The GENDER ATTENTION Observational Study: Gender and Hormonal Status Differences in the Incidence of Adverse Events During Cyclosporine Treatment in Psoriatic Patients.

INTRODUCTION: Female sex has been shown to be a risk factor for the development of adverse drug reactions; however, this has not been studied for cyclosporine (CsA). The aim of this study was to investigate, in Italian dermatological practice, the influence of gender and menopause and related hormones on the incidence of adverse events (AEs) during CsA treatment in psoriatic patients. METHODS: Multicenter, prospective, observational study conducted from May 2011 to June 2013. Patients with plaque psoriasis, undergoing a new CsA administration course, or about to start it, were enrolled in the outpatient clinics of Italian dermatological centers. During the 2-6 months of study duration, patients had to note all AEs that occurred in a diary that was reviewed by the investigators at the follow-up visit. Sex hormone levels were measured within 7 days from the start date of a menstrual cycle. RESULTS: A total of 969 adult psoriatic patients were enrolled in the study, divided into four cohorts: fertile women and corresponding age-matched men; postmenopausal women and corresponding age-matched men. A significant difference in the percentage of patients with AEs was observed between fertile and postmenopausal women, but not between women and age-matched men. AE incidence rate was about 37% higher in fertile women than in age-matched men and about 18% higher in postmenopausal women than in age-matched men, but differences were not statistically significant. Incidence rate ratio of fertile vs. postmenopausal women was 0.67, reaching statistical significance. AEs were mild or moderate in severity in the great majority of patients of all cohorts and postmenopausal women had significantly less grade 1-2 AEs compared to fertile women, but more grade 3-4 AEs. FSH levels were significantly higher in postmenopausal women reporting no AEs, and DHEA sulfate levels were about 10% higher in men with no AEs, compared to those reporting at least one AE. Cortisol levels were slightly though significantly higher in postmenopausal women with no AE. CONCLUSIONS: A better understanding of sex- and hormone-related influences on drug responses may help to improve drug safety and efficacy, by permitting one to tailor pharmacological treatments to individual subjects or defined patient cohorts. FUNDING: Novartis Farma S.p.A., Italy.

On the role of ethylene, auxin and a GOLVEN-like peptide hormone in the regulation of peach ripening.

BACKGROUND: In melting flesh peaches, auxin is necessary for system-2 ethylene synthesis and a cross-talk between ethylene and auxin occurs during the ripening process. To elucidate this interaction at the transition from maturation to ripening and the accompanying switch from system-1 to system-2 ethylene biosynthesis, fruits of melting flesh and stony hard genotypes, the latter unable to produce system-2 ethylene because of insufficient amount of auxin at ripening, were treated with auxin, ethylene and with 1-methylcyclopropene (1-MCP), known to block ethylene receptors. The effects of the treatments on the different genotypes were monitored by hormone quantifications and transcription profiling. RESULTS: In melting flesh fruit, 1-MCP responses differed according to the ripening stage. Unexpectedly, 1-MCP induced genes also up-regulated by ripening, ethylene and auxin, as CTG134, similar to GOLVEN (GLV) peptides, and repressed genes also down-regulated by ripening, ethylene and auxin, as CTG85, a calcineurin B-like protein. The nature and transcriptional response of CTG134 led to discover a rise in free auxin in 1-MCP treated fruit. This increase was supported by the induced transcription of CTG475, an IAA-amino acid hydrolase. A melting flesh and a stony hard genotype, differing for their ability to synthetize auxin and ethylene amounts at ripening, were used to study the fine temporal regulation and auxin responsiveness of genes involved in the process. Transcriptional waves showed a tight interdependence between auxin and ethylene actions with the former possibly enhanced by the GLV CTG134. The expression of genes involved in the regulation of ripening, among which are several transcription factors, was similar in the two genotypes or could be rescued by auxin application in the stony hard. Only GLV CTG134 expression could not be rescued by exogenous auxin. CONCLUSIONS: 1-MCP treatment of peach fruit is ineffective in delaying ripening because it stimulates an increase in free auxin. As a consequence, a burst in ethylene production speeding up ripening occurs. Based on a network of gene transcriptional regulations, a model in which appropriate level of CTG134 peptide hormone might be necessary to allow the correct balance between auxin and ethylene for peach ripening to occur is proposed.

