The role of blood cholesterol quality in patients with advanced cancer receiving immune checkpoint inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) became the standard of care for several solid tumors. A limited fraction of patients (pts) achieves a long-term benefit. Plasmatic and intracellular cholesterol levels have emerged as promising biomarkers. The aim of the present study was to determine whether cholesterol efflux capacity (CEC), mediated by serum transporters (ABCA1 and ABCG1) and passive diffusion (PD), impacts on clinical outcome of advanced non-small cell lung cancer (NSCLC) and metastatic renal cell carcinoma (mRCC) pts treated with ICIs. MATERIAL AND METHODS: We retrospectively enrolled advanced NSCLC and mRCC pts consecutively treated with ICIs between October 2013 and October 2018. CEC and cholesterol loading capacity (CLC) were assessed by well-established specific cell models. As primary endpoint, CEC, PD and CLC were correlated with overall survival (OS) while the effects of these parameters on progression-free survival (PFS) and clinical benefit (CB), defined as complete/partial response or stable disease, represented secondary endpoints. RESULTS: NSCLC accounted for 94.2% of 70 enrolled cases, and serum sample suitable for CEC and PD determination was available in 68. Blood cholesterol and serum ABCA1, ABCG1, PD and CLC were associated with outcomes (OS, PFS and CB) at univariate analysis. At the multivariate analysis, only PD confirmed its positive prognostic value in terms of OS, PFS and CB. CONCLUSION: The favorable impact of cholesterol PD on clinical outcome might reflect its main conformation in mature HDL particles which potentially shape an inflamed context, ultimately promoting ICI efficacy. Further prospective studies are needed to support our findings and uncover targetable pathways.

POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.

POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype-phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA-binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3-related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype-phenotype correlations.

Intestinal differentiation involves cleavage of histone H3 N-terminal tails by multiple proteases.

The proteolytic cleavage of histone tails, also termed histone clipping, has been described as a mechanism for permanent removal of post-translational modifications (PTMs) from histone proteins. Such activity has been ascribed to ensure regulatory function in key cellular processes such as differentiation, senescence and transcriptional control, for which different histone-specific proteases have been described. However, all these studies were exclusively performed using cell lines cultured in vitro and no clear evidence that histone clipping is regulated in vivo has been reported. Here we show that histone H3 N-terminal tails undergo extensive cleavage in the differentiated cells of the villi in mouse intestinal epithelium. Combining biochemical methods, 3D organoid cultures and in vivo approaches, we demonstrate that intestinal H3 clipping is the result of multiple proteolytic activities. We identified Trypsins and Cathepsin L as specific H3 tail proteases active in small intestinal differentiated cells and showed that their proteolytic activity is differentially affected by the PTM pattern of histone H3 tails. Together, our findings provide in vivo evidence of H3 tail proteolysis in mammalian tissues, directly linking H3 clipping to cell differentiation.

Identification of Proteins Involved in Cell Membrane Permeabilization by Nanosecond Electric Pulses (nsEP).

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in YP uptake. The respective proteins could be part of electropermeabilization lesions or increase their lifespan. In contrast, as many as 39 genes were identified as likely hits for the increased YP uptake, meaning that the respective proteins contributed to membrane stability or repair after nsEP. The expression level of eight genes in different types of human cells showed strong correlation (R > 0.9, p < 0.02) with their LD50 for lethal nsEP treatments, and could potentially be used as a criterion for the selectivity and efficiency of hyperplasia ablations with nsEP.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects.

OBJECTIVE: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. METHODS: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. RESULTS: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. CONCLUSION: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

The role of lipid metabolism in shaping the expansion and the function of regulatory T cells.

Metabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs.

Headache in progressive facial hemiatrophy (Parry-Romberg syndrome): A paradigmatic case and systematic review of the literature.

BACKGROUND: Parry-Romberg syndrome is a neuro-cutaneous disease characterized by progressive hemifacial atrophy. Although common, headache in this population is scarcely reported in the literature. OBJECTIVE: To evaluate the clinical features of headache in pediatric and adult patients with Parry-Romberg syndrome, and to discuss diagnostic and treatment approaches of headache in Parry-Romberg syndrome. METHODS: We conducted a systematic review in accordance with PRISMA guidelines. We searched the MEDLINE database to identify eligible studies and identified patients with Parry-Romberg syndrome and headache. We further reported a paradigmatic case with a complex headache disorder and described its management and outcome. RESULTS: We identified 74 articles, 41 of which were included in the analysis. A total of 52 patients (55.8% female) were included for data analysis. The main age at onset of headache was 20 years (SD 15.2; range 3-56). A diagnosis of migraine was made in 53.9%. Abnormal brain imaging was found in 82.2% of patients. CONCLUSION: Long-term follow-up of patients is required, because headache may develop (and evolve) at any time over the course of the disease. Primary and secondary headaches often co-occur in patients with Parry-Romberg syndrome. Further research into the underlying etiopathogenesis and therapeutic targets would be recommended.

