Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1ß and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106.

Drinking and laboratory biomarkers, and nutritional status characterize the clinical presentation of early-stage alcohol-associated liver disease.

Chronic and heavy alcohol consumption is commonly observed in alcohol use disorder (AUD). AUD often leads to alcohol-associated organ injury, including alcohol-associated liver disease (ALD). Approximately 10-20% of patients with AUD progress to ALD. Progression of ALD from the development phase to more advanced states involve the interplay of several pathways, including nutritional alterations. Multiple pathologic processes have been identified in the progression and severity of ALD. However, there are major gaps in the characterization and understanding of the clinical presentation of early-stage ALD as assessed by clinical markers and laboratory measures. Several Institutions and Universities, including the University of Louisville, in collaboration with the National Institutes of Health, have published a series of manuscripts describing early-stage ALD over the past decade. Here, we comprehensively describe early-stage ALD using the liver injury and drinking history markers, and the laboratory biomarkers (with a focus on nutrition status) that are uniquely involved in the development and progression of early-stage ALD.

Characterization of Hypomagnesemia in Alcoholic Hepatitis Patients and Its Association with Liver Injury and Severity Markers.

INTRODUCTION: Hypomagnesemia has been documented in alcohol-associated liver disease (ALD). This study aims to characterize hypomagnesemia in alcoholic hepatitis (AH) patients and identify its response with liver injury and severity markers. MATERIALS AND METHODS: A total of 49 male and female AH patients with an age range of 27-66 years were enrolled in this study. Patients were grouped by MELD: MiAH (mild AH < 12 [n = 5]), MoAH (12 ≤ moderate AH ≤ 19 [n = 13]), and SAH (severe AH ≥ 20 [n = 31]). Patients were also evaluated by MELD grouping as non-severe (MELD ≤ 19 [n = 18]) and severe (MELD ≥ 20 [n = 31]). Data were collected on demographics (Age; BMI), drinking history (AUDIT; LTDH), liver injury (ALT; AST), and liver severity (Maddrey's DF; MELD; AST:ALT). Serum magnesium (SMg) levels were tested as SOC lab (normal ≥ 0.85 ≤ 1.10 mmol/L). RESULTS: SMg was deficient in each group; the lowest in the MoAH patients. The true positivity of SMg values were at a good performance level when compared between severe and non-severe AH patients (AUROC: 0.695, p = 0.034). We found that the SMg level < 0.78 mmol/L could predict severe AH (sensitivity = 0.100 and 1-specificity = 0.000) at this true positivity, and subsequently analyzed patients with SMg < 0.78 mmol/L (Gr.4) and ≥0.78 mmol/L (Gr.5). Between Gr.4 and Gr.5, there were clinically as well as statistically significant differences in disease severity as defined by MELD, Maddrey's DF, and ABIC scores. CONCLUSIONS: This study demonstrates the utility of SMg levels to identify AH patients who may have progressed to severe status. The extent of magnesium response in AH patients also corresponded significantly with the prognosis of liver disease. Physicians suspecting AH in patients with recent heavy drinking may use SMg as an indicator to guide further testing, referrals, or treatment.

One-month assessment of Th-cell axis related inflammatory cytokines, IL-17 and IL-22 and their role in alcohol-associated liver disease.

