (p = 0.06) and the body gain weight of the litter during supplementation (p = 0.035). These results were observed despite the does in the methionine group having a deeper negative energy balance than the does in the control group. Finally, methionine supplementation did not affect receptivity (p = 0.23), fertility (p = 0.49), the number of kits born dead per litter (p = 0.86) insulin and metabolites as glucose, non-esterified fatty acids and triglycerides. In conclusion, our results show that methionine supplementation during the first 4 days of the post-partum period in rabbits increases total litter size and the corporal weight of kits and is associated with an increase in blood concentration of IGF-1.

BAFF and BAFF-R levels are associated with risk of long-term kidney graft dysfunction and development of donor-specific antibodies.

There are lines of evidence that B cells may play a role in transplantation. B cell activating factor, BAFF, is a homotrimer that has been shown to play a role in B cell survival, maturation and activation. To date, little is known of the role of BAFF and its receptors in transplantation. We analyzed the level of BAFF mRNA and its soluble protein, as well as transcripts coding for its receptors, BAFF-R, TACI and BCMA, in the blood of 143 patients with stable kidney transplant function 5 years or more posttransplantation. Three endpoints were analyzed: the time to renal dysfunction, the time to appearance of anti-HLA antibodies and the time to development of donor-specific antibodies. We established threshold values for BAFF and BAFF-R and showed that (1) stable patients with high BAFF-R levels had a higher risk of developing graft dysfunction, (2) patients with lower levels of BAFF transcripts or a higher level of soluble BAFF had a significantly higher risk of developing donor-specific antibodies. These data suggest that BAFF constitutes a risk factor for renal graft dysfunction and development of donor-specific antibodies. They also suggest that agents targeting BAFF-R interactions may offer new therapeutic opportunities in transplantation.

The association between CDC42 and caveolin-1 is involved in the regulation of capacitation and acrosome reaction of guinea pig and mouse sperm.

In the mammalian sperm, the acrosome reaction (AR) is considered to be a regulated secretion that is an essential requirement for physiological fertilization. The AR is the all-or-nothing secretion system that allows for multiple membrane fusion events. It is a Ca(2)(+)-regulated exocytosis reaction that has also been shown to be regulated by several signaling pathways. CDC42 has a central role in the regulated exocytosis through the activation of SNARE proteins and actin polymerization. Furthermore, the lipid raft protein caveolin-1 (CAV1) functions as a scaffold and guanine nucleotide dissociation inhibitor protein for CDC42, which is inactivated when associated with CAV1. CDC42 and other RHO proteins have been shown to localize in the acrosome region of mammalian sperm; however, their relationship with the AR is unknown. Here, we present the first evidence that CDC42 and CAV1 could be involved in the regulation of capacitation and the AR. Our findings show that CDC42 is activated early during capacitation, reaching an activation maximum after 20 min of capacitation. Spontaneous and progesterone-induced ARs were inhibited when sperm were capacitated in presence of secramine A, a specific CDC42 inhibitor. CAV1 and CDC42 were co-immunoprecipitated from the membranes of noncapacitated sperm; this association was reduced in capacitated sperm, and our data suggest that the phosphorylation (Tyr14) of CAV1 by c-Src is involved in such reductions. We suggest that CDC42 activation is favored by the disruption of the CAV1-CDC42 interaction, allowing for its participation in the regulation of capacitation and the AR.

Glutathione monoethyl ester improves functional recovery, enhances neuron survival, and stabilizes spinal cord blood flow after spinal cord injury in rats.

