ABSTRACT
OBJECTIVE: Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. METHODS: We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. RESULTS: In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. INTERPRETATION: This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.
Subject(s)
Compassionate Use Trials/methods , Deoxyribonucleosides/therapeutic use , Muscular Diseases/drug therapy , Muscular Diseases/enzymology , Thymidine Kinase/deficiency , Adult , Child , Child, Preschool , Female , Humans , Male , Walk Test/methodsABSTRACT
Mental health modulates the risk of common chronic conditions. Although inflammation is thought to partly explain this link, its relation with mental health is still unclear and largely unexplored. We investigated three scales assessing psychological resilience (CD-RISC), depression symptoms (PHQ9-6) and mental wellbeing (SF36-MCS) in an Italian adult population cohort (Nmaxâ¯=â¯16,952). This showed a slightly higher frequency of men, more educated and younger participants, compared to samples with incomplete questionnaires. We performed stepwise generalized linear models to test the association between each scale and INFLA-score, a composite blood-based inflammation index. At each step, a class of potential mediators was included in the model, namely health conditions, lifestyle factors, or both (full model). Full model analysis was also conducted on single blood markers involved in the inflammatory process. In the baseline model, we observed significant associations of PHQ9-6 (standardized ß(SE)â¯=â¯0.024(0.009), pâ¯=â¯8.9â¯×â¯10-3) and SF36-MCS (ß(SE)â¯=â¯-0.021(0.008), pâ¯=â¯7â¯×â¯10-3) with INFLA-score. These associations survived adjustment for health conditions but not for lifestyle factors, which explained 81% and 17% of the association with PHQ9-6 and SF36-MCS. Significant associations (pâ¯<â¯4.2â¯×â¯10-3) after mediator adjustment were observed for single low-grade inflammation markers, including platelet distribution width (with PHQ9-6 and CD-RISC), granulocyte- and neutrophil-to-lymphocyte ratios, monocyte and lymphocyte fractions (with SF36-MCS). After imputation of missing data, we observed substantially consistent associations. These findings suggest that the relationship between mental health and low-grade inflammation is largely influenced by lifestyle. However, the associations with specific biomarkers related to inflammation are partly independent and might be explained by biological factors.
Subject(s)
Biological Factors , Mental Health , Adult , Humans , Inflammation , Italy , Life Style , MaleABSTRACT
BACKGROUND: There is poor knowledge on the association between combined lifestyles with mortality risk among individuals at high risk, and little is known on the biological mechanisms that could be on the pathway. METHODS: Longitudinal analysis on 22 839 individuals from the Moli-sani Study (Italy, 2005-2010). Among them, we identified 5200 elderly individuals (≥65 year), 2127 subjects with diabetes and 1180 with cardiovascular disease (CVD) at baseline. A healthy lifestyle score (HLS) was calculated, allocating 1 point for each of the following: abstention from smoking; adherence to Mediterranean diet; physical activity; absence of abdominal obesity. Hazard ratios (HR) with 95% confidence intervals (95%CI) were calculated by multivariable Cox regression and competing risk models. RESULTS: During 8.2 years of follow-up, 1237 deaths occurred. In the general population, adherence to all four healthy lifestyles, compared with none or 1, was associated with lower risk of all-cause (HR = 0.53; 95%CI:0.39-0.72), CVD (HR = 0.54; 0.32-0.91), cancer (HR = 0.62; 0.39-1.00) and mortality from other causes (HR = 0.39; 0.19-0.81). A 1-point increase in HLS was associated with 20%, 22% and 24% lower risk of total mortality among the elderly, in subjects with diabetes or CVD, respectively. Traditional (e.g. blood lipids), inflammatory (e.g. C-reactive protein) and novel biomarkers (e.g. markers of cardiac damage) accounted for up to 24% of the association of HLS with all-cause mortality risk in the general population. CONCLUSIONS: The impact of combined four healthy lifestyles on survival was considerable, both in the general population and among high-risk subgroups. Inflammatory and novel biomarkers of CVD risk explained a substantial proportion of this association.