Case Report of a Massive Life-threatening Neonatal Thrombosis Treated With a Targeted, Goal-oriented Scheme of Urokinase.

BACKGROUND: Thrombotic events are severe, often under-diagnosed, complications occurring in newborn infants during their hospital stay. Currently, there is no consensus regarding the optimal treatment scheme for thrombolysis in neonates. OBSERVATIONS: We present the case of a newborn suffering from a life-threatening thrombosis. Diagnosis was suggested by a gradual increase of C-reactive protein, with repeatedly normal procalcitonin. Thrombosis was successfully and safely treated with a long scheme of 21 days of urokinase, supported by vascular ultrasound and d-dimer trend. CONCLUSIONS: Laboratory and ultrasound results may help in adjusting the duration of the thrombolytic treatment, allowing for longer therapeutic schemes that could optimize treatment success. In addition, our case may suggest a possible combined role of C-reactive protein and procalcitonin as an early diagnostic aid in neonatal thrombosis.

Self-perceived workplace discrimination and mental health among immigrant workers in Italy: a cross-sectional study.

BACKGROUND: The process of immigration is associated with poor mental and physical health. While the workplace represents an important context of social integration, previous studies evaluating the effect of discrimination experienced in the workplace found worse mental health status among immigrants. The aim of this study was to investigate whether self-perceived workplace discrimination has any role in the mental health status of immigrants living and working in Italy, evaluating the contribution of other personal experiences, such as loneliness and life satisfaction. METHODS: A cross-sectional study was conducted on a sample of 12,408 immigrants (aged 15-64) living and working in Italy. Data were derived from the first national survey on immigrants carried out by the Italian National Institute of Statistics (Istat). Mental health status was measured through the Mental Component Summary (MCS) of the SF-12 questionnaire. A linear multivariate linear regression was carried out to evaluate the association between mental health status, self-perceived workplace discrimination, and sociodemographic factors; path analysis was used to quantify the mediation effect of self-perceived loneliness, level of life satisfaction, and the Physical Component Summary (PCS). RESULTS: Mental health status was inversely associated (p < 0.001) with self-perceived workplace discrimination (ß:-1.737), self-perceived loneliness (ß:-2.653), and physical health status (ß:-0.089); it was directly associated with level of life satisfaction (ß:1.122). As confirmed by the path analysis, the effect of self-perceived workplace discrimination on MCS was mediated by the other factors considered: self-perceived loneliness (11.9%), level of life satisfaction (20.7%), and physical health status (3.9%). CONCLUSIONS: Our study suggests that self-perceived workplace discrimination is associated with worse mental health status in immigrant workers through personal experiences in the workplace and explains the effect of the exposure to workplace discrimination on immigrants' psychological well-being. Our findings suggest that an overall public health response is needed to facilitate the social integration of immigrants and their access to health services, particularly those services that address mental health issues.

RNA Flow Cytometry for the Study of T Cell Metabolism.

T cells undergo activation and differentiation programs along a continuum of states that can be tracked through flow cytometry using a combination of surface and intracellular markers. Such dynamic behavior is the result of transcriptional and post-transcriptional events, initiated and sustained by the activation of specific transcription factors and by epigenetic remodeling. These signaling pathways are tightly integrated with metabolic routes in a bidirectional manner: on the one hand, T cell receptors and costimulatory molecules activate metabolic reprogramming; on the other hand, metabolites modify T cell transcriptional programs and functions. Flow cytometry represents an invaluable tool to analyze the integration of phenotypical, functional, metabolic and transcriptional features, at the single cell level in heterogeneous T cell populations, and from complex microenvironments, with potential clinical application in monitoring the efficacy of cancer immunotherapy. Here, we review the most recent advances in flow cytometry-based analysis of gene expression, in combination with indicators of mitochondrial activity, with the aim of revealing and characterizing major metabolic pathways in T cells.

Noninvasive Evaluation of Liver Fibrosis in a Sample of Putative Inactive HBV Carriers in Rome, Italy.

BACKGROUND: Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. OBJECTIVES: The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. METHODS: Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. RESULTS: Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001). CONCLUSIONS: Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify "false" inactive carriers.

PRC2 preserves intestinal progenitors and restricts secretory lineage commitment.

