Predictive Factors of Visual Outcome in Treatment-Naïve Diabetic Macular Edema: Preliminary Results from the Clinical Study "FOVEA".

Diabetic macular edema (DME) is a common cause of vision impairment in diabetic retinopathy. The aim of this study was to analyze the relationship between visual outcome and anatomic changes detected by traditional multimodal retinal imaging and optical coherence tomography angiography (OCTA) in DME eyes under treatment with Aflibercept. METHODS: Sixty-six DME eyes of 62 patients under treatment with intravitreal Aflibercept and with one-year follow-up were enrolled. All participants underwent a full ophthalmic evaluation, including best correct visual acuity (BCVA) measurement, spectral-domain optical coherence tomography, fluorescein angiography and OCTA, both at baseline and final examination. Fractal OCTA analysis of the superficial and deep capillary plexus (SCP and DCP) was performed to estimate vascular perfusion density and lacunarity (LAC). RESULTS: At the final examination, there was a significant improvement in terms of BCVA and central macular thickness (CMT). Furthermore, eyes with CMT <373 µm at baseline reached the higher BCVA at the last follow-up. Eyes with CMT ≥373 µm and DCP LAC <0.41 reached a higher final BCVA, if compared with eyes showing the same CMT but higher initial LAC. CONCLUSION: A 12-month treatment with intravitreal Aflibercept for DME resulted in significant visual and anatomic improvement. Multimodal retinal imaging, together with fractal OCTA analysis, may provide useful biomarkers, predictive of visual outcome in DME.

Heavy Metal(loid) Accumulation in the Ovarian Tissue of Free-Ranging Queens and Bitches Inhabiting Highly Polluted Urban Environments.

There is strong scientific evidence that exposure to environmental contaminants, such as heavy metal(loid)s (HMs), can impair female reproductive function. Pets, such as cats and dogs, who share the same habitat as humans, may be particularly useful sentinel models for detecting HMs in the ovary. In the present study, we compared the concentration of essential (Ems; Cu, Fe, Mn, Se, and Zn) and non-essential metal(loid)s (NEMs; Al, As, Cd, and Pb) in the ovarian tissues of free-ranging queens and bitches of different ages living in industrialized/highly polluted (south group) and non-polluted (north group) urban areas of the island of Sardinia, Italy. The results showed that both EMs and NEMs were present at detectable concentrations in feline and canine ovaries and their levels varied according to geographical areas and animal age. Among the EMs, Cu was found elevated in older queens and bitches inhabiting the southern area. Cadmium and lead were higher in feline and canine ovaries of older animals from the south compared to those living in the north. In addition, Cd and Pb concentrations increased in individuals of both species living in the south. These findings showed new perspectives for the use of pets as early warning sentinels of environmental pollution by HMs and for the risk of human exposure within a "One Health" approach. Pets may help to study the link between exposure to metals and female reproductive disturbances in mammals.

Contrast-enhanced ultrasound Liver Imaging Reporting and Data System: Lights and shadows in hepatocellular carcinoma and cholangiocellular carcinoma diagnosis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered a secondary examination compared to computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC), due to the risk of misdiagnosing intrahepatic cholangiocarcinoma (ICC). The introduction of CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS) might overcome this limitation. Even though data from the literature seems promising, its reliability in real-life context has not been well-established yet. AIM: To test the accuracy of CEUS LI-RADS for correctly diagnosing HCC and ICC in cirrhosis. METHODS: CEUS LI-RADS class was retrospectively assigned to 511 nodules identified in 269 patients suffering from liver cirrhosis. The diagnostic standard for all nodules was either biopsy (102 nodules) or CT/MRI (409 nodules). Common diagnostic accuracy indexes such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for the following associations: CEUS LR-5 and HCC; CEUS LR-4 and 5 merged class and HCC; CEUS LR-M and ICC; and CEUS LR-3 and malignancy. The frequency of malignant lesions in CEUS LR-3 subgroups with different CEUS patterns was also determined. Inter-rater agreement for CEUS LI-RADS class assignment and for major CEUS pattern identification was evaluated. RESULTS: CEUS LR-5 predicted HCC with a 67.6% sensitivity, 97.7% specificity, and 99.3% PPV (P < 0.001). The merging of LR-4 and 5 offered an improved 93.9% sensitivity in HCC diagnosis with a 94.3% specificity and 98.8% PPV (P < 0.001). CEUS LR-M predicted ICC with a 91.3% sensitivity, 96.7% specificity, and 99.6% NPV (P < 0.001). CEUS LR-3 predominantly included benign lesions (only 28.8% of malignancies). In this class, the hypo-hypo pattern showed a much higher rate of malignant lesions (73.3%) than the iso-iso pattern (2.6%). Inter-rater agreement between internal raters for CEUS-LR class assignment was almost perfect (n = 511, k = 0.94, P < 0.001), while the agreement among raters from separate centres was substantial (n = 50, k = 0.67, P < 0.001). Agreement was stronger for arterial phase hyperenhancement (internal k = 0.86, P < 2.7 × 10-214; external k = 0.8, P < 0.001) than washout (internal k = 0.79, P < 1.6 × 10-202; external k = 0.71, P < 0.001). CONCLUSION: CEUS LI-RADS is effective but can be improved by merging LR-4 and 5 to diagnose HCC and by splitting LR-3 into two subgroups to differentiate iso-iso nodules from other patterns.

