Clinical utility of Phototest via teleneuropsychology in Chilean rural older adults / Utilidade clínica do phototest via teleneuropsicologia em idosos rurais chilenos

ABSTRACT. The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

RESUMO. A pandemia de COVID-19 mostrou a necessidade de cuidados neuropsicológicos para adultos idosos com queixas de memória em diferentes contextos, incluindo áreas rurais ou áreas de difícil acesso. Objetivo: Analisar a utilidade clínica do Phototest, por meio da telemedicina, para identificar uma leve deficiência cognitiva em adultos idosos rurais com queixas de memória, durante a pandemia de COVID-19. Métodos: Realizamos uma comparação transversal, caso-controle e utilidade clínica dos testes cognitivos breves. Amostra: Cento e onze idosos rurais com deficiência cognitiva leve (DCL) e 130 controles saudáveis da região de Los Lagos, Chile. Instrumentos: Minimental modificado (MMSEm) e versão do teste fotográfico (PT) adaptada para o Chile. Resultados: Para identificar a DCL, usando pontuação de corte de 27-28 pontos, o Phototest mostrou sensibilidade de 96,6% e especificidade de 81,8%; indicadores superiores aos do MMSEm. Conclusões: O Phototest é mais preciso que o MMSEm para identificar, por meio da telemedicina, alterações cognitivas em adultos idosos rurais com queixas de memória cognitiva. Sendo assim, seu uso na atenção primária é recomendado para realizar a detecção precoce de alterações cognitivas pré-clínicas em DCL ou doenças neurodegenerativas.

Clinical utility of Phototest via teleneuropsychology in Chilean rural older adults.

The COVID-19 pandemic has shown the need for neuropsychological care for older adults with memory complaints in different contexts, including rural areas or areas with difficult access. Objective: This study aimed to analyze the clinical utility of the Phototest, through telemedicine, to identify mild cognitive impairment in rural older adults with memory complaints, during the COVID-19 pandemic. Methods: We performed a cross-sectional, case-control, and clinical utility comparison of brief cognitive tests (BCTs). The sample included 111 rural elderly people with mild cognitive impairment (MCI) and 130 healthy controls from the Los Lagos region, Chile. The instruments adopted were modified Mini-Mental State Examination (MMSEm) and adapted version of the Phototest (PT) for Chile. Results: To identify mild cognitive impairment, using a cutoff score of 27-28 points, the Phototest showed a sensitivity of 96.6% and a specificity of 81.8%; indicators superior to those of the MMSEm. Conclusions: The Phototest is more accurate than the MMSEm in identifying cognitive alterations in rural older adults with cognitive memory complaints through telemedicine. Therefore, its use in primary care is recommended in order to perform early detection of preclinical cognitive alterations in mild cognitive impairment or neurodegenerative diseases.

A pandemia de COVID-19 mostrou a necessidade de cuidados neuropsicológicos para adultos idosos com queixas de memória em diferentes contextos, incluindo áreas rurais ou áreas de difícil acesso. Objetivo: Analisar a utilidade clínica do Phototest, por meio da telemedicina, para identificar uma leve deficiência cognitiva em adultos idosos rurais com queixas de memória, durante a pandemia de COVID-19. Métodos: Realizamos uma comparação transversal, caso-controle e utilidade clínica dos testes cognitivos breves. Amostra: Cento e onze idosos rurais com deficiência cognitiva leve (DCL) e 130 controles saudáveis da região de Los Lagos, Chile. Instrumentos: Minimental modificado (MMSEm) e versão do teste fotográfico (PT) adaptada para o Chile. Resultados: Para identificar a DCL, usando pontuação de corte de 27-28 pontos, o Phototest mostrou sensibilidade de 96,6% e especificidade de 81,8%; indicadores superiores aos do MMSEm. Conclusões: O Phototest é mais preciso que o MMSEm para identificar, por meio da telemedicina, alterações cognitivas em adultos idosos rurais com queixas de memória cognitiva. Sendo assim, seu uso na atenção primária é recomendado para realizar a detecção precoce de alterações cognitivas pré-clínicas em DCL ou doenças neurodegenerativas.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology. The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is "central" fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients. This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.

Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats.

INTRODUCTION: In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. METHODS: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). DISCUSSION/CONCLUSION: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.

