Complete mitochondrial DNA profile in stroke: A geographical matched case-control study in Spanish population.

INTRODUCTION: Stroke, the second leading cause of death worldwide, is a complex disease influenced by many risk factors among which we can find reactive oxygen species (ROS). Since mitochondria are the main producers of cellular ROS, nowadays studies are trying to elucidate the role of these organelles and its DNA (mtDNA) variation in stroke risk. The aim of the present study was to perform a comprehensive evaluation of the association between mtDNA mutations and mtDNA content and stroke risk. MATERIAL AND METHODS: Homoplasmic and heteroplasmic mutations of the mtDNA were analysed in a case-controls study using 110 S cases and their corresponding control individuals. Mitochondrial DNA copy number (mtDNA-CN) was analysed in 73 of those case-control pairs. RESULTS: Our results suggest that haplogroup V, specifically variants m.72C > T, m.4580G > A, m.15904C > T and m.16298 T > C have a protective role in relation to stroke risk. On the contrary, variants m.73A > G, m.11719G > A and m.14766C > T appear to be genetic risk factors for stroke. In this study, we found no statistically significant association between stroke risk and mitochondrial DNA copy number. CONCLUSIONS: These results demonstrate the possible role of mtDNA genetics on the pathogenesis of stroke, probably through alterations in mitochondrial ROS production.

Selective reduction of nitroarenes using Ru/C and CaH2.

Herein, we report an efficient and highly selective method for the reduction of aromatic, heteroaromatic and halonitro compounds using the readily available and cost-effective Ru/C as a catalyst along with unconventional CaH2 as a source of hydride. In most cases the corresponding anilines can be obtained by simple filtration without further purification. The use of 2-MeTHF and the simple operational work-up constitute a valid alternative to previous methodologies.

Genetic, environmental and life-style factors associated with longevity. Protocol and response of the LONGECYL Study.

OBJECTIVE: To describe the objectives, the methodological approach, the response rate of the Genetic, Environmental and Life-style Factors Study in Castilla y León (Spain). METHOD: The Health Sentinel Network studied a sample of long-lived individuals aged 95 or more (LLI). The study included biological samples processed with the Global Screening Array v3.0 that contains a total of 730,059 markers. Written consent was obtained before the examination. CONCLUSIONS: The LLI contacted were 944, and 760 were completed studied. The 87.4% of LLI were born in Castile and Leon and only 1% were non-native of Spain. Severe cognitive impairment was declared in 8.1% of men and 19.2% of women. Genotyping was performed in 739 LLI, the 78.3% of the contacted sample. Family doctors and nurses achieve high participation in population-based studies. DNA samples were taken from 94% of fully studied LLI, and 100% of these samples where successfully genotyped.

Exercise interventions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

AIMS: To assess the potential multi-domain benefits of exercise interventions on patients with Alzheimer's disease (AD), as well as to determine the specific effects of different exercise modalities (aerobic, strength, or combined training). METHODS: A systematic search was conducted in PubMed and Web of Science until March 2021 for randomized controlled trials assessing the effect of exercise interventions (compared with no exercise) on patients with AD. Outcomes included cognitive function (mini-mental state examination [MMSE] test), physical function (e.g., 6-minute walking test [6MWT]), functional independence (Barthel index), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). A random-effects meta-analysis was conducted. RESULTS: 28 studies (total n = 1337 participants, average age 79-90 years) were included in the systematic review, of which 21 could be meta-analyzed. Although considerable heterogeneity was found, exercise interventions induced several significant benefits, including in Barthel index (n = 147 patients, mean difference [MD]=8.36 points, 95% confidence interval [CI]=0.63-16.09), 6MWT (n = 369, MD=84 m, 95% CI=44-133)), and NPI (n = 263, MD=-4.4 points, 95% CI=-8.42 to -0.38). Benefits were also found in the MMSE test, albeit significance was only reached for aerobic exercise (n = 187, MD=2.31 points, 95% CI 0.45-4.27). CONCLUSIONS: Exercise interventions appear to exert multi-domain benefits in patients with AD.