A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events.

BACKGROUND: Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the 'next-generation' epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2. RESULTS: Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant). CONCLUSIONS: We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.

Human tissue lead (Pb) levels and amyotrophic lateral sclerosis: a systematic review and meta-analysis of case-control studies.

AIM: To combine the current scientific literature evidence and elucidate the differences of lead (Pb) bioaccumulation in human tissues by comparing amyotrophic lateral sclerosis (ALS) patients and healthy controls. METHODS: We systematically searched for case-control studies on the association of Pb levels with ALS, in human cells, tissues, and body fluids (nervous tissue, muscle, blood, cerebrospinal fluid, urine, skin appendages). Then, we performed a meta-analysis for all the tissues in which at least five case-control studies were available: whole blood (9 studies), serum/plasma (5 studies), and cerebrospinal fluid (CSF) (6 studies). Differences between cases and controls were evaluated using standardized mean difference, and combined estimates were derived using random effect maximum likelihood (REML) meta-analyses. RESULTS: Among 1734 records, we identified 46 full-text studies, of which 14 case-control studies met the meta-analysis inclusion criteria. We found higher Pb levels in ALS cases than controls in blood (standardized mean difference (SMD) = 0.61; 95% confidence interval (CI) 0.20, 1.01; p = 0.003), plasma/serum (SMD = 0.27; 95% CI - 0.16, 0.70; p = 0.26), and CSF (SMD = 0.53; 95% CI - 0.09, 1.15; p = 0.09). CONCLUSIONS: This work provides further evidence of the association between Pb bioaccumulation and ALS in body fluids. The lack of association studies in solid tissues did not allow a robust meta-analysis. Future prospective studies are needed to clarify the causality in the association of Pb bioaccumulation with ALS.

Spectral characterisation of ventricular intracardiac potentials in human post-ischaemic bipolar electrograms.

Abnormal ventricular potentials (AVPs) are frequently referred to as high-frequency deflections in intracardiac electrograms (EGMs). However, no scientific study performed a deep spectral characterisation of AVPs and physiological potentials in real bipolar intracardiac recordings across the entire frequency range imposed by their sampling frequency. In this work, the power contributions of post-ischaemic physiological potentials and AVPs, along with some spectral features, were evaluated in the frequency domain and then statistically compared to highlight specific spectral signatures for these signals. To this end, 450 bipolar EGMs from seven patients affected by post-ischaemic ventricular tachycardia were retrospectively annotated by an experienced cardiologist. Given the high variability of the morphologies observed, three different sub-classes of AVPs and two sub-categories of post-ischaemic physiological potentials were considered. All signals were acquired by the CARTO® 3 system during substrate-guided catheter ablation procedures. Our findings indicated that the main frequency contributions of physiological and pathological post-ischaemic EGMs are found below 320 Hz. Statistical analyses showed that, when biases due to the signal amplitude influence are eliminated, not only physiological potentials show greater contributions below 20 Hz whereas AVPs demonstrate higher spectral contributions above ~ 40 Hz, but several finer differences may be observed between the different AVP types.

Impact of pulsed-wave-Doppler velocity-envelope tracing techniques on classification of complete fetal cardiac cycles.