Analysis of the Increase in Bone Mineral Density After Surgical Treatment of Primary Hyperparathyroidism.

AIM: To analyze the effect of the surgery in bone mineral density (BMD) and to study the value of preoperative clinical and analytical factors as predictors of bone increase. MATERIAL AND METHODS: Prospective observational study. Postmenopausal women who were operated for primary hyperparathyroidism were included. A bone densitometry of the lumbar spine and femoral neck and analytical determinations (parathyroid hormone [PTH], alkaline phosphatase, albumin, phosphate, creatinine, 25-hydroxy-vitamin D3, creatinine clearance, and calciuria) were performed previous to the intervention and after 12 months from surgery. RESULTS: Two hundred and twenty-eight patients were operated on for primary hyperparathyroidism were considered for study, 108 postmenopausal women entered in the final analysis. The mean age was 63 ± 7 yr. After the intervention, a significant increase in BMD was observed in the two locations analyzed, although this increase was significant greater at the level of the lumbar spine. In the lumbar spine, 68 patients (63%) recorded a significant postoperative increase in bone density. Median postoperative BMD was 0.860 g/cm2 (interquartile range: 0.93). The observed average percentage of density increase was 6.63 ± 17.9. In femoral neck, 61 patients (56.6%) registered a significant increase in bone density. Median postoperative BMD value was 0.741 g/cm2 (interquartile range: 0.76). The average percentage of density increase was 3.19 ± 17.9. In the lumbar spine, patients with osteoporosis before surgery increased postoperative BMD more frequently than those with osteopenia or normal density. Patients who increased BMD preoperatively presented lower bone density levels both in the lumbar spine (median: 0.775, interquartile range: 0.882) and in the hip (median: 0.655, interquartile range: 0.562) than patients in whom it was not observed postoperative increase. PTH preoperative serum was lower among patients who increased bone density in the femur (median: 141 pg/ml, interquartile range: 291) than among those who did not (median: 152 pg/ml, interquartile range: 342) (p = 0.01). In the multivariate analysis, the increase in BMD in the lumbar spine was related to preoperative BMD (odds ratio [OR] 0.084, 95% confidence interval [CI]: 0.007-0.961); in femoral neck it was related to preoperative BMD (OR 0.001; 95% CI: 0.0-0.028) and to the preoperative PTH serum concentration (OR 0.99; 95% CI: 0.98-0.99). CONCLUSIONS: After surgery, a significant increase in BMD was observed in the lumbar spine and femoral neck. In the multivariate analysis, preoperative bone density was the factor that showed the highest predictive value of the increase in BMD after surgery.

Primary Hyperparathyroidism due to Parathyroid Adenoma Originated from Supernumerary Gland.

INTRODUCTION: The variability of the location of the parathyroid glands is directly related to the events that occur during embryonic development. The impact that an individual submits more than four parathyroid glands is close to 13%. However the presentation of a parathyroid adenoma in a supernumerary gland is an uncommon event. CASE REPORT: A 30-year-old man diagnosed with primary hyperparathyroidism with matching findings on ultrasonography and scintigraphy for parathyroid adenoma localization lower left regarding the thyroid gland. A cervicotomy explorer showed four orthotopic parathyroid glands. The biopsy of the inferior left gland was normal. No signs of adenoma were seen in the biopsy. Following mobilization of the ipsilateral thyroid lobe, fifth parathyroid gland was found increased significantly in size than proceeded to remove, confirming the diagnosis of adenoma. After the excision, the levels of serum calcium and parathyroid hormone were normalized. CONCLUSIONS: The presentation of a parathyroid adenoma in a supernumerary gland is a challenge for the surgeon. The high sensitivity having different imaging techniques has been a key to locate preoperatively the pathological parathyroid gland. Analytical or clinical persistence of primary hyperparathyroidism after parathyroid surgery can occur if the location of the adenoma is a supernumerary or ectopic gland location.

Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE).

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND METHODS: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.

Evaluation of a Method for Long-Term Cryopreservation of Fungal Strains.