Chromatin modifications shape cell heterogeneity by activating and repressing defined sets of genes involved in cell proliferation, differentiation and development. Polycomb-repressive complexes (PRCs) act synergistically during development and differentiation by maintaining transcriptional repression of common genes. PRC2 exerts this activity by catalysing H3K27 trimethylation. Here, we show that in the intestinal epithelium PRC2 is required to sustain progenitor cell proliferation and the correct balance between secretory and absorptive lineage differentiation programs. Using genetic models, we show that PRC2 activity is largely dispensable for intestinal stem cell maintenance but is strictly required for radiation-induced regeneration by preventing Cdkn2a transcription. Combining these models with genomewide molecular analysis, we further demonstrate that preferential accumulation of secretory cells does not result from impaired proliferation of progenitor cells induced by Cdkn2a activation but rather from direct regulation of transcription factors responsible for secretory lineage commitment. Overall, our data uncover a dual role of PRC2 in intestinal homeostasis highlighting the importance of this repressive layer in controlling cell plasticity and lineage choices in adult tissues.

[Evaluating health care of the immigrant population in Italy through indicators of a national monitoring system]. / Valutazione dell'assistenza sanitaria della popolazione immigrata in Italia attraverso alcuni indicatori di un sistema nazionale di monitoraggio.

OBJECTIVES: to evaluate maternal and child healthcare, avoidable hospitalisation, access to emergency services among immigrants in Italy. DESIGN: cross sectional study of some health and health care indicators among Italian and foreign population residing in Italy in 2016-2017. SETTING AND PARTICIPANTS: indicators based on the national monitoring system coordinated by the Italian National Institute for Health, Migration and Poverty (INMP) of Rome, calculated on perinatal care (CedAP), hospital discharge (SDO), emergency services (EMUR) archives for the years 2016-2017, by of the following regions: Piedmont, Trento, Bolzano, Emilia-Romagna, Tuscany, Umbria, Lazio, Basilicata, Sicily. MAIN OUTCOME MEASURES: number and timeliness of pregnancy visits, number of ultrasounds, invasive prenatal investigations; perinatal mortality rates, birth weight, Apgar score at 5 minutes, need for neonatal resuscitation; standardized rates of avoidable hospitalisation and access to emergency services by triage code. RESULTS: more often than Italians, immigrant women have during pregnancy: less than 5 gynaecological examination (16.3% vs 8.5%), first examination after the 12th week of gestational age (12.5% vs 3.8%), less than 2 ultrasounds (3.8% vs 1.0%). Higher perinatal mortality rates among immigrants compared to Italians (3.6 vs 2.3 x1,000). Higher standardized rates (x1,000) among immigrants compared to Italians of avoidable hospitalisation (men: 2.1 vs 1.4; women: 0.9 vs 0.7) and of white triage codes in emergency (men: 62.0 vs 32.7; women: 52.9 vs 31.4). CONCLUSIONS: study findings show differences in access and outcomes of healthcare between Italians and immigrants. National monitoring system of indicators, coordinated by INMP, represents a useful tool for healthcare intervention policies aimed to health equity.

The geography and economics of forgoing medical examinations or therapeutic treatments in Italy during the economic crisis.

BACKGROUND: In Italy, the number of individuals who have forgone medical examinations or treatments for economic reasons is one of the highest in Europe. During the global economic crisis of 2008, the restrictive policies concerning access to healthcare and the quality of these services, which differs widely throughout the country, may have accentuated the territorial differences in unmet needs, thereby penalizing the more disadvantaged segments of the population. The study aimed at evaluating the geographical and socioeconomic differences, in particular the risk of poverty, that influence forgoing healthcare services in Italy. METHODS: Cross-sectional Italian data from the 2004-2015 European Survey on Income and Living Conditions (EU-SILC) were used. Hierarchical logistic models were tested, using as the outcome unmet needs for medical examinations or treatment in the preceding 12 months, and as risk factor the condition of being at risk of poverty. Age, sex, citizenship, educational level, presence of chronic or severely limiting diseases and self-perceived health were used as adjustment factors. Analyses were stratified over three time periods: pre-crisis (2004-2007), initial phase of the crisis (2008-2012) and second phase of the crisis (2013-2015). RESULTS: In Central Italy and particularly in Southern Italy, a marked increase (9.9% in 2013-2015) was seen in the overall rate of unmet needs as well as in that of unmet needs due to economic reasons. The probability of unmet needs was higher, and increased over time, for those at risk of poverty (aOR = 1.54 in 2004-07, aOR = 1.70 in 2008-12, aOR = 2.21 in 2013-15). Individuals with a low educational level, who had a chronic or severely limiting disease, who perceived their health as not good and immigrants had a higher risk of forgoing healthcare. The regions in Southern Italy had a significantly higher probability of unmet needs. CONCLUSIONS: A strong association was found between the probability of forgoing medical examination or treatment and being at risk of poverty. Study results underline the need for healthcare policies aimed at facilitating access to healthcare services, particularly in the South, by developing a progressive mechanism of contribution to healthcare costs proportional to income and by guaranteeing free access to the poor.