Fetal echocardiography is an operator-dependent examination technique requiring a high level of expertise. Pulsed-wave Doppler (PWD) is often used as a reference for the mechanical activity of the heart, from which several quantitative parameters can be extracted. These aspects suggest the development of software tools that can reliably identify complete and clinically meaningful fetal cardiac cycles that can enable their automatic measurement. Several scientific works have addressed the tracing of the PWD velocity envelope. In this work, we assess the different steps involved in the signal processing chains that enable PWD envelope tracing. We apply a supervised classifier trained on envelopes traced by different signal processing chains for distinguishing complete and measurable PWD heartbeats from incomplete or malformed ones, which makes it possible to determine the impact of each of the different processing steps on the detection accuracy. In this study, we collected 43 images and labeled 174,319 PWD segments from 25 pregnant women volunteers. By considering seven envelope tracing techniques and the 23 different processing steps involved in their implementation, the results of our study reveal that, compared to the steps investigated in most other works, those that achieve binarisation and envelope extraction are significantly more important (p < 0.05). The best approaches among those studied enabled greater than 98% accuracy on our large manually annotated dataset.

Cross-Sectional Study of Resilience, Positivity and Coping Strategies as Predictors of Engagement-Burnout in Undergraduate Students: Implications for Prevention and Treatment in Mental Well-Being.

In a population of young adults, this study analyzes possible linear relations of resilience and positivity to coping strategies and engagement-burnout. The aim was to establish a model with linear, associative, and predictive relations, to identify needs and make proposals for therapeutic intervention in different student profiles. A population of 1,126 undergraduate students with different student profiles gave their informed, written consent, and completed validated questionnaires (CD-RISC Scale; Positivity; Coping Strategies of Stress; Engagement, and Burnout). An ex post-facto design involved bivariate association analyses, multiple regression and structural predictions. The results offered evidence of associations and predictive relationships between resilience factors, positivity, coping strategies and engagement-burnout. The factors of resilience and positivity had significant differential associations (positive and negative) with factors of coping strategies. Their negative relationship to burnout factors, and positive relation to engagement factors, is especially important. Results of structural analysis showed an acceptable model of relationships between variables. We conclude with practical implications for therapeutic intervention: (1) the proactive factors of resilience reflect a perception of self-efficacy and the ability to change adaptively; (2) the reactive factors of resilience are usually associated with withstanding experiences of change, uncertainty or trauma.

Systematic analysis of wavelet denoising methods for neural signal processing.

Objective.Among the different approaches for denoising neural signals, wavelet-based methods are widely used due to their ability to reduce in-band noise. All wavelet denoising algorithms have a common structure, but their effectiveness strongly depends on several implementation choices, including the mother wavelet, the decomposition level, the threshold definition, and the way it is applied (i.e. the thresholding). In this work, we investigated these factors to quantitatively assess their effects on neural signals in terms of noise reduction and morphology preservation, which are important when spike sorting is required downstream.Approach.Based on the spectral characteristics of the neural signal, according to the sampling rate of the signals, we considered two possible decomposition levels and identified the best-performing mother wavelet. Then, we compared different threshold estimation and thresholding methods and, for the best ones, we also evaluated their effect on clearing the approximation coefficients. The assessments were performed on synthetic signals that had been corrupted by different types of noise and on a murine peripheral nervous system dataset, both of which were sampled at about 16 kHz. The results were statistically analysed in terms of their Pearson's correlation coefficients, root-mean-square errors, and signal-to-noise ratios.Main results.As expected, the wavelet implementation choices greatly influenced the processing performance. Overall, the Haar wavelet with a five-level decomposition, hard thresholding method, and the threshold proposed by Hanet al(2007) achieved the best outcomes. Based on the adopted performance metrics, wavelet denoising with these parametrizations outperformed conventional 300-3000 Hz linear bandpass filtering.Significance.These results can be used to guide the reasoned and accurate selection of wavelet denoising implementation choices in the context of neural signal processing, particularly when spike-morphology preservation is required.

Amyotrophic lateral sclerosis and lead: A systematic update.

Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients.

Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH+ and CD44+/CD326+ colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients' samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted.

Design and Usability Assessment of a Multi-Device SOA-Based Telecare Framework for the Elderly.