The conservation of microorganisms is essential for their in-depth study. However, today's most widely used conservation methods, based on the use of distilled water, soil, oils, or silica, do not guarantee the stability of fungal cells, especially dermatophytes. This problem led us to evaluate the conservation capacity of a cryogenic vials system containing glass beads covered in a cryopreservant hypertonic solution as an alternative method of storage of fungal cells at -80°C. Up to 570 strains of fungi belonging to 27 different species, isolated from clinical samples, were inoculated into cryotubes containing 25 glass beads covered in a cryopreserving hypertonic solution. Suspensions were mixed vigorously and the cryopreserving solution was discarded. The tubes were frozen at -80°C for a period of 42 months and periodically, a glass bead was removed from each cryotube and inoculated onto Sabouraud dextrose agar, and incubated at 30°C for 7-14 days to evaluate the number of colonies recovered, their purity, and phenotypic characteristics. All yeast isolates were recovered, unlike 2 isolates (4.4%) of the mold group and 21 (10.7%) of the dermatophytes. Survival rates were close to 100% for yeasts and molds, with expiration times being estimated for almost indefinite stocks, and 62% for dermatophytes, with an average expiration date of 25.5 years. The phenotypic characteristics remained comparable to those of the strains before storage. Conservation at -80°C using cryogenic vials is a reliable and efficient system for the conservation of fungal collections, and although the behavior differs by groups, stratified survival data are obtained to avoid extinction.

Erratum to: Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

The original version of this article unfortunately contained a mistake. The name of author was changed from "Pascual Gargiulo" to "Pascual Ángel Gargiulo.

Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.

Perinatal injections of N-methyl-D-aspartate (NMDA) receptor antagonist in rodents emulate some cognitive impairments and neurochemical alterations, such as decreased GABAergic (gamma aminobutyric acid) interneuron immunoreactivity, also found in schizophrenia. These features are pervasive, and developing neuroprotective or neurorestorative strategies is of special interest. In this work, we aimed to investigate if a short exposure to enriched environment (EE) in early adulthood (P55-P73) was an effective strategy to improve cognitive dysfunction and to restore interneuron expression in medial prefrontal cortex (mPFC) and hippocampus (HPC). For that purpose, we administered MK-801 intraperitoneally to Long Evans rats from postnatal days 10 to 20. Twenty-four hours after the last injection, MK-801 produced a transient decrease in spontaneous motor activity and exploration, but those abnormalities were absent at P24 and P55. The open field test on P73 manifested that EE reduced anxiety-like behavior. In addition, MK-801-treated rats showed cognitive impairment in novel object recognition test that was reversed by EE. We quantified different interneuron populations based on their calcium-binding protein expression (parvalbumin, calretinin, and calbindin), glutamic acid decarboxylase 67, and neuronal nuclei-positive cells by means of unbiased stereology and found that EE enhanced interneuron immunoreactivity up to normal values in MK-801-treated rats. Our results demonstrate that a timely intervention with EE is a powerful tool to reverse long-lasting changes in cognition and neurochemical markers of interneurons in an animal model of schizophrenia.

Glutamate and modeling of schizophrenia symptoms: review of our findings: 1990-2014.

In the early 90s, we studied the role of perception disturbances in schizophrenia in our first clinical approaches, using the Bender test in schizophrenic patients. Results were clear, showing a shape discrimination failure. Following this initial results, we reproduced nuclear symptoms of schizophrenia in animal models, showing that perceptual disturbances, acquisition disturbances, decrease in affective levels and working memory disturbances can be induced by specific N-methyl-D-aspartic acid (NMDA) glutamatergic blockade within the nucleus accumbens septi (NAS). We studied also another glutamatergic and dopaminergic drugs, finding that a decrease in glutamatergic transmission within NAS led to cognitive disturbances and affective flattening. An increase in glutamatergic transmission fully enhances cognition in the tasks used. Dopaminergic D-2 antagonists partially improved cognition. Our results link the proposed corticostriatal dysfunction with the thalamocortical disturbances underlying perceptual problems, but also influencing affective levels and cognitive variables. According to our translational findings, core schizophrenia symptoms may be translationally reproduced antagonizing NMDA receptors within NAS, and improved blocking the glutamate auto-receptor. Dopaminergic transmission appears to have a role in therapeutic but not in the early pathophysiology of schizophrenia.

The thyroid hormone receptor ß induces DNA damage and premature senescence.

There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate-activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism.

Thyroid hormone receptors, cell growth and differentiation.