Subject(s)
Healthy Lifestyle , Mortality/trends , Aged , Biomarkers , Cardiovascular Diseases/mortality , Diabetes Mellitus/mortality , Diet, Mediterranean , Exercise , Female , Humans , Italy , Longitudinal Studies , Male , Obesity , Prospective Studies , Risk Factors , Smoking CessationABSTRACT
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case-control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2-16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015-2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3-54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3-63.6) and 28.8% (95% CI -31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015-2016 and continues to support the rollout of the LAIV childhood programme.
Subject(s)
Hospitalization/statistics & numerical data , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adolescent , Case-Control Studies , Child , Child, Preschool , England , Female , Humans , Male , Treatment Outcome , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunologyABSTRACT
BACKGROUND AND AIMS: Whole grain (WG) food consumption is associated with lower risk of cardiovascular disease, cancer and neurological diseases. The aim of this study was to assess the consumption of WG food and its major demographic, socioeconomic, psychosocial and behavioral determinants in a general Italian population. METHODS AND RESULTS: Data were from the Italian Nutrition & Health Survey (INHES), a telephone-based survey established in 2010-2013 including 9422 participants aged ≥5 years from all over Italy. WG food intake was assessed by the European Food Propensity Questionnaire and included bread, pasta, breakfast cereals, biscuits and WG soups. WG consumption was categorized as none, occasional (<1 time/week) and regular (≥1 time/week). Overall, 26.9% of the sample reported a regular consumption of WG food (27.2% of adults aged 20-97 y, and 21.9% of children/adolescents aged 5-19 y). In both age-groups, the major food source contributing to total WG intake was WG bread followed by WG pasta. Among adults, greater consumption of WG was associated with healthier lifestyle (e.g. sport activity), and higher educational level. Eating meals outside of the house in adults, and spending >2 h/day watching TV in children/adolescents were inversely associated with WG intake. CONCLUSIONS: The percentage of WG consumers in Italy in 2010-2013 appears to be quite low and still below that recorded in other countries of Europe where consumption is frequently over 50 percent. WG consumption is likely to be influenced by socioeconomic status and is associated with a number of psychosocial factors, meal patterns and eating-related behaviors.
Subject(s)
Diet, Healthy , Feeding Behavior , Health Behavior , Meals , Recommended Dietary Allowances , Whole Grains , Adolescent , Adolescent Behavior , Adult , Aged , Aged, 80 and over , Child , Child Behavior , Child, Preschool , Cross-Sectional Studies , Educational Status , Exercise , Female , Humans , Italy , Male , Middle Aged , Nutrition Surveys , Nutritive Value , Screen Time , Time Factors , Young AdultABSTRACT
BACKGROUND AND AIMS: Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults. METHODS AND RESULTS: 19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF. CONCLUSION: Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population.
Subject(s)
Heart Failure/blood , Hospitalization , Vitamin D Deficiency/blood , Vitamin D/analogs & derivatives , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Incidence , Inflammation Mediators/blood , Italy/epidemiology , Male , Middle Aged , Prevalence , Prospective Studies , Registries , Risk Assessment , Risk Factors , Time Factors , Vitamin D/blood , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiologyABSTRACT
We describe the case of a woman in whom combination of a mitochondrial (MT-CYB) and a nuclear (SDHB) mutation was associated with clinical and metabolic features suggestive of a mitochondrial disorder. The mutations impaired overall energy metabolism in the patient's muscle and fibroblasts and increased cellular susceptibility to oxidative stress. To clarify the contribution of each mutation to the phenotype, mutant yeast strains were generated. A significant defect in strains carrying the Sdh2 mutation, either alone or in combination with the cytb variant, was observed. Our data suggest that the SDHB mutation was causative of the mitochondrial disorder in our patient with a possible cumulative contribution of the MT-CYB variant. To our knowledge, this is the first association of bi-genomic variants in the mtDNA and in a nuclear gene encoding a subunit of complex II.