Secondary damage after spinal cord (SC) injury remains without a clinically effective drug treatment. To explore the neuroprotective effects of cell-permeable reduced glutathione monoethyl ester (GSHE), rats subjected to SC contusion using the New York University impactor were randomly assigned to receive intraperitoneally GSHE (total dose of 12 mg/kg), methylprednisolone sodium succinate (total dose of 120 mg/kg), or saline solution as vehicle. Motor function, assessed using the Basso-Beattie-Bresnahan scale for 8 weeks, was significantly better in GSHE (11.2+/-0.6, mean+/-S.E.M., n=8, at 8 weeks) than methylprednisolone (9.3+/-0.6) and vehicle (9.4+/-0.7) groups. The number of neurons in the red nuclei labeled with FluoroRuby placed caudally to the injury site was significantly higher in GSHE (158+/-9.3 mean+/-S.E.M., n=4) compared with methylprednisolone (53+/-14.7) and vehicle (46+/-16.4) groups. Differences in the amount of spared SC tissue at the epicenter and neighboring areas were not significant among experimental groups. In a second series of experiments, using similar treatment groups (n=6), regional changes in microvascular SC blood flow were evaluated for 100 min by laser-Doppler flowmetry after clip compression injury. SC blood flow fell in vehicle-treated rats 20% below baseline and increased significantly with methylprednisolone approximately 12% above baseline; changes were not greater than 5% in rats given GSHE. In conclusion, GSHE given to rats early after moderate SC contusion/compression improves functional outcome and red nuclei neuron survival significantly better than methylprednisolone and vehicle, and stabilizes SC blood flow. These results support further investigation of reduced glutathione supplementation after acute SC injury for future clinical application.

Nutrient intake and gastric cancer in Mexico.

In contrast to the decreasing trends observed in most countries, gastric-cancer mortality has remained at about the same level in Mexico throughout the last 40 years. As part of a study carried out in the metropolitan area of Mexico City, an assessment of nutrient intake and gastric cancer is presented here. The study population comprised 220 cases of gastric cancer and 752 population-based controls. Our results showed 70 to 80% reduction in the risk of developing this tumor, associated with the intake of polyunsaturated fat, fiber and vitamin E; and this effect was independent of the histological type of the tumor (i.e., intestinal or diffuse). On the other hand, an increased risk of gastric cancer was related to the consumption of saturated fat (OR(Q4vs.Q1) = 4.37, 95% CI 1.89-10.12) and, cholesterol (OR(Q4vs.Q1) = 2.39, 95% CI 1.23-4.64), but such effects were restricted to the intestinal type of gastric cancer. In the whole study population, mono-unsaturated fat intake increased the risk for gastric cancer, and a marginally significant increasing trend was observed for protein consumption. The findings from this study add information about the role of specific nutrients in the etiology of gastric cancer.

Alcohol consumption and gastric cancer in Mexico.

This paper presents an assessment of alcohol consumption, including the popular Mexican liquor tequila, in relation to the incidence of gastric cancer. We conducted a population-based case-control study in Mexico City, with 220 gastric cancer cases and 752 population-based controls. A food frequency questionnaire was used to measure consumption of alcohol and other dietary items. Grams of ethanol were estimated by the Food Intake Analysis System 3.0 software. After adjustment for known risk factors, wine consumption was positively associated with the risk of developing gastric cancer (OR=2.93; CI 95% 1.27-6.75) in the highest category of wine consumption, corresponding to at least 10 glasses of wine per month, with a significant trend (p=0.005). This association remained among intestinal (OR=2.16; CI 95% 0.68-6.92, p-value for trend=0.031 ) and diffuse (OR=4.48; CI 95% 1.44-13.94, p-value for trend=0.018 ) gastric cancer cases. A borderline significant trend between GC risk and total ethanol intake was observed (p=0.068). Consumption of beer and distilled alcoholic beverages including brandy, rum, and tequila was not associated with GC risk. The results indicate the need to focus on the study of the potential effects of different types of wine, with emphasis on components other than ethanol regarding the incidence of gastric cancer, even among populations with moderate to low levels of alcohol consumption.

Transitory expression of NADPH diaphorase (NOS) in axonal swellings after spinal cord injury.