BACKGROUND: Tissue homeostasis depends on the balance between cell proliferation and differentiation. Thyroid hormones (THs), through binding to their nuclear receptors, can regulate the expression of many genes involved in cell cycle control and cellular differentiation. This can occur by direct transcriptional regulation or by modulation of the activity of different signaling pathways. SCOPE OF REVIEW: In this review we will summarize the role of the different receptor isoforms in growth and maturation of selected tissues and organs. We will focus on mammalian tissues, and therefore we will not address the fundamental role of the THs during amphibian metamorphosis. MAJOR CONCLUSIONS: The actions of THs are highly pleiotropic, affecting many tissues at different developmental stages. As a consequence, their effects on proliferation and differentiation are highly heterogeneous depending on the cell type, the cellular context, and the developmental or transformation status. Both during development and in the adult, stem cells are essential for proper organ formation, maintenance and regeneration. Recent evidence suggests that some of the actions of the thyroid hormone receptors could be secondary to regulation of stem/progenitor cell function. Here we will also include the latest knowledge on the role of these receptors in proliferation and differentiation of embryonic and adult stem cells. GENERAL SIGNIFICANCE: The thyroid hormone receptors are potent regulators of proliferation and differentiation of many cell types. This can explain the important role of the thyroid hormones and their receptors in key processes such as growth, development, tissue homeostasis or cancer. This article is part of a Special Issue entitled Thyroid hormone signalling.

Gastrointestinal stromal tumors: diagnosis and treatment.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. They originate from the interstitial cells of Cajal and are characterized by the overexpression of KIT protein (tyrosine kinase). Their prognosis has improved significantly with the discovery of imatinib mesylate for advanced GIST treatment. METHODS: We carried out a retrospective, descriptive study of GISTs diagnosed in our center during the past 5 years. We excluded patients with incidental diagnoses in the context of other pathologies because GIST did not affect outcome or prognosis. The variables studied were clinical characteristics, location, size, imaging techniques, resectability, neoadjuvant imatinib, surgical technique, histology, immunohistochemistry, prognostic classification of Fletcher, morbidity, monitoring, and disease-free and overall survival. RESULTS: Nineteen patients were diagnosed (14 males/5 females) with a mean age of 63 years (range: 30-84 years). Diagnosis was incidental in eight patients (42%). Tumor location of the remaining 11 patients (58%) was six tumors of the small intestine (55%), four gastric (36%) and one rectal (9%). Predominant gastrointestinal bleeding and anemia were diagnosed mainly by abdominal computed tomography (CT). At diagnosis, nine patients were considered resectable with radical intent (82%) and the other two patients (18%) received neoadjuvant treatment with a favorable response after 6 months. Three patients were treated with imatinib after surgery (33%). Median survival was 34 months (range: 5-58 months). CONCLUSIONS: Diagnosis of GIST is often incidental. The predominant clinical symptom is usually gastrointestinal bleeding and anemia and the most widely used imaging test is CT. Treatment is surgical unless advanced GIST is diagnosed, which will be treated with imatinib mesylate neoadjuvant therapy. A multidisciplinary approach to this pathology is essential, a fact that affects prognosis and patient survival.

Thyroid hormone regulation of APP (ß-amyloid precursor protein) gene expression in brain and brain cultured cells.

We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcriptional activity of the ß-amyloid precursor protein gene (APP) in cultured murine neuroblastoma cells, by a mechanism that involves binding of the nuclear thyroid hormone receptor (TR) to DNA sequences located within the first exon of the gene. In this report we present results showing that the thyroid hormones also repress the expression of APP in human neuroblastoma cells and in primary cultures of rat neurons. In addition, and in agreement with the results obtained in cultured cells, APP messenger RNA and protein levels are significantly higher in the brain of hypothyroid rats and mice, and also in Alzheimer-related brain regions dissected from KO mice lacking TRs. These results show that binding of the thyroid hormones to their nuclear receptors mediate their repressive effect on APP gene expression in vivo.

Monocyte-mediated regulation of genes by the amyloid and prion peptides in SH-SY5Y neuroblastoma cells.