Subject(s)
Mitochondrial Encephalomyopathies/diagnosis , Adenosine Triphosphate/metabolism , Adult , Amino Acid Sequence , Base Sequence , DNA Mutational Analysis , Diagnosis, Differential , Female , Humans , Mitochondrial Encephalomyopathies/genetics , Molecular Diagnostic Techniques , Molecular Sequence Data , Mutation, Missense , Polymorphism, Restriction Fragment Length , Saccharomyces cerevisiaeABSTRACT
Human parainfluenza virus (HPIV) infections are one of the commonest causes of upper and lower respiratory tract infections. In order to determine if there have been any recent changes in HPIV epidemiology in England and Wales, laboratory surveillance data between 1998 and 2013 were analysed. The UK national laboratory surveillance database, LabBase, and the newly established laboratory-based virological surveillance system, the Respiratory DataMart System (RDMS), were used. Descriptive analysis was performed to examine the distribution of cases by year, age, sex and serotype, and to examine the overall temporal trend using the χ 2 test. A random-effects model was also employed to model the number of cases. Sixty-eight per cent of all HPIV detections were due to HPIV type 3 (HPIV-3). HPIV-3 infections were detected all year round but peaked annually between March and June. HPIV-1 and HPIV-2 circulated at lower levels accounting for 20% and 8%, respectively, peaking during the last quarter of the year with a biennial cycle. HPIV-4 was detected in smaller numbers, accounting for only 4% and also mainly observed in the last quarter of the year. However, in recent years, HPIV-4 detection has been reported much more commonly with an increase from 0% in 1998 to 3·7% in 2013. Although an overall higher proportion of HPIV infection was reported in infants (43·0%), a long-term decreasing trend in proportion in infants was observed. An increase was also observed in older age groups. Continuous surveillance will be important in tracking any future changes.
Subject(s)
Paramyxoviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , England/epidemiology , Female , Humans , Infant , Male , Middle Aged , Paramyxoviridae Infections/virology , Prevalence , Respiratory Tract Infections/virology , Seasons , Serogroup , Sex Distribution , Wales/epidemiology , Young AdultABSTRACT
BACKGROUND AND AIMS: Fish consumption reportedly reduces the risk of heart disease, but the evidence of cardiovascular advantages associated with fish intake within Mediterranean cohorts is limited. The aim of this study was to test the association between fish intake and risk of composite coronary heart disease (CHD) and stroke in a large population-based cohort adhering to Mediterranean Diet. METHODS AND RESULTS: Prospective analysis on 20,969 subjects free from cardiovascular disease at baseline, enrolled in the Moli-sani study (2005-2010). Food intake was recorded by the Italian version of the EPIC food frequency questionnaire. Hazard ratios were calculated by using multivariable Cox-proportional hazard models. During a median follow-up of 4.3 years, a total of 352 events occurred (n of CHD = 287 and n of stroke = 66). After adjustment for a large panel of covariates, fish intake ≥4 times per week was associated with 40% reduced risk of composite CHD and stroke (HR = 0.60; 95%CI 0.40-0.90), and with 40% lower risk of CHD (HR = 0.60; 95%CI 0.38-0.94) as compared with subjects in the lowest category of intake (<2 times/week). A similar trend of protection was found for stroke risk although results were not significant (HR = 0.62; 95%CI 0.26-1.51). When fish types were considered, protection against the composite outcome and CHD was confined to fatty fish intake. CONCLUSIONS: Fish intake was associated with reduced risk of composite fatal and non-fatal CHD and stroke in a general Mediterranean population. The favourable association was likely to be driven by fatty fish.