Introduction: Changes in the expression of cyto- and chemokines due to alcohol-associated liver disease (ALD) have been reported to be both protective and pathogenic. This study examined plasma levels of two key cytokines, Il-17 and Il-22, which construct the proinflammatory vs. anti-inflammatory axes across the spectrum of alcohol use disorder (AUD) and ALD including alcohol-associated hepatitis (AH) to determine the underlying status of the inflammation. Methods: Forty-two males and females aged 25-63 yrs. were grouped as healthy controls (HV[n=8]), AUD with no liver injury (AUDNLI [n=8]), AUD with liver injury (AUDLI [n=8]), non-severe alcohol-associated hepatitis (NSAH [n=9]), and severe alcohol-associated hepatitis (SAH [n=9]). Demographic, drinking, and clinical data were collected. Blood samples were collected at baseline (BL, all subjects) and during week 4 (W4, only patients) for IL-17 and IL-22; and statistically analyzed. Results: IL-17 was highly elevated in the SAH group both at BL and post-SOC. LTDH and BL IL-22 in non-severe AH patients were associated significantly. LTDH significantly predicted W4 IL-22 levels, positively (increasing) in NSAH and inversely (lowering) in SAH patients. BL and W4 IL-22 levels were significantly higher (4-fold, p≤0.001) in all AH patients compared to all AUD patients (AUROC=0.988, p≤0.001). IL-22 showed significant affinity with AST, AST: ALT ratio, total bilirubin, INR, and PT both at BL and W4. IL-22 was inversely associated with IL-1ß; and positively with TNF-α and IL-8 both at BL, and W4. BL IL-17 showed a positive correlation with MELD (p=0.017) in all AH patients. In SAH, > 2-fold W4 IL-17 level compared to BL showed significant within subjects' effects, p=0.006. In AUD patients without AH, the drop in IL-17 at W4 vs. BL showed a significant within subjects' effect, p=0.031. Discussion: Drinking chronicity predicted opposite effects in IL-22 levels in NSAH (antiinflammatory) and SAH (pro-inflammatory) patients at post-SOC. BL IL-22 levels differentiated AH patients robustly from the AUD patients (with or without liver injury); and showed corresponding increases stepwise with the stages of ALD. IL-22 was closely associated with progression and injury markers of the liver; and response to the cytokines of pro-inflammatory nature. Pro-inflammatory indicator of IL-17 cell axis, IL-17 showed a strong positive association with MELD, a severity indicator of AH.

Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function.

(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 ≤ TSH ≤ 3 mIU/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH > 3 mIU/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 ß, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut-immune-thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut-thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p < 0.001) and TNF-α (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut-brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD.

Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients.

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients were sub-divided within each group into patients with normal magnesium (0.85 and more mmol/L) and deficient magnesium (less than 0.85 mmol/L) levels. All participants were assessed at baseline (BL) and received standard medical management for 2 weeks with reassessment at the treatment end (2w). (3) Female participants of this study showed a significantly lower baseline level of magnesium than their male counterparts. Gr.2 patients showed a greater propensity in the necrotic type of liver cell death, who reported higher chronic and recent heavy drinking. Magnesium level improved to the normal range in Gr.2 post-treatment, especially in the hypomagnesemia sub-group (0.77 ± 0.06 mmol/L (BL) vs. 0.85 ± 0.05 mmol/L (2w), p = 0.02). In Gr.2, both apoptotic (K18M30) and necrotic (K18M65) responses were significantly and independently associated with inflammasome activity comprising of LBP (Lipopolysaccharide binding-protein) and TNFα (Tumor necrosis factor -α), along with serum magnesium. (4) In AUD patients with liver injury, 2-week medical management seems to improve magnesium to a normal level. This group exhibited inflammatory activity (LBP and TNFα) contributing to clinically significant hypomagnesemia. In this group, the level of magnesium, along with the unique inflammatory activity, seems to significantly predict apoptotic and necrotic types of hepatocyte death.

Calf- and herd-level factors associated with dairy calf reactivity.

A positive relationship between handlers and animals in farm systems is essential because the human-animal relationship has implications for welfare and productivity. For this reason, on-farm animal welfare assessment protocols often include the behavioral response of animals to humans to measure the quality of the human-animal relationship. The existing literature has described this relationship as being multifactorial in nature. In the current study, we aimed to investigate the potential influence of farm management and infrastructure characteristics, calf manager traits, and intrinsic features of dairy calves on the human-animal relationship. To this end, an escape test was conducted with 698 calves on 30 dairy farms in Chile. This test measured the calf's response to the active approach of an unfamiliar human (and was scored from 0 [fearful] to 4 [friendly]). The explanatory variables used to predict calves' response in the escape test were grouped according to the following categories: (1) farm management and infrastructure (e.g., calf-dam separation age, space allowance); (2) calf manager (e.g., attitudes, behavior, and background); and (3) calf (e.g., breed, sex, age). We concluded that calf managers with additional jobs on the farm, no training, low job satisfaction, a greater proportion of negative contacts, and more negative attitudes were predictive of fearfulness in the escape test. Holstein breed (compared with Holstein and Jersey crossbreeds) was associated with greater odds of fearful calves. Our study confirms the association between animals' fear and handlers' features, which can potentially be used to select employees on a farm. Understanding the factors that influence fear responses in calves may highlight ways to improve the relationship between animals and humans.