Alzheimer's disease as well as prion-related encephalopathies are neurodegenerative disorders of the central nervous system, which cause mental deterioration and progressive dementia. Both pathologies appear to be primarily associated with the pathological accumulation and deposit of ß-amyloid or prion peptides in the brain, and it has been even suggested that neurotoxicity induced by these peptides would be associated to essentially similar pathogenic mechanisms, in particular to those that follow the activation of microglial cells. To probe whether the neurotoxic effects induced by the ß-amyloid and prion peptides are actually mediated by similar glial-associated mechanisms, we have examined the differential expression of genes in SH-SY5Y neuroblastoma cells incubated with conditioned media from ß-amyloid or prion-stimulated THP-1 monocytic cells. According to microarray analysis, not many coincidences are observed and only four genes (Hint3, Psph, Daam1 and c-Jun) appear to be commonly upregulated by both peptides. Furthermore, c-Jun appears to be involved in the cell death mediated by both peptides.

Early thyroid hormone-induced gene expression changes in N2a-ß neuroblastoma cells.

Thyroid hormone has long been known to regulate neural development. Hypothyroidism during pregnancy and early postnatal period has severe neurological consequences including even mental retardation. The purpose of this study was to characterize gene expression pattern during thyroid hormone-induced differentiation of neuro-2a ß cells in order to select "direct response genes" for further analysis. In this neuroblastoma cell line, thyroid hormone blocks proliferation and induces differentiation. Changes in gene expression level were examined after a T3 treatment of 3 and 24 h using cDNA arrays. Sixteen genes were significantly up-regulated and 79 down-regulated by T3 treatment. Five up-regulated genes not previously described as regulated by thyroid hormone and selected for their putative significance to understand T3 action on cell differentiation, were verified by RT-PCR analysis. The transcription factors Phox2a and basic helix-loop-helix domain containing, class B2 mRNAs exhibited a clear increase after 3- and 24-h treatment. The guanine-nucleotide exchange factor RalGDS was greatly up-regulated after 3-h treatment but not 24 h after. The results suggest an early involvement of these genes in T3 action during neuroblastoma cell differentiation probably mediating later changes in gene expression pattern.

Ruptura testicular traumática: papel de la exploración quirúrgica / Traumatic testicular rupture: the role of surgical exploration

Se presenta un hombre de 20 años de edad que sufre lesión traumática testicular durante práctica de artes marciales. Se discute el papel de la ecografía y de la exploración quirúrgica.

We present a man 20 years of age that suffered a traumatic testicular injury during the practice of martial arts. The role of echography and surgical exploration are discussed.

Proceso de duelo en familiares y cuidadores / Grieving among relatives and caregivers

En este artículo se dan una definición y una descripción del duelo basadas en sus características y en los modelos explicativos en vigencia (modelo de etapas, modelo de tareas, modelo dual y modelo constructivista). Se afirma que en los procesos de demencia se produce un duelo anticipado como consecuencia de una pérdida relacional significativa antes de la muerte, y se describen los factores de riesgo de duelo complicado en cuidadores: sobrecarga, falta de recursos personales, materiales, delegación de cuidados y sentimientos complejos como la culpa. También se señala la conveniencia de que las organizaciones asistenciales faciliten a los profesionales los medios adecuados para ayudar en los duelos y elaborar los suyos propios como medida de prevención del quemado. Estos medios pueden incluir protocolos de duelo que contemplen la intervención con la familia, el cuidador principal, otros pacientes y/o residentes y el equipo profesional cuidador. Para terminar, se afirma que las pérdidas de las personas con demencia tienen que ser consideradas evitando fenómenos, como el silenciamiento y la sobreprotección, facilitando la acogida y el acompañamiento de su dolor, de manera que no se produzcan enmascaramientos y complicaciones de índole orgánica y emocional (AU)

This article provides a definition and description of grief, its characteristics, and the current explanatory models of this phenomenon (the stage model, task model, constructivist model and dual process model). The authors argue that a state of mourning in advance is produced in the process of dementia as a result of significant relational loss before death and describe the risk factors for complicated grief in caregivers: overload, lack of personal and material resources, delegation of care, and complex feelings such as guilt. The need for healthcare organizations to provide professional caregivers with the appropriate means to help with grief and to develop their own measures to prevent burnout is stressed. These measures could include protocols that provide bereavement intervention with the family, the primary caregiver, other patients and/or residents and the professional caregiving team. Finally, losses in persons with dementia must be taken into consideration, avoiding phenomena such as silencing and overprotection and encouraging acceptance and emotional support of their pain so that organic and emotional complications do not occur (AU)