[Considerations on what we can (and what we should not) ask to registries]. / Riflessioni e confronti su cosa possiamo (e cosa non dobbiamo) chiedere ai registri.

This article presents a summary of the discussion which took place during the works of PRIER II in the session dedicated to the methodology of registries. Following a thorough analysis of the possible methods and the limits which deal with the collection of clinical data through the registries, the different points of view were compared, perhaps the most relevant, related to this activity. All this has been done by taking advantage by the possibility to observe aspects from different points of view. In particular, the exercise considered those who have to deal with the methodological aspects of the registries as an operator of public health or as a private operator who creates services for companies. The final goal, again, was to line up a few essential points accompanied by reasoning and comments useful to anyone who wants to address the issue of registries from the methodological point of view.

Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort.

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

Puberty in modernizing Kazakhstan: a comparison of rural and urban children.

BACKGROUND: Data on puberty development are available for several countries but not for Central Asia. AIM: Using data collected during the Kazakhstan Health and Nutrition Survey (KHA-ES), we evaluated the relationship between the living environment (rural vs. urban), ethnicity (Russians vs. Kazakhs) and pubertal status in children living in Kazakhstan. SUBJECTS AND METHODS: Genital (G1-G5), breast (B1-B5) and pubic hair (PH1-PH5) development were evaluated in a sample of 2389 boys and 2416 girls using Tanner's criteria. Age at menarche was evaluated using the 'status quo' and 'recall' methods. RESULTS: Rural children were older than urban children at stages > or =G2 for males and > or =B2 for females, and this difference was more evident for Russian males. Differences levelled out at later stages of development in Kazakh males and in the pooled girls. The living environment was slightly but significantly associated with median age at menarche (12.89 years for urban Kazakhs to 13.43 years for rural Kazakhs). Male and female Kazakhs were older than Russians at stages 4 and 5, especially in the urban area. CONCLUSION: A relationship between pubertal status and the living environment was present in a rapidly modernizing country such as Kazakhstan.

Spirometric reference values for children and adolescents from Kazakhstan.

BACKGROUND: Spirometric parameters are influenced by several factors and many reference data are available in the literature. However, no spirometric data are available for children and adolescents from Central Asia. AIM: The study aimed to calculate spirometric reference curves on the basis of anthropometry, ethnicity (Kazakh vs. Russian) and living environment (urban vs. rural). SUBJECTS AND METHODS: Spirometry (FEV1, FVC and FEF25-75%) was performed and anthropometric measurements taken for 1926 male and 1967 female Kazakh children aged 7-18 years. RESULTS: Height explained almost all the variance of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) for both sexes, while age and inspiratory circumference contributed slightly to the prediction. Moreover, FVC and FEV1 were greater in Russians than in Kazakhs and ethnicity did enter the prediction model for these parameters. The living environment had a marginal effect on spirometry. In fact, forced expiratory flow 25-75% (FEF25-75%) was slightly higher in urban than in rural females, FVC was slightly higher in rural than in urban males, while FEV1 was not affected. Finally, among several spirometric equations available in the literature, those performing better in our children were obtained in developed countries. CONCLUSION: Anthropometry was the most important predictor of spirometry. Age and ethnicity were also predictors, while the contribution of the living environment was more limited.

Prevalence of overweight and cardiovascular risk factors in rural and urban children from Central Asia: the Kazakhstan health and nutrition examination survey.