Dissemination of thermodynamic temperature above the freezing point of silver.

The mise-en-pratique for the definition of the kelvin at high temperatures will formally allow dissemination of thermodynamic temperature either directly or mediated through high-temperature fixed points (HTFPs). In this paper, these two distinct dissemination methods are evaluated, namely source-based and detector-based. This was achieved by performing two distinct dissemination trials: one based on HTFPs, the other based on absolutely calibrated radiation thermometers or filter radiometers. These trials involved six national metrology institutes in Europe in the frame of the European Metrology Research Programme joint project 'Implementing the new kelvin' (InK). The results have shown that both dissemination routes are possible, with similar standard uncertainties of 1-2 K, over the range 1273-2773 K, showing that, depending on the facilities available in the laboratory, it will soon be possible to disseminate thermodynamic temperatures above 1273 K to users by either of the two methods with uncertainties comparable to the current temperature scale.

[Classification and characteristics of interval cancers in the Principality of Asturias's Breast Cancer Screening Program]. / Clasificación y características del cáncer de intervalo en el programa de detección precoz de cáncer de mama en el Principado de Asturias.

OBJECTIVE: To review and classify the interval cancers found in the Principality of Asturias's Breast Cancer Screening Program (PDPCM). A secondary objective was to determine the histological characteristics, size, and stage of the interval cancers at the time of diagnosis. MATERIAL AND METHODS: We included the interval cancers in the PDPCM in the period 2003-2007. Interval cancers were classified according to the breast cancer screening program protocol, with double reading without consensus, without blinding, with arbitration. Mammograms were interpreted by 10 radiologists in the PDPCM. RESULTS: A total of 33.7% of the interval cancers could not be classified; of the interval cancers that could be classified, 40.67% were labeled true interval cancers, 31.4% were labeled false negatives on screening, 23.7% had minimal signs, and 4.23% were considered occult. A total of 70% of the interval cancers were diagnosed in the year of the period between screening examinations and 71.7% were diagnosed after subsequent screening. A total of 76.9% were invasive ductal carcinomas, 61.1% were stage II when detected, and 78.7% were larger than 10mm when detected. CONCLUSIONS: The rate of interval cancers and the rate of false negatives in the PDPCM are higher than those recommended in the European guidelines. Interval cancers are diagnosed later than the tumors detected at screening. Studying interval cancers provides significant training for the radiologists in the PDPCM.

Validación de la versión española de la escala QoL-AD en pacientes con enfermedad de Alzheimer, cuidadores y profesionales sanitarios / Validation of the Spanish version of the QoL-AD Scale in alzheimer disease patients, their carers, and health professionals

Background: Quality of life (QOL) is becoming increasingly important to measure the effect of interventions on the life of patients with Alzheimer's disease (AD), particularly on the most meaningful issues. However, most of the instruments used to measure QOL have not been validated in the Spanish population. The aim of this study was to determine the psychometric properties of a Spanish version of QoL Scale in patients with AD, carers and health professionals. Material and methods: On hundred and two patients, their carers and 25 health professionals were recruited from day centres. Patients’ QOL was rated by patients, carers and health professionals. The Health Utilities Index, Clinical Insight Rating Scale and Mini Mental State Examination were also administered. Results: The internal and external reliability of QoL-AD were excellent. Criterion validity was indicated by a significant correlation of QoL-AD scores with HUI-3 and QoL-AD global item scores (p<.05). Lack of insight and cognitive impairment did not have an effect on these properties. QoL-AD scores were not significantly different between groups made according sociodemographic characteristics and cognitive impairment (p>.05). The exploratory factor analysis result revealed a three factor solution, which accounted for 61.3% of variance: health factor, functional status factor, and social relationship-environment factor. Conclusions: QoL-AD Scale has proved to be a valid and reliable instrument to measure QoL of Spanish AD patients with mild-to-moderate cognitive impairment and a wide range of anosognosia (AU)