Dream engineering: Simulating worlds through sensory stimulation.

We explore the application of a wide range of sensory stimulation technologies to the area of sleep and dream engineering. We begin by emphasizing the causal role of the body in dream generation, and describe a circuitry between the sleeping body and the dreaming mind. We suggest that nearly any sensory stimuli has potential for modulating experience in sleep. Considering other areas that might afford tools for engineering sensory content in simulated worlds, we turn to Virtual Reality (VR). We outline a collection of relevant VR technologies, including devices engineered to stimulate haptic, temperature, vestibular, olfactory, and auditory sensations. We believe these technologies, which have been developed for high mobility and low cost, can be translated to the field of dream engineering. We close by discussing possible future directions in this field and the ethics of a world in which targeted dream direction and sleep manipulation are feasible.

Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18.

BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over 64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.

Evaluating tools to define influenza baseline and threshold values using surveillance data, Egypt, season 2016/17.

BACKGROUND: Establishing influenza thresholds and transmission intensity can help evaluate seasonal changes in influenza severity and potential pandemics. We aimed to evaluate the moving epidemic method (MEM) for calculating influenza thresholds for season 2016/17 in Egypt using four parameters, to identify the most useful parameter. Also to measure the agreement between both the country-specific statistical empirical method and World Health Organization method to MEM for determining the length and intensity level of activity of the influenza season. METHODS: Routinely epidemiological and laboratory data from sentinel surveillance sites for Severe Acute Respiratory Infection (SARI) and influenza-like illness (ILI) were used for calculating thresholds for seasons between 2010/11 and 2015/16 to test 2016/17 season. The parameters calculated were: screened ILI consultation rate × 1000, screened ILI composite parameter, influenza positivity percentage among sampled SARI cases, and influenza positivity percentage among sampled ILI and SARI cases. These parameters assess seasonality and intensity of influenza activity using the three proposed methods (mentioned above). Agreement between the three methods was done using several approaches. RESULTS: The intensity of influenza activity by MEM was lower than the other two methods. Agreement between MEM and each of the other two techniques varied appreciably from good to very good for seasonal duration, and poor to fair for intensity level. In addition, parameters including laboratory data showed a pattern of bi-wave activity; the first wave occurred in winter mostly between epidemiological weeks 39 and 52 and the second occurred in spring mostly between weeks 12 and 17. CONCLUSION: Parameters including laboratory data were more useful in defining seasonality of influenza. Further exploration of the MEM model in future seasons may help to provide a more comprehensive understanding of its use and application.

Use of the moving epidemic method (MEM) to assess national surveillance data for respiratory syncytial virus (RSV) in the Netherlands, 2005 to 2017.

BackgroundTo control respiratory syncytial virus (RSV), which causes acute respiratory infections, data and methods to assess its epidemiology are important.AimWe sought to describe RSV seasonality, affected age groups and RSV-type distribution over 12 consecutive seasons in the Netherlands, as well as to validate the moving epidemic method (MEM) for monitoring RSV epidemics.MethodsWe used 2005-17 laboratory surveillance data and sentinel data. For RSV seasonality evaluation, epidemic thresholds (i) at 1.2% of the cumulative number of RSV-positive patients per season and (ii) at 20 detections per week (for laboratory data) were employed. We also assessed MEM thresholds.ResultsIn laboratory data RSV was reported 25,491 times (no denominator). In sentinel data 5.6% (767/13,577) of specimens tested RSV positive. Over 12 seasons, sentinel data showed percentage increases of RSV positive samples. The average epidemic length was 18.0 weeks (95% confidence intervals (CI): 16.3-19.7) and 16.5 weeks (95% CI: 14.0-18.0) for laboratory and sentinel data, respectively. Epidemics started on average in week 46 (95% CI: 45-48) and 47 (95% CI: 46-49), respectively. The peak was on average in the first week of January in both datasets. MEM showed similar results to the other methods. RSV incidence was highest in youngest (0-1 and >1-2 years) and oldest (>65-75 and > 75 years) age groups, with age distribution remaining stable over time. RSV-type dominance alternated every one or two seasons.ConclusionsOur findings provide baseline information for immunisation advisory groups. The possibility of employing MEM to monitor RSV epidemics allows prospective, nearly real-time use of surveillance data.

