Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Complicaciones de la analgesia continua invasiva para el control del dolor agudo postoperatorio en un hospital de tercer nivel. Incidencia de complicaciones técnicas y uso de métodos de analgesia alternativos / Complications of continuous catheter analgesia for postoperative pain management in a tertiary care hospital. Incidence of technical complications and alternative analgesia methods used

Antecedentes: La analgesia continua invasiva es el método de referencia para el manejo del dolor postoperatorio en cirugía mayor pero no está exenta de posibles complicaciones. Existe poca información sobre las complicaciones de las técnicas analgésicas continuas con catéter (TACC) y su impacto en el control del dolor. Material y métodos: Diseñamos un estudio prospectivo longitudinal incluyendo a pacientes tratados mediante cirugía que recibieron una TACC postoperatoria. Se registraron el tipo de analgesia, la intensidad del dolor mediante escala NRS, las características de las TACC, sus complicaciones técnicas y la satisfacción de los pacientes. Se aplicó estadística descriptiva y análisis comparativo mediante t de Student. Resultados: Se registraron datos de 106 pacientes. La duración de las TACC fue 47,52 ± 21,23 h; 52 pacientes (49,1%) fueron controlados en hospitalización convencional y 54 (50,9%) en unidades de críticos o alta dependencia. La tasa global de complicaciones técnicas fue del 9,43%. Las complicaciones más frecuentes fueron desplazamiento del catéter (2,38%), inflamación en el punto de inserción del catéter IV (2,38%) y dosificación excesiva de analgésicos (2,38%). El valor medio de NRS fue ≤ 3 durante la permanencia de la TACC. La intensidad máxima de dolor fue mayor en los pacientes con complicaciones técnicas (media ± desviación estándar [x̅ ± DE]: 4,4 ± 2,8 vs. 2,9 ± 1,9; p < 0,05). La satisfacción con la comodidad de la técnica y la satisfacción global con el tratamiento del dolor se redujeron significativamente en presencia de complicaciones. Conclusiones: La incidencia de complicaciones técnicas de las TACC fue del 9,43% y tuvieron un impacto negativo en el control del dolor postoperatorio y en la satisfacción de los pacientes

Background: Continuous invasive analgesia remains the gold-standard method for managing acute post-operative pain after major surgery. However, this procedure is not exempt from complications that may have detrimental effects on the patient and affect the post-operative recovery process. Data of the complications of continuous catheter analgesic techniques (CCATs) and their impact on pain relief are scarce in the literature. Material and methods: We conducted a prospective longitudinal study and patients who underwent a surgical procedure and received continuous invasive analgesia after surgery were included. Post-operative analgesic strategy, pain scores (NRS), CCAT's characteristics and technical complications were recorded. Patient satisfaction was determined. Descriptive statistics and Student's t-tests were applied for the comparative analyses. Results: We collected data from 106 patients. Mean duration of the CCAT was 47.52±21.23hours and 52 patients (49.1%) were controlled in conventional hospitalisation units whereas 54 patients (50.9%) were controlled on intensive or high-dependency care units. The overall incidence of technical complications was 9.43%. The most common complications were catheter displacement (2.38%), inflammation at the IV catheter insertion point (2.38%) and excessive dosing of analgesic drugs (2.38%). Mean NRS scores were ≤3 during the permanence of CCATs. Maximum pain intensity was significantly higher in patients who suffered technical complications (mean±standard deviation [x̅ ± SD]: 4.4 ± 2.8 vs. 2.9 ± 1.9; P<0.05). Satisfaction levels with the technique and overall satisfaction with the pain management strategy were negatively impacted by the occurrence of complications. Conclusions: The incidence of technical complications of CCATs was 9.43% and had a negative impact in pain control and patient's satisfaction

Complications of continuous catheter analgesia for postoperative pain management in a tertiary care hospital. Incidence of technical complications and alternative analgesia methods used. / Complicaciones de la analgesia continua invasiva para el control del dolor agudo postoperatorio en un hospital de tercer nivel. Incidencia de complicaciones técnicas y uso de métodos de analgesia alternativos.