Introducción: La calidad de vida (CV) está adquiriendo cada vez más relevancia como medida para evaluar los resultados de las distintas intervenciones terapéuticas sobre los pacientes con enfermedad de Alzheimer (EA), dado que contempla aspectos que son especialmente valiosos en su vida diaria. Sin embargo, son escasos los instrumentos para medir la CV que han sido validados en población española. El objetivo de este estudio es explorar las propiedades psicométricas de la escala QoL-AD en pacientes, cuidadores y profesionales sanitarios. Pacientes y métodos: Se seleccionó a 102 pacientes con EA en fase leve-moderada, sus cuidadores y 25 profesionales sanitarios. La CV de los pacientes fue valorada por pacientes, cuidadores y profesionales mediante la escala QoL-AD. Además, se administraron MMSE, escala de valoración de insight clínico (CIR) e índice de utilidades de salud (HUI-3). Resultados: La fiabilidad interna y externa de la escala QoL-AD fueron excelentes. La escala presenta validez de criterio dado que sus puntuaciones correlacionaron con las de HUI-3 y la medida global de CV (p<0,05). La falta de insight y el deterioro cognitivo no tuvieron un efecto sobre estas propiedades. Las puntuaciones en la escala QoL-AD no difirieron entre grupos establecidos según MMSE y factores sociodemográficos (p>0,05). En el análisis factorial se obtuvo una solución de tres factores que explica el 61,3% de la varianza: factor salud, factor estado funcional y factor relaciones sociales-ambiente. Conclusiones: La escala QoL-AD es un instrumento válido y fiable para medir la CV en la pacientes españoles con AD que presenten deterioro cognitivo leve-moderado, sea cual fuese su grado de insight (AU)

[Validation of the Spanish version of the QoL-AD Scale in alzheimer disease patients, their carers, and health professionals]. / Validación de la versión española de la escala QoL-AD en pacientes con enfermedad de Alzheimer, cuidadores y profesionales sanitarios.

BACKGROUND: Quality of life (QOL) is becoming increasingly important to measure the effect of interventions on the life of patients with Alzheimer's disease (AD), particularly on the most meaningful issues. However, most of the instruments used to measure QOL have not been validated in the Spanish population. The aim of this study was to determine the psychometric properties of a Spanish version of QoL Scale in patients with AD, carers and health professionals. MATERIAL AND METHODS: On hundred and two patients, their carers and 25 health professionals were recruited from day centres. Patients' QOL was rated by patients, carers and health professionals. The Health Utilities Index, Clinical Insight Rating Scale and Mini Mental State Examination were also administered. RESULTS: The internal and external reliability of QoL-AD were excellent. Criterion validity was indicated by a significant correlation of QoL-AD scores with HUI-3 and QoL-AD global item scores (p<.05). Lack of insight and cognitive impairment did not have an effect on these properties. QoL-AD scores were not significantly different between groups made according sociodemographic characteristics and cognitive impairment (p>.05). The exploratory factor analysis result revealed a three factor solution, which accounted for 61.3% of variance: health factor, functional status factor, and social relationship-environment factor. CONCLUSIONS: QoL-AD Scale has proved to be a valid and reliable instrument to measure QoL of Spanish AD patients with mild-to-moderate cognitive impairment and a wide range of anosognosia.

[A case of ureteritis in Henoch-Shönlein purpura]. / Ureteritis en el contexto de una púrpura de Schönlein-Henoch.

Henoch-Schönlein purpura (HSP) is a multisystemic disorder mainly affecting the skin, joints, gastrointestinal tract, and kidneys but sometime rare complications that have been reported include urologic manifestations. We report a case of a 63 year old man was admitted to the hospital because a neurologic abnormalities, gastrointestinal blood loss and acute renal failure. One year before HSP was dignosed by percutaneous renal biopsy. A few days later admission the temperature was 38 masculineC and urine cultures yielded Echerichia Coli. An angio-magnetic resonance of the abdomen showed a marked dilatation of the distal left ureter with a level inside. Therapy with corticosteroids improved a clinical features and the usual renal function was recovered.