Influenza surveillance: determining the epidemic threshold for influenza by using the Moving Epidemic Method (MEM), Montenegro, 2010/11 to 2017/18 influenza seasons.

BACKGROUND: In 2009, an improved influenza surveillance system was implemented and weekly reporting to the World Health Organization on influenza-like illness (ILI) began. The goals of the surveillance system are to monitor and analyse the intensity of influenza activity, to provide timely information about circulating strains and to help in establishing preventive and control measures. In addition, the system is useful for comparative analysis of influenza data from Montenegro with other countries. AIM: We aimed to evaluate the performance and usefulness of the Moving Epidemic Method (MEM), for use in the influenza surveillance system in Montenegro. METHODS: Historical ILI data from 2010/11 to 2017/18 influenza seasons were modelled with MEM. Epidemic threshold for Montenegro 2017/18 season was calculated using incidence rates from 2010/11-2016/17 influenza seasons. RESULTS: Pre-epidemic ILI threshold per 100,000 population was 19.23, while the post-epidemic threshold was 17.55. Using MEM, we identified an epidemic of 10 weeks' duration. The sensitivity of the MEM epidemic threshold in Montenegro was 89% and the warning signal specificity was 99%. CONCLUSIONS: Our study marks the first attempt to determine the pre/post-epidemic threshold values for the epidemic period in Montenegro. The findings will allow a more detailed examination of the influenza-related epidemiological situation, timely detection of epidemic and contribute to the development of more efficient measures for disease prevention and control aimed at reducing the influenza-associated morbidity and mortality.

Involvement of mitochondrial haplogroups in myocardial infarction and stroke: A case-control study in Castile and Leon (Spain) population.

There are strong evidences that common mitochondrial DNA (mtDNA) haplogroups may influence the pathogenesis of cardiovascular diseases (CVDs). In this matched case-control study, we investigate the association between mtDNA haplogroups and two CVDs, myocardial infarction (MI) and stroke, and classical cardiovascular risk factors. Data obtained show that haplogroup H constitute a susceptibility risk factor for MI (p=0.001; OR=2.379, 95% CI [1.440-3.990]). Otherwise, our data also suggest a beneficial role of haplogroup J against hypertension (p=0.019; OR=0.348, 95% CI [0.144-0.840]). These results may provide some guidance for predicting the genetic risk of these diseases in different human populations through the differences in energy efficiency between haplogroups.

Diarrea poscolecistectomía: ¿un problema frecuente? / Postcholecystectomy diarrhea is a frequent problem?

Resumen Introducción: La colecistectomía laparoscópica es una de las intervenciones quirúrgicas más frecuentes en nuestro país. La diarrea poscolecistectomía es una entidad poco reconocida, con una prevalencia descrita entre el 0,9 y 35,6%, sin embargo, en Chile esto no ha sido claramente definido. Objetivo: Determinar la prevalencia y características de la diarrea poscolecistectomía laparoscópica electiva en una muestra de pacientes chilenos. Material y métodos: Se aplicó una encuesta telefónica estructurada sobre consistencia y frecuencia de deposiciones, entre 4 y 6 meses después de la intervención, a los pacientes adultos operados de colecistectomía laparoscópica electivamente entre diciembre de 2014 y marzo de 2015. Se definió como «diarrea poscolecistectomía¼ la presencia de deposiciones líquidas o inusualmente disgregadas que hubiesen comenzado posteriormente a la intervención y se estableció el término de «diarrea prolongada¼ como la duración de síntomas mayor de 4 semanas. Resultados: Se encuestó a 100 pacientes (73% de mujeres). La prevalencia global de diarrea poscolecistectomía fue del 35% (n = 35). La prevalencia de pacientes con diarrea prolongada fue del 15% (n = 15). En el grupo con diarrea prolongada, se observó resolución completa de esta en el 57% de los pacientes (n = 8) en un plazo medio de 99 ± 29 días. Conclusión: La diarrea poscolecistectomía es una entidad frecuente en nuestra población, con una alta prevalencia dentro de los primeros 28 días posteriores a la intervención. En la mayoría de los pacientes se resuelve en los primeros 6 meses.