To investigate the sites of nitric oxide synthase (NOS) expression after a spinal cord (SC) injury, NADPH-d diaphorase histochemistry was performed in the SC of adult rats sacrificed at different times from 1 h to 90 days after both SC contusion or transection. NOS could first be seen 12 h after injury in axonal swellings (AS) (club shaped structures at the tip of damage axons, associated with tissue destruction). NOS expression reached a maximum 3 days after injury, and gradually disappeared after 7 days. Finally, AS collapsed leaving behind microcysts. NOS expression and the consequent production of nitric oxide could be involved in the pathophysiology of the secondary damage, and/or could reflect a failed attempt for axonal regeneration.

Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury.

The pharmacokinetics of the immunosuppressive agent cyclosporin-A (CsA) were studied in rats submitted to spinal cord (SC) injury. A single CsA 10 mg/kg dose was given either intraperitoneally (i.p.) or orally to rats submitted to experimental SC injury at the T8 level. Twenty four hours after lesion (acute stage of SC injury) i.p. CsA bioavailability was increased, while t1/2 was prolonged. However, oral bioavailability was reduced. Seven weeks after lesion (chronic stage of SC injury) CsA bioavailability, by either route, was not significantly different from control values. Results indicate that parenteral CsA bioavailability is increased during the acute stage of SC lesion, probably due to an impaired elimination. Oral bioavailability, however, is decreased, since there is also an important reduction in gastrointestinal CsA absorption that overrides the effect of impaired elimination. Alterations in CsA pharmacokinetics appear to revert during the chronic stage of SC injury. Changes in CsA bioavailability, depending on the route of administration and on time, must be considered to design an adequate immunosuppressive treatment in SC injury.

Histochemical evidence of the increased expression of nicotinamide adenine dinucleotide phosphate-dependent diaphorase in neurons of the myenteric plexus after acute spinal cord injury in adult rats.

The expression of nitric oxide synthase in neurons of the gastrointestinal tract (GIT) after experimental spinal cord injury (SCI) was assessed in adult rats contused at T8. One day and 10 weeks after injury, specimens along the GIT were studied for NADPH-diaphorase histochemistry. A significant increase in the number of positive cell bodies and fibers in the myenteric plexus were observed 1 day after SCI, as compared to specimens from control and chronically injured rats, with the exception of the colon, which showed unchanged or decreased number of positive neurons in the acute and chronic stages, respectively. Positive neurons in the submucous plexus remained unchanged, excepting an increase in the colon after acute SCI, and a decrease in the duodenum in chronically injured rats. The altered nitric oxide neurotransmission in the GIT may be relevant to its reduced motility after SCI.

Sperm protein (sp50) binds to acrosome and plasma membranes in a Ca(2+)-dependent manner: possible role in acrosome reaction.

Annexins are a family of Ca(2+)-binding proteins involved in the exocytotic process. The presence and the role of annexins in mammalian spermatozoa have not been well established. Two annexin-like proteins were obtained from guinea pig testis, a doublet of Mr 31-33 kD (p31/33) and a protein of Mr 50 kD (p50). Both proteins were able to bind to erythrocyte ghosts in a Ca(2+)-dependent fashion. Polyclonal antibodies against p31/33 reacted with two major proteins, Mrs 50 kD (sp50) and 42 kD (sp42), from mature and immature guinea pig spermatozoa. p50 and sp50 are likely the native proteins from testis and spermatozoa, respectively, and they are seemingly related. By immunofluorescence, sp50 was only found in the acrosome region of immature and capacitated and noncapacitated spermatozoa, and its location was intracellular. In spermatozoa undergoing acrosome reaction, sp50 was detected in the whole acrosome, while in spermatozoa that had undergone acrosome reaction sp50 was not detected. However, in the protein pattern of acrosome reaction vesicles, anti-p31/33 antibody revealed diffuse bands of Mr 35-38 kD. sp50 was able to bind to plasma membrane fragments and acrosome outer membrane from demembranated sperm in a Ca(2+)-dependent fashion. The presence of sp50 in the acrosome region, its distribution throughout the acrosome membrane just before the acrosome reaction, and its ability to bind both plasma and outer acrosome membranes in a Ca(2+)-dependent manner suggest that sp50 may participate in the acrosome reaction mechanism in guinea pig spermatozoa.