Subject(s)
Coronary Disease/prevention & control , Diet, Healthy , Diet, Mediterranean , Dietary Fats/administration & dosage , Fishes , Seafood , Stroke/prevention & control , Adult , Aged , Animals , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Feeding Behavior , Female , Humans , Italy/epidemiology , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Prospective Studies , Protective Factors , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Time FactorsABSTRACT
BACKGROUND AND AIM: Dietary habits evolve over time, being influenced by many factors and complex interactions. This work aimed at evaluating the updated information on food group consumption in Italy. METHODS AND RESULTS: A total of 8944 (4768 women and 4176 men) participants aged >18 years from all over Italy recruited in 2010-13 (Italian Nutrition & HEalth Survey, INHES) was analyzed. The recruitment was performed using computer-assisted-telephone-interviewing and one-day 24-h dietary recall retrieved from all participants. The updated, second version, of FoodEx2 food classification system was applied to extract data on food group consumption. The participation rate was 53%; 6.2% of the participants declared to follow a special diet, the most prevalent being hypo-caloric diets (55.7% of special diets). Men compared to women presented significantly higher intakes of "grains and grain-based products", "meat and meat products", "animal and vegetable fats and oils and primary derivatives" and "alcoholic beverages" (P for all<0.001); moreover, men had lower intakes of "milk and dairy products", "water and water-based beverages" and "products for non-standard diets, food imitates and food supplements" (P for all<0.001). Differences in food group intake among age groups, geographical regions and educational level groups were also identified (P for all<0.05). CONCLUSIONS: Data on the consumption of more than 70 food groups and sub-groups were illustrated in different strata. The present analysis could be considered as an updated source of information for future nutrition research in Italy and in the EU.
Subject(s)
Diet/classification , Eating , Feeding Behavior/classification , Food/classification , Meals/classification , Adult , Age Distribution , Aged , Educational Status , Female , Humans , Italy , Male , Middle Aged , Nutrition Surveys , Sex DistributionABSTRACT
We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.
Subject(s)
Anemia, Macrocytic/genetics , Membrane Proteins/genetics , Mitochondrial Diseases/genetics , Adolescent , Animals , Child , Erythropoiesis/genetics , Exome , Female , Gene Knockdown Techniques , Humans , Mitochondrial Proteins/genetics , Mutation , Zebrafish/geneticsABSTRACT
The epidemiology of laboratory-confirmed respiratory syncytial virus (RSV) infections in young children has not recently been described in England, and is an essential step in identifying optimal target groups for future licensed RSV vaccines. We used two laboratory surveillance systems to examine the total number and number of positive RSV tests in children aged <5 years in England from 2010 to 2014. We derived odds ratios (ORs) with 95% confidence intervals (CIs) comparing children by birth month, using multivariable logistic regression models adjusted for age, season and sex. Forty-seven percent of RSV tests (29 851/63 827) and 57% (7405/13 034) of positive results in children aged <5 years were in infants aged <6 months. Moreover, 38% (4982/13 034) of positive results were in infants aged <3 months. Infants born in September, October and November had the highest odds of a positive RSV test during their first year of life compared to infants born in January (OR 2·1, 95% CI 1·7-2·7; OR 2·4, 95% CI 2·1-2·8; and OR 2·4, 95% CI 2·1-2·7, respectively). Our results highlight the importance of young age and birth month near the beginning of the RSV season to the risk of laboratory-confirmed RSV infection. Future control measures should consider protection for these groups.
Subject(s)
Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus, Human/isolation & purification , Child, Preschool , England/epidemiology , Female , Humans , Infant , Infant, Newborn , Logistic Models , Male , Odds Ratio , Respiratory Syncytial Virus Infections/virology , SeasonsABSTRACT
A large evidence-based review on the effects of a moderate consumption of beer on human health has been conducted by an international panel of experts who reached a full consensus on the present document. Low-moderate (up to 1 drink per day in women, up to 2 in men), non-bingeing beer consumption, reduces the risk of cardiovascular disease. This effect is similar to that of wine, at comparable alcohol amounts. Epidemiological studies suggest that moderate consumption of either beer or wine may confer greater cardiovascular protection than spirits. Although specific data on beer are not conclusive, observational studies seem to indicate that low-moderate alcohol consumption is associated with a reduced risk of developing neurodegenerative disease. There is no evidence that beer drinking is different from other types of alcoholic beverages in respect to risk for some cancers. Evidence consistently suggests a J-shaped relationship between alcohol consumption (including beer) and all-cause mortality, with lower risk for moderate alcohol consumers than for abstainers or heavy drinkers. Unless they are at high risk for alcohol-related cancers or alcohol dependency, there is no reason to discourage healthy adults who are already regular light-moderate beer consumers from continuing. Consumption of beer, at any dosage, is not recommended for children, adolescents, pregnant women, individuals at risk to develop alcoholism, those with cardiomyopathy, cardiac arrhythmias, depression, liver and pancreatic diseases, or anyone engaged in actions that require concentration, skill or coordination. In conclusion, although heavy and excessive beer consumption exerts deleterious effects on the human body, with increased disease risks on many organs and is associated to significant social problems such as addiction, accidents, violence and crime, data reported in this document show evidence for no harm of moderate beer consumption for major chronic conditions and some benefit against cardiovascular disease.