Ureteritis en el contexto de una púrpura de Schönlein-Henoch / A case of ureteritis in Henoch-Schönlein purpura

La púrpura de Schönlein-Henoch (PSH) es una enfermedad multisistémica que afecta principalmente a la piel, articulaciones, aparato digestivo y riñón, y con escasa frecuencia, se han descrito complicaciones urológicas. Presentamos el caso de un paciente varón de 63 años de edad diagnosticado hacía un año de PSH mediante biopsia renal percutánea, que ingresa en el hospital por presentar alteraciones neurológicas, hemorragia digestiva alta y fracaso renal agudo. A los pocos días de su ingreso, presentó fiebre, aislándose en urocultivo una Echerichia Coli. Se realizó una angio-RNM de abdomen donde se objetivó una dilatación del uréter distal izquierdo con un nivel en su interior, compatible con una ureteritis. Comenzó tratamiento con esteroides, desapareciendo la clínica del paciente y mejorando su función renal hasta normalizarse

Henoch-Schönlein purpura (HSP) is a multisystemic disorder mainly affecting the skin, joints, gastrointestinal tract, and kidneys but sometime rare complications that have been reported include urologic manifestations. We report a case of a 63 year old man was admitted to the hospital because a neurologic abnormalities, gastrointestinal blood loss and acute renal failure. One year before HSP was dignosed by percutaneous renal biopsy. A few days later admission the temperature was 38 ºC and urine cultures yielded Echerichia Coli. An angio-magnetic resonance of the abdomen showed a marked dilatation of the distal left ureter with a level inside. Therapy with corticosteroids improved a clinical features and the usual renal function was recovered

Measles aerosol vaccination.

Measles ranks fifth among the five major childhood conditions which are responsible for 21% of all deaths in low and middle-income countries. Measles immunization is considered the most cost-effective public health intervention in the world. In recent years, there has been a critical need to identify alternative routes of measles immunization, which are rapid, reliable, cost-effective, needle-free, and suitable for use in mass campaigns. Aerosol administration of measles vaccines in mass campaigns was first proposed by Dr. Albert Sabin. We review the different clinical trials that have been conducted using the classic Mexican device as well as issues regarding vaccine strain, presentation, and manufacturer. Results of clinical trials indicate that the method is safe and immunogenic in infants and school age children. The viral inoculum will probably need to be increased when administered to infants. From the logistical point of view, the use of the aerosol method has not been evaluated in routine immunization although feasibility of its routine implementation was proved in mass campaigns in Mexico. Cost savings will probably be demonstrated. As to licensure, its compliance with the appropriate international regulatory requirements for medical aerosol delivery devices is in process.

Insuficiencia cardíaca y disfunción diastólica en pacientes en hemodiálisis: factores asociados / Cardiac failure and diastoli disfunction in hemodialysis patients: associated factors

La prevalencia de insuficiencia cardíaca (ICC) en hemodiálisis (HD) es elevada,se ha relacionado con disfunción sistólica, pero su relación con disfuncióndiastólica (DD) no ha sido estudiada.Objetivos: Analizar la incidencia de ICC en una población prevalente en HD yfactores asociados, incluyendo DD.Pacientes y metodo: 79 pacientes en HD; edad: 48 ± 15 años; tiempo en HD:83 ± 62 meses; 55,7% tenía calcificaciones arteriales (CVP) (series radiológicas)y 26% Cardiopatía isquémica (CIsq). Se recogieron parámetros analíticos y clínicosde riesgo cardiovascular, y mediante ecocardiografía se estudiaron: calcificacionesvalvulares (CV), hipertrofia ventricular izquierda (HVI), dilatación VI, disfunciónsistólica y diastólica (DD). Los pacientes se siguieron prospectivamentedos años, recogiendo: incidencia de CIsq, ICC y mortalidad de origen cardíaco.Resultados: Hallazgos ecocardiográficos más frecuentes: HVI (93%) y DD (relajaciónmiocárdica alterada (RMA): 63,5%). El 38,3% presentó ICC, asociándosea mayor tiempo en HD (130/72 meses), mayores niveles de CaxP (74/65), PTH(677/376), fosfatasa alcalina ósea (27/16), aluminio (35/25) y PA sistólica(145/130 mmHg) (p < 0,05), así como a la presencia de CIsq, CVP, CV, HVI yRMA (p < 0,01). La fracción de eyección era normal en ambos grupos. El estudiode regresión logística identificó como factores predictores de ICC: RMA (OR:9,5), CIsq (OR: 15) y PA sistólica (OR: 2,2).Los pacientes con RMA tenían mayor edad (55/37), más tiempo en HD (76/60meses), CVP y CV (p < 0,001). Edad (OR: 2,13) y CVP (OR: 3,9) se comportaroncomo factores predictores de RMA.Conclusiones: Los pacientes en HD presentan elevada incidencia de ICC. La cardiopatíaisquémica, la DD (relajación ventricular alterada) y la PA sistólica se comportancomo factores predictores de su aparición. La DD tiene muy alta prevalencia,y se relaciona con la edad y con la presencia de CVP