BACKGROUND: Continuous invasive analgesia remains the gold-standard method for managing acute post-operative pain after major surgery. However, this procedure is not exempt from complications that may have detrimental effects on the patient and affect the post-operative recovery process. Data of the complications of continuous catheter analgesic techniques (CCATs) and their impact on pain relief are scarce in the literature. MATERIAL AND METHODS: We conducted a prospective longitudinal study and patients who underwent a surgical procedure and received continuous invasive analgesia after surgery were included. Post-operative analgesic strategy, pain scores (NRS), CCAT's characteristics and technical complications were recorded. Patient satisfaction was determined. Descriptive statistics and Student's t-tests were applied for the comparative analyses. RESULTS: We collected data from 106 patients. Mean duration of the CCAT was 47.52±21.23hours and 52 patients (49.1%) were controlled in conventional hospitalisation units whereas 54 patients (50.9%) were controlled on intensive or high-dependency care units. The overall incidence of technical complications was 9.43%. The most common complications were catheter displacement (2.38%), inflammation at the IV catheter insertion point (2.38%) and excessive dosing of analgesic drugs (2.38%). Mean NRS scores were ≤3 during the permanence of CCATs. Maximum pain intensity was significantly higher in patients who suffered technical complications (mean±standard deviation [x̅ ± SD]: 4.4 ± 2.8 vs. 2.9 ± 1.9; P<0.05). Satisfaction levels with the technique and overall satisfaction with the pain management strategy were negatively impacted by the occurrence of complications. CONCLUSIONS: The incidence of technical complications of CCATs was 9.43% and had a negative impact in pain control and patient's satisfaction.

Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes.

AIM: This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. METHODS: This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53 mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia-defined by a 4% oxyhaemoglobin desaturation index ≥15-was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. RESULTS: Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7 mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P=0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06-5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13-5.34, model adjusted for waist-to-height ratio). CONCLUSION: Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.

Optic atrophy 1 mediates mitochondria remodeling and dopaminergic neurodegeneration linked to complex I deficiency.

Mitochondrial complex I dysfunction has long been associated with Parkinson's disease (PD). Recent evidence suggests that mitochondrial involvement in PD may extend beyond a sole respiratory deficit and also include perturbations in mitochondrial fusion/fission or ultrastructure. Whether and how alterations in mitochondrial dynamics may relate to the known complex I defects in PD is unclear. Optic atrophy 1 (OPA1), a dynamin-related GTPase of the inner mitochondrial membrane, participates in mitochondrial fusion and apoptotic mitochondrial cristae remodeling. Here we show that complex I inhibition by parkinsonian neurotoxins leads to an oxidative-dependent disruption of OPA1 oligomeric complexes that normally keep mitochondrial cristae junctions tight. As a consequence, affected mitochondria exhibit major structural abnormalities, including cristae disintegration, loss of matrix density and swelling. These changes are not accompanied by mitochondrial fission but a mobilization of cytochrome c from cristae to intermembrane space, thereby lowering the threshold for activation of mitochondria-dependent apoptosis by cell death agonists in compromised neurons. All these pathogenic changes, including mitochondrial structural remodeling and dopaminergic neurodegeneration, are abrogated by OPA1 overexpression, both in vitro and in vivo. Our results identify OPA1 as molecular link between complex I deficiency and alterations in mitochondrial dynamics machinery and point to OPA1 as a novel therapeutic target for complex I cytopathies, such as PD.

Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres.

AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. CONCLUSIONS: Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.

An outbreak of food poisoning due to a genogroup I norovirus.