Subject(s)
Beer , Cardiovascular Diseases/epidemiology , Dementia/epidemiology , Ethanol/administration & dosage , Neoplasms/epidemiology , Polyphenols/administration & dosage , Animals , Beer/adverse effects , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/prevention & control , Cause of Death , Consensus , Dementia/diagnosis , Dementia/mortality , Dementia/prevention & control , Dose-Response Relationship, Drug , Ethanol/adverse effects , Evidence-Based Medicine , Female , Health Status , Humans , Male , Neoplasms/diagnosis , Neoplasms/mortality , Neoplasms/prevention & control , Nutritive Value , Polyphenols/adverse effects , Prognosis , Protective Factors , Risk Assessment , Risk FactorsABSTRACT
AIMS: This study aimed to investigate the prevalence of Simkania negevensis in the chlorinated water of spa swimming pools and domestic network systems. METHODS AND RESULTS: A total of 10 and 36 samples were collected from two domestic water supplies and four spa facilities, respectively. Simkania negevensis was isolated in Acanthamoeba castellanii monolayers and detected by Gimenez staining and immunofluorescence test. Simkania negevensis DNA, extracted from the positive samples, was confirmed by a nested PCR assay followed by sequencing. Simkania negevensis was detected in 41·3% of samples (domestic water: 50%; untreated spa supply water: 25%; chlorinated spa pool water: 42·9%) from all the examined water systems in successive samplings performed in 1 year. The presence of S. negevensis was not correlated with the counts of Heterotrophic Bacteria and Pseudomonas aeruginosa. Unlike Legionella spp., which were never isolated from the swimming-pool water samples, S. negevensis was also detected in chlorinated spa water. CONCLUSIONS: This investigation shows that Simkania is widespread in natural and man-made aquatic environments, which may represent possible sources of infection: in the swimming pools, in particular, the aerosol generated by the water movement could increase the risk of inhalation of infected particles. SIGNIFICANCE AND IMPACT OF THE STUDY: This study represents the first evidence of the presence of S. negevensis in spa pool water. Sero-epidemiological surveys on spa users could help to clarify its transmission in this environment.
Subject(s)
Chlamydiales/isolation & purification , Swimming Pools , Water Microbiology , Water Supply , Halogenation , Water/chemistryABSTRACT
BACKGROUND: Subnational variation of 2009 pandemic influenza activity in England has been reported; however, little work has been published on this topic for seasonal influenza. If variation is present, this knowledge may assist with both identifying the onset of influenza epidemics, informing community antiviral prescription and local health planning. METHODS: An end-of-season analysis of influenza surveillance systems (acute respiratory outbreaks, primary care consultations, virological testing, influenza-confirmed secondary care admissions and excess all-cause mortality) was undertaken at national and subnational levels for 2012/13 when influenza B and A(H3N2) dominated. RESULTS: National community antiviral prescription was recommended in Week 51 following national threshold exceedance. However, this was preceded up to 2 weeks by subnational influenza activity in 2/9 regions in England. Regional variation in circulation of influenza subtypes was observed and severe influenza surveillance data sources were able to monitor the subnational impact. CONCLUSIONS: Evidence of virological activity in two or more regions above a threshold indicated the onset of the 2012/13 season. Subnational thresholds should be determined and evaluated in order to improve timeliness of the national antiviral alert. During the season, outputs should be reported at levels that can inform local public health responses and variation considered when retrospectively evaluating the impact of interventions.