Heart failure (CHF) and diastolic dysfuction (DD) relationship has received poorattention in hemodialysis patients (HD).Objetive: To analyse the incidence of CHF in our HD patients, the relationshipwith DD and impact on mortality.Methods: We studied 79 patients: 48 ± 15 years old, mean time on HD 83 ±63 months. Vascular calcification (PVC) was evaluated by radiologic series(55.7%). We analyzed the presence of clinical and analytical cardiovascular factors.All patients underwent M-mode, two-dimensional, Doppler echocardiography.Patients were followed for two years. Clinical information collected: incidence ofischemic heart disease (IHD), CHF, and mortality due to cardiovascular events.Results: Most frequent finding was Left Ventricular Hypertrophy (LVH) (93%),followed by DD (63.5% had anormal LV relaxation) (ALVR). Incidence of CHFwas 38.3%; and was significantly associated with higher: time on HD (130/72months), Ca x P (74/65), PTH (677/376), bone alkaline phosphatase (27/16), andsystolic BP (145 vs 130 mmHg); IHD, PVC, valvular calcification (VC), LVH andALVR (p < 0.01). Systolic function was normal in both groups (with/without CHF).Logistic regression identified as risk factors for CHF: ALVR (OR: 9.5), IHD (OR:15) and systolic BP (OR: 2.2).ALVR was associated with greater age (55/37), longer time on HD (76/60), PVCand VC (p < 0.001). Predictor factors identified were age (OR: 2.13) and PVC(OR: 3.9).Conclusions: HD patients showed a high incidence of CHF. IHD, systolic BPand DD (ALVR) have behave as risk factors for CHF. Vascular calcifications wereintimately related to these findings and, therefore, they contribute to the greatermortality of these patients

Evolución fatal de un paciente afecto de enfermedad de Fabry en tratamiento enzimático / No disponible

No disponible

The structure of RalF, an ADP-ribosylation factor guanine nucleotide exchange factor from Legionella pneumophila, reveals the presence of a cap over the active site.

The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms a cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the "glutamic finger," conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.

[Cardiac failure and diastolic disfunction in hemodialysis patients: associated factors]. / Insuficiencia cardíaca y disfunción diastólica en pacientes en hemodiálisis: factores asociados.

UNLABELLED: Heart failure (CHF) and diastolic dysfuction (DD) relationship has received poor attention in hemodialysis patients (HD). OBJECTIVE: To analyse the incidence of CHF in our HD patients, the relationship with DD and impact on mortality. METHODS: We studied 79 patients: 48 +/- 15 years old, mean time on HD 83 +/- 63 months. Vascular calcification (PVC) was evaluated by radiologic series (55.7%). We analyzed the presence of clinical and analytical cardiovascular factors. All patients underwent M-mode, two-dimensional, Doppler echocardiography. Patients were followed for two years. Clinical information collected: incidence of ischemic heart disease (IHD), CHF, and mortality due to cardiovascular events. RESULTS: Most frequent finding was Left Ventricular Hypertrophy (LVH) (93%), followed by DD (63.5% had anormal LV relaxation) (ALVR). Incidence of CHF was 38.3%; and was significantly associated with higher: time on HD (130/72 months), Ca x P (74/65), PTH (677/376), bone alkaline phosphatase (27/16), and systolic BP (145 vs 130 mmHg); IHD, PVC, valvular calcification (VC), LVH and ALVR (p < 0.01). Systolic function was normal in both groups (with/without CHF). Logistic regression identified as risk factors for CHF: ALVR (OR: 9.5), IHD (OR: 15) and systolic BP (OR: 2.2). ALVR was associated with greater age (55/37), longer time on HD (76/60), PVC and VC (p < 0.001). Predictor factors identified were age (OR: 2.13) and PVC (OR: 3.9). CONCLUSIONS: HD patients showed a high incidence of CHF. IHD, systolic BP and DD (ALVR) have behave as risk factors for CHF. Vascular calcifications were intimately related to these findings and, therefore, they contribute to the greater mortality of these patients.