Norovirus infection is associated with approximately 90% of epidemic non-bacterial acute gastroenteritis. The objective of this study is to describe an outbreak of norovirus genogroup I gastroenteritis which affected workers in a hospital and was attributed to food prepared by an infected food handler. Forty cases were detected, of whom 80% were interviewed. The index case was the cook employed in the hospital cafeteria. The following symptoms were observed: abdominal pain in 90.6%, vomiting in 71.9%, diarrhoea in 71.9%, general indisposition in 62.5%, headaches in 53.1% and fever in 32.4% of cases. The initial symptoms were abdominal pain in 37% and vomiting in 28%. Of the 14 samples analysed by RT-PCR, 12 (86%) were positive for a genogroup I norovirus. After sequencing the strain was identified as genotype Desert Shield. Many of the foodstuffs consumed were made by hand, favouring transmission from the index case to the cafeteria users.

[Iatrogenic hyperthyroidism secondary to weight loss medication. Predictive factors for their precocious detention]. / Hipertiroidismo yatrógeno secundario a cápsulas adelgazantes. Factores predictivos para su detección precoz.

OBJECTIVE: To establish the differential clinical characteristics between the Iatrogenic hyperthyroidism for not conventional medication for obesity treatment (weight losers) and the endogenous by Graves Basedow disease. PATIENT AND METHODS: Observational and analytical study, populational based, in the one which prospectively were compared cases with Iatrogenic hyperthyroidism (secondary to weight losers) with those with endogenous hyperthyroidism (Graves Basedow disease) as controls. Consisted of the variable clinical record of 100 correlative patients that consulted in specialized attention of endocrinology for Iatrogenic hyperthyroidism secondary to weight losers and for Graves Basedow disease. RESULTS: The differences observed between Iatrogenic hyperthyroidism (secondary to weight losers) (n = 43) as compared to endogenous hyperthyroidism (Graves Basedow disease) (n = 57) were: smaller age (31.8 +/- 10 as compared to 37.8 +/- 12.6 years), greater body mass index (27.6 +/- 7.2 as compared to 23.4 +/- 3.1), smaller goiter frequency (16.3% as compared to 84.2%) as well as absence of signs of ophthalmopathy (0% as compared to 57.9%). Both groups had low levels of TSH, and the difference rests in the values of free T4, low in the first group and increased in the endogenous hyperthyroidism. The odds ratio were: IMC > 27: 3.92 (0.91-16.72), age < 33 years: 5.58 (1.42-21.99), absence of goiter: 23.29 (6.39-84.85). The precedent of weight losers use was not selective of the first group, being detected in a 12.3% of cases of endogenous hyperthyroidism, though in periods of time remoter in relationship to the beginning of the clinic. CONCLUSIONS: In the differential diagnosis of a case of hyperthyroidism, it can be suspected Iatrogenic hyperthyroidism (secondary to weight losers) for medication for the obesity in patients of the feminine sex with overweight, without previous or familiar history of thyroid disease, and in those which in the physical exploration is not verified goiter neither ophthalmopathy.

[Iatrogenic hyperthyroidism. Report of an outbreak]. / Hipertiroidismo iatrógeno. A propósito de un brote epidémico.

The clinical observation of a series of 30 patients (age 29.6 +/- 9.8 years, 29 females and 1 male) who were remitted for evaluation of a thyroid dysfunction with a decrease in TSH and free thyroxin with clinical symptoms of hyperthyroidism and absence of goiter or exophthalmous is presented. Most of the patients (90%) had no family or personal history of previous thyroid disease. Anamnesis demonstrated the previous ingestion of uncommercialized prepared weight losers, dispensed in different areas off the pharmacy offices. Seventy-three percent of the patients had received the treatment from the same source (prescriber). In most of the cases (28 out of 30) normalization was observed in thyroid function tests. The demonstrated inefficacy of this medication as well as the health care importance of the problem are discussed.

[Dietary habits of 2 populations of the province of Barcelona (III): energy consumption and macronutrients]. / Hábitos alimentarios de dos poblaciones de la provincia de Barcelona (y III): consumo de energía y macronutrientes.