Kazakhstan is undergoing a rapid modernization process, which carries the risk of an epidemic of obesity and cardiovascular disease. We enrolled a sample of about 50 children for every combination of gender, environment (urban vs. rural), ethnic group (Kazakh vs. Russian), and age group from 7 to 18 years, for a total of 4,808 children. Anthropometry and blood pressure were measured on all children while fasting blood cholesterol and glucose were measured only in 2,616 children aged > or =12 years. The prevalence of overweight and risk of overweight ranged from 2.8 (rural male Kazakhs) to 9.1% (urban male Russians). The prevalence of prehypertension and hypertension ranged from 8.3 (urban females) to 15.9% (rural females); that of hypercholesterolemia from 11.5 (male rural Russians) to 26.5% (female rural Kazakhs); and the overall prevalence of impaired fasting glucose was 0.1%. We conclude that overweight and cardiovascular risk factors are less prevalent in children living in Kazakhstan than in those living in Western countries. However, these figures are not negligible and suggest that preventive measures are needed to contain the epidemic of overweight and cardiovascular disease that will most likely accompany the modernization of Kazakhstan in the next years.

Italian validation of MOAS and NOSIE: a useful package for psychiatric assessment and monitoring of aggressive behaviours.

A validation of two rating scales is presented. We first translated the Modified Overt Aggression Scale (MOAS) and the Nurses' Observation Scale for In-patient Evaluation (NOSIE), which cover different aspects of psychopathology, into Italian. We then tested their validity and reliability in terms of inter-rater and internal consistency. For validity, both cases and controls were included: for the MOAS we compared patients who were aggressive (cases) to those who were presumably non-aggressive (controls). For the NOSIE, cases were acute inpatients and controls were subjects with expected stable behaviour. The Brief Psychiatric Rating Scale (BPRS) was also administered to cases in order to test convergent validity. Either the NOSIE and/or MOAS scales were administered to 358 psychiatric inpatients. A subset of these patients (131 for the MOAS and 226 for the NOSIE) was also used to test the inter-rater reliability. Both scales showed good psychometric properties. The correlation coefficients between raters were much higher than 0.75 (for the NOSIE) or 0.90 (for the MOAS), while the discriminant power between cases and controls was confirmed for both scales and good concordance with BPRS was observed. The NOSIE showed good internal consistency for all domains except neatness. In general the MOAS showed better results than the NOSIE for all psychometric properties, although both scales are suitable for monitoring the behaviour and aggression of acute ward inpatients.

Is elbow breadth a measure of frame size in non-Caucasian populations? A study in low- and high-altitude Central-Asia populations.

UNLABELLED: The concept of frame size has not undergone a thorough evaluation in non-Caucasian populations. Using data from the Central Asia High Altitude Population (CAHAP) study, we tested whether: (1) the relationship between frame size and body composition is different in high-, medium- and low-altitude populations; (2) elbow breadth is a better index of frame size than biacromial and biiliac breadth; and (3) measures of frame size are associated with blood pressure, cholesterol and triglycerides. A number of 334 male subjects aged 33 +/- 10 years (mean +/- standard deviation) were selected from the CAHAP population (n = 384) on the basis of the availability of breadth measurements. The subjects were 85 high-altitude Kirghizs, 105 medium-altitude Kazakhs, 79 low-altitude Kirghizs and 65 low-altitude Uighurs. A detailed anthropometric evaluation and blood pressure, cholesterol and trygliceride measurements were performed on all individuals. Among breadths, elbow had the lowest correlation with arm fat area, thigh fat area, calf fat area and the sum of trunk skinfolds (r < or = 0.196, P < 0.01). Even if elbow breadth did not have the highest correlation with muscularity indexes, its constantly lower association with adiposity indexes shows that it is a better measure of frame size than biacromial breadth and biiliac breadth. The relationship between frame size and body composition did not differ in high-, medium- and low-altitude subjects (P = not significant, analysis of co-variance). Only a weak association was present between breadths, blood pressure, cholesterol and triglycerides (r < or = 0.230, P < 0.01) and it was not influenced by altitude (P = not significant, analysis of co-variance). Elbow breadth was significantly correlated only with diastolic blood pressure (r = 0.121, P < 0.05). IN CONCLUSION: (1) the relationship between frame size and body composition is similar in high- and low-altitude populations; (2) elbow breadth is an index of frame size independent of altitude; and (3) elbow breadth is correlated with diastolic blood pressure, but this correlation is of doubtful biological relevance.