Dry powder inhaler of colistimethate sodium for lung infections in cystic fibrosis: optimization of powder construction.

Colistimethate sodium (CMS) for treatment of lung infections in cystic fibrosis patient was transformed into a dry powder for inhalation by spray drying. Design of Experiment was applied for understanding the role of the spray-drying process parameters on the critical quality attributes of the CMS spray-dried (SD) powders and agglomerates thereof. Eleven experimental SD microparticle powders were constructed under different process conditions according to a central composite design. The SD microparticles were then agglomerated in soft pellets. Eleven physico-chemical characteristics of SD CMS microparticle powders or agglomerates thereof were selected as critical quality attributes. The yield of SD process was higher than 75%. The emitted fraction of agglomerates from RS01 inhaler was 75-84%, and the fine particle fraction (particles <5 µm) was between 58% and 62%. The quality attributes of CMS SD powders and respective agglomerates that were significantly influenced by spray-drying process parameters were residual solvent and drug content of the SD microparticles as well as bulk density and respirable dose of the agglomerates. These attributes were also affected by the combination of the process variables. The air aspiration rate was found as the most positively influential on drug and solvent content and respirable dose. The residual solvent content significantly influenced the powder bulk properties and aerodynamic behavior of the agglomerates, i.e. quality attributes that govern drug metering in the device and the particles lungs deposition. Agglomerates of CMS SD microparticles, in combination with RS01 DPI, showed satisfactory results in terms of dose emitted and fine particle fraction.

Comparative Optimism: Relative Risk Perception and Behavioral Response to Lead Exposure.

Despite their true exposure, individuals with Comparative Optimism consider themselves less prone to the adverse health effects of pollution. Since individuals' response to a given environmental risk is affected by their appraisal of the risk, those with Comparative Optimism may be less likely to engage in prescribed behaviors or to do so at the urgency required of the given risk. Such limited or delayed response can amplify the risk instead of reducing it. Thus, there is a need to understand if Comparative Optimism applies to pollutants with irreversible adverse health effects as it would impose a higher burden. There is also a need to know which segments of the population are prone to Comparative Optimism and how it manifests in terms of activities that can enhance exposure. Doing so will allow public health professionals address gaps in risk communication and management efforts and help improve environmental health outcomes. Using survey data, we assess the presence, behavioral and socioeconomic predictors, and implications of Comparative Optimism for communicating and managing lead exposure risk in an urban setting. Our results indicate that a large share of the population has Comparative Optimism for lead exposure, despite living in a city that has a relatively higher lead poisoning burden. We also found that ethnicity, income, length of stay at residence, among others, predict Comparative Optimism, suggesting that Comparative Optimism may predict elevated blood lead level.

[The inappropriateness in the use of female cancer screening tests in Italy: over- and under-utilization determinants]. / L'inappropriatezza nell'uso dei test di screening oncologici femminili in Italia: determinanti di sovra e sottoutilizzo.

OBJECTIVES: to identify the determinants of over and under-use of Pap test and mammography in the screening programme target population. DESIGN: cross-sectional study. SETTING E PARTICIPANTS: we used data from the National Health interview conducted by the Italian National Institute of Statistics in 2012-2013 obtaining nation-wide representative samples of the female resident population aged 25-64 years (No. 32,831; target age of Pap test) and 50-69 years (No. 16,459; target age of mammography). MAIN OUTCOME MEASURES: overall coverage: proportion of women in the target age with at least one test in lifetime; appropriate coverage: proportion of women reporting to have at least one or more tests following the first one with the recommended frequency (three and two years for Pap test and mammography, respectively); over-use: women reporting to repeat test at higher frequency; under-use: women reporting not having ever had a test or having test at longer intervals. For frequency outcomes, only women aged 28-64 years and 52-69 years were included for Pap test and mammography, respectively. RESULTS: 11.9% of women have Pap test at the recommended frequency, 48.5% at shorter intervals, and 19.6% at longer intervals than recommended, while 20.0% never had a Pap test at all (39.6% under-use). 41.1% of women have a mammography at the recommended interval, 18.4% at shorter intervals, and 20.2% at longer intervals, while 20.3% never had a mammography at all. For both tests, in the North-East higher appropriate coverage and less over-use are observed, while in the South more under-use is highlighted. Young, foreigners, single, less educated, and unoccupied women have, at the same time, more over- and under-use for Pap test. Foreigner women reporting economic difficulties and single women have more mammography over and under-use. CONCLUSIONS: Pap test and, in a minor measure, mammography over-use are relevant in Italy, while large part of the population is still not covered.