Abstract Introduction: Laparoscopic cholecystectomy (LC) is one of the most common surgical procedures in our country. Postcholecystectomy diarrhea is an unrecognized entity, with a reported prevalence between 0.9 and 35.6%, nonetheless in Chile this has not been clearly defined. Objective: To determine the prevalence and characteristics of diarrhea following elective laparoscopic cholecystectomy in our institution. Material and methods: A structured questionnaire about consistency and defecation frequency was applied to adult patients summited to an elective LC between December 2014 and February 2015, by a telephone survey within 4 and 6 months after the surgical procedure. Postcholecystectomy diarrhea was defined as the presence of liquid or unusually disrupted faecal material beginning after LC. Persistent diarrhea was established when diarrhea continued for a period longer than four weeks. Results: One hundred patients were included (73% women). The overall prevalence of postcholecystectomy diarrhea was 35% (n = 35). The prevalence of patients with persistent diarrhea was 15% (n = 15). In the group of patients with persistent diarrhea, complete resolution was observed on 57% of the cases (n = 8) within an average period of 99 ± 29 days. Conclusion: Post cholecystectomy diarrhea is a frequent condition in our population, with a high prevalence within the first 28 days after LC. In most patients it resolved within 6 months.

Waning protection of influenza vaccine against mild laboratory confirmed influenza A(H3N2) and B in Spain, season 2014-15.

INTRODUCTION: The 2014/15 influenza season in Spain was dominated by the circulation of drifted A(H3N2) and co-circulation of B viruses. We present the final estimates of influenza vaccine effectiveness (IVE) against confirmed influenza A(H3N2) and B its evolution along the season and with time since vaccination. METHODS: We used data collected on influenza like illness patients (ILI), systematically swabbed for the presence of influenza viruses within the Spanish Influenza Sentinel Surveillance System (SISS) and a restricted observational study (cycEVA). We used a test negative case-control design to compare influenza confirmed cases with negative controls. We estimated the IVE through a logistic regression model adjusting for potential confounders. The evolution of IVE was studied in early and late stages of the epidemic, and in different time intervals between receiving influenza vaccination and the onset of symptoms. RESULTS: At the end of the season we have found low and moderate IVE point estimates against influenza A(H3N2) and B, respectively, in all ages and target groups for vaccination. An IVE decreased from an early value of 37% to a late of -76% against influenza A(H3N2), and similarly, 84% vs -4% against Influenza B. When the onset of symptoms occurred more than three months after vaccination, the decrease of IVE was slower and milder against influenza B than against influenza A(H3N2). No significant change in the percentage of circulating drifted influenza A(H3N2) strains belonging to the 3c.2a and 3c.3a clades could be identified through the season. CONCLUSIONS: In a season dominated by drifted A(H3N2) circulating virus, the vaccine offered little or no protection against A(H3N2) infection but had a moderate protective effect against influenza B. Efforts should be put in developing influenza vaccines that maintain their protective capabilities throughout the season and could stimulate a potentially broad immune response against diverse influenza strains.

Influenza surveillance in Europe: comparing intensity levels calculated using the moving epidemic method.