BACKGROUND: The identification of an association between alimentary and nutritional factors and different diseases has led to the study of alimentary habits in different populations. The consumption of energy and macronutrients was analyzed in two urban populations in the province of Barcelona (Spain). METHODS: One thousand thirty-four randomly selected individuals from primary care centers (PCC) were studied by a systematic sampling of all the out patient consultations over one year and to those to whom a semiquantitative questionnaire of frequency foodstuffs was given to estimate their normal diet. The subjects included all those residents in the two towns studied from 13 to 80 years of age who attended the PCC during the study period. RESULTS: The percentage of subjects from Vilanova i la Geltrú who were found to be high consumers of milk and derivatives, fish and vegetables was significantly higher in comparison with subjects from Gavá. The males of both towns presented a higher mean consumption of carbohydrates and energy than the females. On comparison of the consumption between the 2 populations, the mean carbohydrate diet ingested was significantly greater in the population from Gavá in both sexes as was the consumption of energy and total lipids between women and men, respectively. CONCLUSIONS: The population studied presented a clear pattern of Mediterranean diet consumption with elevated ingestion of carbohydrates and monounsaturated fats.

[Dietary habits of 2 populations of the province of Barcelona (I): design and validation of a semiquantitative questionnaire of frequency of food consumption]. / Hábitos alimentarios de dos poblaciones de la provincia de Barcelona (I): Diseño y validación de un cuestionario semicuantitativo de frecuencia de consumo de alimentos.

BACKGROUND: The identification of associations between alimentary factors and specific chronic diseases has led to the development of valid diet measurement methods. In the present article the design and validation of a questionnaire on the frequency of food consumption is reported. METHODS: From an initial sample of 1,034 inhabitants of two populations in the province of Barcelona, Spain, a sample stratified by age, sex and population of 64 individuals between 13-70 years of age was randomly selected. A semiquantitative questionnaire was initially given to 58 of the 64 subjects including 39 foods or groups of food and these were instructed as to how to follow a registry of food for 7 days in two different periods. The intakes of energy products, macronutrients, fiber, cholesterol and vitamins C, A and E were estimated by the two methods were compared. RESULTS: The means of nutrients estimated were lower in the questionnaire than those obtained by the reports of foods with the exception of the intake of carbohydrates. The range of the correlation coefficients for the values obtained by both methods was of 0.17 for vitamin E and 0.54 for the monounsaturated fatty acids which, after correction for the alternation factor, were found to be 0.20 and 0.67, respectively. Thirty-nine percent of the individuals were classified within the quintile of low consumption with 33% being within the quintile of greatest consumption. CONCLUSIONS: The use of a semiquantitative questionnaire may be useful to describe the dietary habits in a given population and fundamentally when the population studied is to be classified according to the normal consumption of energy and macronutrients.

[Dietary habits of 2 populations of the province of Barcelona (II): comparative study of the frequency of consumption in both populations and its relationship to recommended diet in diabetes]. / Hábitos alimentarios de dos poblaciones de la provincia de Barcelona (II): Estudio comparativo de la frecuencia de consumo en ambas poblaciones y su relación con la dieta recomendada en la diabetes.

BACKGROUND: The aim of the present study was to compare the eating habits of two urban populations (Vilanova i la Geltrú and Gavá) of the province of Barcelona, Spain, and determine the relation with the diet recommended in diabetes since this diet does not differ from what is considered "equilibrated diet". METHODS: One thousand thirty-four individuals randomly selected from Primary Health Care Centers (PHCC) by a systematic sampling of all the outpatient consultations over one year to whom a questionnaire on semiquantitative frequencies were studied with the aim of determining their everyday diet. All those between 13 and 80 years of age, residing in the two municipalities studied and who attended the PHCC over the period of the study were included in the study. RESULTS: On comparison of both populations a statistically higher consumption (p < 0.01) of milk products, fish, vegetables, fruits and oils was observed in Vilanova i la Geltrú than in Gavá. Both groups presented a lower intake than recommended of fish, vegetables, and fruits. In contrast a high intake of sugar, ice cream and sugared beverages and foods were observed in the two populations studied and in the younger are groups. CONCLUSIONS: The population of Vilanova i la Geltrú have dietary habits which are closer to those recommended in the diet of diabetics than the population of Gavá.