Infectious and dermatological diseases among arriving migrants on the Italian coasts.

Background: Since 2008 Italy has been the destination of the 'central Mediterranean route', used by migrants to reach Europe. The aim of this study is to describe demographic characteristics and health problems of migrants at the time of arrival on the Italian coasts, focussing on dermatological and infectious diseases. Methods: Cross-sectional study of data routinely collected (n = 6, 188) by the National Institute for Health Migration and Poverty (INMP) in the centres for migrants of Lampedusa and Trapani-Milo (2015-16). Logistic models were performed to identify factors associated with scabies, varicella and the occurrence of two or more not related diagnosis. Results: The average age was 21.6 years; 83.5% of the patients were males. The most frequent countries of origin were Eritrea, Nigeria, and Somalia. The most frequent diagnosis was scabies (58% of patients), skin infections, pediculosis and dermatitis; respiratory infections and varicella were the most represented infectious diseases. The diagnosis of scabies was more probable among Somalis (OR: 11.60) and Eritreans (OR: 10.05); the diagnosis of varicella was more probable among Ghanaians (OR: 13.58) and Nigerians (OR: 9.79). Somalis (OR: 4.10) and Eritreans (OR: 3.32) were the patients more likely to receive two or more diagnosis. Conclusions: The majority of the diseases affecting migrants is in most cases, related to the migration experience and is likely not to represent a major threat for public health. Up-to-date information regarding the burden of diseases is needed in order to identify the health needs of incoming migrants and to arrange the appropriate response in terms of health services provision.

Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study.

Decreased antioxidant capacity and increased oxidative stress have been observed in fibromyalgia patients. Some trials have also shown that CoQ10 levels are reduced in these patients but that supplementation can restore levels and reduce fibromyalgia symptoms, including pain and fatigue. We evaluated the effect of administration of a finished form of CoQ10 (DDM Chinone®) at a dose of 200 mg×2/day in 22 female subjects with a diagnosis of fibromyalgia in a randomized, open-label, cross-over study. Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue (by ~22%) and sleep disturbance (by ~33%). These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia.

The variation in the health status of immigrants and Italians during the global crisis and the role of socioeconomic factors.

BACKGROUND: The effects of the recent global economic and financial crisis especially affected the most vulnerable social groups. Objective of the study was to investigate variation of self-perceived health status in Italians and immigrants during the economic global crisis, focusing on demographic and socioeconomic factors. METHODS: Through a cross-sectional design we analyzed the national sample of multipurpose surveys "Health conditions and use of health services" (2005 and 2013) conducted by the Italian National Institute of Statistics (ISTAT). Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, derived from SF-12 questionnaire, were assumed as study outcome, dichotomizing variables distribution at 1st quartile. Prevalence rate ratios (PRR) were estimated through log-binomial regression models, stratified by citizenship and gender, evaluating the association between PCS and MCS with surveys' year, adjusting for age, educational level, employment status, self-perceived economic resources, smoking habits, body mass index. RESULTS: From 2005 to 2013 the proportion of people not employed or reporting scarce/insufficient economic resources increased, especially among men, in particular immigrants. Compared with 2005 we observed in 2013 among Italians a significant lower probability of worse PCS (PRR = 0.96 both for males and females), while no differences were observed among immigrants; a higher probability of worse MCS was observed, particularly among men (Italians: PRR = 1.26;95%CI:1.22-1.29; immigrants: PRR = 1.19;95%CI:1.03-1.38). Self-perceived scarce/insufficient economic resources were strongly and significantly associated with worse PCS and MCS for all subgroups. Lower educational level was strongly associated with worse PCS in Italians and slightly associated with worse MCS for all subgroups. Being not employed was associated with worse health status, especially mental health among men. CONCLUSIONS: Our findings support the hypothesis that economic global crisis could have negatively affected health status, particularly mental health, of Italians and immigrants. Furthermore, results suggest socioeconomic inequalities increase, in economic resources availability dimension. In a context of public health resources' limitation due to financial crisis, policy decision makers and health service managers must face the challenge of equity in health.