OBJECTIVES: Although influenza-like illnesses (ILI) and acute respiratory illnesses (ARI) surveillance are well established in Europe, the comparability of intensity among countries and seasons remains an unresolved challenge. The objective is to compare the intensity of ILI and ARI in some European countries. DESIGN AND SETTING: Weekly ILI and ARI incidence rates and proportion of primary care consultations were modeled in 28 countries for the 1996/1997-2013/2014 seasons using the moving epidemic method (MEM). We calculated the epidemic threshold and three intensity thresholds, which delimit five intensity levels: baseline, low, medium, high, and very high. The intensity of 2013/2014 season is described and compared by country. RESULTS: The lowest ILI epidemic thresholds appeared in Sweden and Estonia (below 10 cases per 100 000) and the highest in Belgium, Denmark, Hungary, Poland, Serbia, and Slovakia (above 100 per 100 000). The 2009/2010 season was the most intense, with 35% of the countries showing high or very high intensity levels. The European epidemic period in season 2013/2014 started in January 2014 in Spain, Poland, and Greece. The intensity was between low and medium and only Greece reached the high intensity level, in weeks 7 to 9/2014. Some countries remained at the baseline level throughout the entire surveillance period. CONCLUSIONS: Epidemic and intensity thresholds varied by country. Influenza-like illnesses and ARI levels normalized by MEM in 2013/2014 showed that the intensity of the season in Europe was between low and medium in most of the countries. Comparing intensity among seasons or countries is essential for understanding patterns in seasonal epidemics. An automated standardized model for comparison should be implemented at national and international levels.

Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period.

Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009-2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30-64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30-64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.

Age and sex differences in the incidence of diabetes mellitus in a population-based Spanish cohort.

BACKGROUND: The prevalence of diabetes mellitus (DM) in Spain ranges between 10% and 20%. However, very little is known about the incidence of DM because of difficulties involved in estimating it and its apparent lack of usefulness in practice. The aim of the present study was to describe the incidence of type 1 and type 2 DM (T1DM and T2DM, respectively) in the Castilla y León diabetes cohort (CODICyL). METHODS: New diabetes cases, were registered on a standard form that included diagnostic criteria, background, symptoms, results of clinical examination, complications, other cardiovascular risk factors, and treatment. There were 1 354 619 person-years monitored between 2000 and 2013. We estimated the incidence of DM and calculated the relative risks adjusted for age, gender, and year of diagnosis with Poisson regression models. RESULTS: The incidence of DM in individuals aged ≥15 years was 196.9 per 100 000 person-years (95% confidence interval [CI] 188.4-205.7), whereas in those aged <15 years the incidence was 10.8 per 100 000 person-years (95% CI 7.8-14.8). Men had a 36% higher risk than women of developing T2DM (95% CI 25%-49%). The greatest incidence of T2DM was found in 55-64-year-old men and 65-69-year-old women. CONCLUSIONS: The annual incidence of T2DM is approximately 2 per 1000 person-years, higher in men, and peaks in middle age. Although specific tests to differentiate between the two types of DM are not available in this study, the estimation of incidence in those <15 years of age (10.8 per 100 000 person-years) represents a close approximation of the incidence of T1DM.

Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

INTRODUCTION AND OBJECTIVES: There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. METHODS: We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. RESULTS: A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. CONCLUSIONS: There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination.

BACKGROUND: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. METHODS: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. RESULTS: The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0-69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. CONCLUSIONS: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season.

Influenza surveillance in Europe: establishing epidemic thresholds by the moving epidemic method.

BACKGROUND: Timely influenza surveillance is important to monitor influenza epidemics. OBJECTIVES: (i) To calculate the epidemic threshold for influenza-like illness (ILI) and acute respiratory infections (ARI) in 19 countries, as well as the thresholds for different levels of intensity. (ii) To evaluate the performance of these thresholds. METHODS: The moving epidemic method (MEM) has been developed to determine the baseline influenza activity and an epidemic threshold. False alerts, detection lags and timeliness of the detection of epidemics were calculated. The performance was evaluated using a cross-validation procedure. RESULTS: The overall sensitivity of the MEM threshold was 71·8% and the specificity was 95·5%. The median of the timeliness was 1 week (range: 0-4·5). CONCLUSIONS: The method produced a robust and specific signal to detect influenza epidemics. The good balance between the sensitivity and specificity of the epidemic threshold to detect seasonal epidemics and avoid false alerts has advantages for public health purposes. This method may serve as standard to define the start of the annual influenza epidemic in countries in Europe.

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naive B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.