[Care for the diabetic patient in Catalonia. A study of a population sample]. / La asistencia al diabético en Cataluña. Estudio en una muestra de población. Grupo Catalán de Estudio de la Diabetes (GCED).

BACKGROUND: The aim of this study was to determine the clinical and therapeutic profile of both types of diabetics (IDDM and NIDDM) attended at different levels of health care in Cataluña in order to establish quality control and rationalize diabetologic sanitary planning. METHODS: Fifteen centers in Cataluña participated in a study with a total of 1,430 patients. The centers represented different specialized care levels: 6 endocrinology public health out-patient clinics (EO), 4 county hospitals (CH), 3 university hospitals (UH) and 2 private diabetic units (DU). RESULTS: IDDM: a) the percentage was higher in UH and DU (39 and 37) than in CH (26 p less than 0.01) and EO (11 p less than 0.001); b) the youngest were attended in UH (24 +/- 14 years) and the oldest in the EO (39 +/- 17 years, p less than 0.001), occupying the CH and DU at an intermediate position (34 +/- 16 and 32 +/- 17 years) and different than the other two (p less than 0.05); c) 74% of those attended in UH had an evolution of less than 10 years vs 45-58% of the other levels (p less than 0.005); d) no differences were observed in the overall prevalence of complications; e) 37% of the males between 15 and 64 years of age were smokers; f) intensive insulin therapy is more frequently used (p less than 0.05) in DU and UH (56% and 42%) than in EO and CH (19% and 13%); g) the determination of capillary glycemia is generalized (96%); h) 14% had HbA1 or fructosamine lower than the maximum normal value. NIDDM: a) the age of the patients was somewhat lower in DU (59 +/- 11) and UH (58 +/- 11) than in CH (62 +/- 100 and EO (64 +/- 10 (p less than 0.05); b) globally, the rate of insulinization was 55% and home control of glycemia was 43%; c) 47% are hypertense (half of whom are inadequately controlled) and 55% are dyslipemic; d) between 15 and 64 years of age 39% of the males are smokers; e) 27% had HbA1 or fructosamine lower than the maximum normal value. CONCLUSIONS: a) The quality of medical care to diabetics in the centers analyzed is high; b) there is no "patient-type" for level of health care; c) there seems to be more therapeutic "aggressivity" among the health care workers responsible for diabetics in relation to the glucose vs other risk factors.

Prevalence of islet cell antibodies, insulin antibodies and hyperglycaemia in 2291 schoolchildren.

Islet cell antibodies, insulin antibodies and hyperglycaemia were investigated in 2291 healthy schoolchildren. Eight of the subjects had islet cell antibodies and eight had insulin antibodies. However, no schoolchild who was positive for islet cell antibodies also had insulin antibodies present. Hyperglycaemia was observed in five children but neither islet cell antibodies nor insulin antibodies could be detected in the sera from these particular subjects.

Nocturnal insulin and C-peptide rhythms in normal subjects.

Immunoreactive insulin and C-peptide reactive plasma levels in venous blood were studied between 0100 and 0820 h in 10 healthy volunteers to assess nocturnal endogenous insulin secretion and its peripheral extraction. Insulin secretion appeared significantly reduced after 0600 h. No correlations were observed between counterregulatory hormones and insulin secretion during this period. Plasma glucose remained stable throughout the study. An increased peripheral sensitivity to insulin after 0600 h is suggested to explain reduced secretion of insulin.