Subject(s)
Antiviral Agents/therapeutic use , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Disease Outbreaks , England/epidemiology , Female , Humans , Male , Population Surveillance , Public HealthABSTRACT
Muir-Torre syndrome (MTS) is an autosomal genodermatosis that is diagnosed by the presence of at least one sebaceous gland tumor and at least one visceral malignancy. The most frequent visceral malignancies reported in literature are low-grade colon-rectal and genitourinary cancers, with prolonged survival. The authors report the case of a 52-year-old female, with a positive familial history for MTS, who developed a cutaneous sebaceous carcinoma, a synchronous colon-rectal adenocarcinoma, and a metachronous endocervical adenocarcinoma associated with a neuroendocrine small cell carcinoma of the cervix (SCNC), with lymph node metastasis. The rare occurrence in literature of the cervical SCNC and the rarest occurrence of a neuroendocrine carcinoma in the context of a MTS deviate from the usual and low-grade types of cancers normally described with MTS. It should be always appropriate to assess any symptoms that might reveal an underlying malignancy, although not within the spectrum of neoplasms most associated with this rare syndrome.
Subject(s)
Adenocarcinoma/pathology , Carcinoma, Neuroendocrine/pathology , Carcinoma, Small Cell/pathology , Muir-Torre Syndrome/complications , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology , Uterine Cervical Neoplasms/pathology , Colorectal Neoplasms/pathology , Female , Humans , Middle AgedABSTRACT
Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism of which less than 20 observations have been described. Patients exhibit urinary excretion of specific N-acetyl amino acids and manifest a heterogeneous clinical spectrum including intellectual disability, motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features. Here, we report the case of ACY1 enzyme deficiency in a 6-year-old girl presenting severe intellectual disability, motor retardation, absence of spontaneous locomotor activity and severe speech delay. Urinary excretion of N-acetylated amino acids was present. Mutational analysis of ACY1 gene identified the new homozygous c.1001_1001+5del6 mutation, which alters the mRNA transcription leading to exon 13 skipping and inclusion of a premature stop codon (p.Lys308Glufs*7). A quantitative fluorescent multiplex-polymerase chain reaction (QFM-PCR) assay has been set up and confirmed homozygosity of the mutation in the patient's DNA. Biochemical analysis showed absence of ACY1 enzyme activity in the patient's fibroblasts. The structure of the mutated protein has been defined by homology modeling (HM). Our data endorse the hypothesis of a link between this inborn error of metabolism and the neurological manifestations observed in patients with ACY1 deficiency.
Subject(s)
Amidohydrolases/deficiency , Amino Acid Metabolism, Inborn Errors/genetics , Exons/genetics , Amidohydrolases/biosynthesis , Amidohydrolases/genetics , Amino Acid Metabolism, Inborn Errors/pathology , Child , Female , Fibroblasts/metabolism , Humans , RNA, Messenger/biosynthesis , RNA, Messenger/geneticsABSTRACT
PURPOSE: The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. METHODS: ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. RESULTS: The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). CONCLUSIONS: Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.
Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Aptamers, Nucleotide/adverse effects , Bevacizumab , Female , Humans , Intravitreal Injections , Macular Degeneration/drug therapy , Male , Ranibizumab , World Health OrganizationABSTRACT
BACKGROUND AND AIMS: Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. METHODS AND RESULTS: Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. CONCLUSION: Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn.
Subject(s)
Diet, Mediterranean/economics , Feeding Behavior , Patient Compliance , Adult , Aged , Cohort Studies , Cross-Sectional Studies , Female , Humans , Italy , Male , Middle Aged , Motor Activity , Multivariate Analysis , Nutritional Status , Regression Analysis , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND AND AIMS: Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. METHODS: In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. RESULTS: Italian cohort showed lower plasma and RBC n-3 levels than participants of the other two populations (P<0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n-3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n-3 variation as compared to vegetable oils and polyphenol-rich foods. CONCLUSION: The Italian cohort presented significant lower plasma and RBC n-3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n-3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.