Telemonitoring is a branch of telehealth that aims at remotely monitoring vital signs, which is important for chronically ill patients and the elderly living alone. The available standalone devices and applications for the self-monitoring of health parameters largely suffer from interoperability problems; meanwhile, telemonitoring medical devices are expensive, self-contained, and are not integrated into user-friendly technological platforms for the end user. This paper presents the technical aspects and usability assessment of the telemonitoring features of the HEREiAM platform, which supports heterogeneous information technology systems. By exploiting a service-oriented architecture, the measured parameters collected by off-the-shelf Bluetooth medical devices are sent as XML documents to a private cloud that implements an interoperable health service infrastructure, which is compliant with the most recent healthcare standards and security protocols. This Android-based system is designed to be accessible both via TV and portable devices, and includes other utilities designed to support the elderly living alone. Four usability assessment sessions with quality-validated questionnaires were performed to accurately understand the ease of use, usefulness, acceptance, and quality of the proposed system. The results reveal that our system achieved very high usability scores even at its first use, and the scores did not significantly change over time during a field trial that lasted for four months, reinforcing the idea of an intuitive design. At the end of such a trial, the user-experience questionnaire achieved excellent scores in all aspects with respect to the benchmark. Good results were also reported by general practitioners who assessed the quality of their remote interfaces for telemonitoring.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Late-stage Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in Western Countries. Evidence indicates that Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a common genetic abnormality, may protect against ischemic heart and cerebrovascular disease, ocular vascular disorders, and colorectal cancer. This study was undertaken to ascertain whether G6PD deficiency may protect against AMD. Materials and Methods: 79 men with late-stage AMD and 79 male, age-matched cataract controls without AMD were recruited in March-December 2016. Smoking status, clinical history, and drug use were recorded. A blood sample was taken from each participant. Complete blood count, hemoglobin, glucose, creatinine, cholesterol, triglycerides, transaminases, bilirubin, and erythrocyte G6PD activity were measured. Stepwise logistic regression was used to investigate the association between G6PD deficiency and AMD. Results: G6PD deficiency was found in 7 (8.9%) AMD patients and 8 (10.1%) controls, a not statistically significant difference. Stepwise logistic regression disclosed that AMD was significantly associated with increased diastolic blood pressure (OR=1.09, 95% CI=1.03-1.15, P=0.02) and LDL-cholesterol (OR=1.02, 95% CI=1.0001-1.03, P=0.049) and lower values of white blood cell (WBC) count (OR=0.71, 95% CI=0.56-0.88, P=0.02) and aspartate aminotransferase (AST) (OR=0.92, 95% CI=0.85-0.99, P=0.044). Conclusion: Results suggest that G6PD deficiency has no protective effect on nor is a risk factor for AMD. Larger studies are necessary to confirm whether increased diastolic blood pressure and LDL-cholesterol and lower values of WBC count and AST are risk factors for AMD.

Antimicrobial Effect of Thymus capitatus and Citrus limon var. pompia as Raw Extracts and Nanovesicles.

In view of the increasing interest in natural antimicrobial molecules, this study screened the ability of Thymus capitatus (TC) essential oil and Citrus limon var. pompia (CLP) extract as raw extracts or incorporated in vesicular nanocarriers against Streptococcus mutans and Candida albicans. After fingerprint, TC or CLP were mixed with lecithin and water to produce liposomes, or different ratios of water/glycerol or water/propylene glycol (PG) to produce glycerosomes and penetration enhancer vesicles (PEVs), respectively. Neither the raw extracts nor the nanovesicles showed cytotoxicity against human gingival fibroblasts at all the concentrations tested (1, 10, 100 µg/mL). The disc diffusion method, MIC-MBC/MFC, time-kill assay, and transmission electron microscopy (TEM) demonstrated the highest antimicrobial potential of TC against S. mutans and C. albicans. The very high presence of the phenol, carvacrol, in TC (90.1%) could explain the lethal effect against the yeast, killing up to 70% of Candida and not just arresting its growth. CLP, rich in polyphenols, acted in a similar way to TC in reducing S. mutans, while the data showed a fungistatic rather than a fungicidal activity. The phospholipid vesicles behaved similarly, suggesting that the transported extract was not the only factor to be considered in the outcomes, but also their components had an important role. Even if other investigations are necessary, TC and CLP incorporated in nanocarriers could be a promising and safe antimicrobial in caries prevention.

Do sunscreen prevent recurrent Herpes labialis in summer?

BACKGROUND: Research results on the efficacy of sunblock sticks in avoiding or reducing Herpes labialis (HL) recurrences are contradictory and has shown mixed results, with some protection reported under experimental conditions that could not be replicated under natural conditions. OBJECTIVE: The purpose of the present work was to carry out an in vivo test on the effectiveness of a protective lip product in preventing recurrent HL in natural conditions during summer. METHODS: An exploratory randomized crossover study was performed on 20 adult volunteers who served as their own controls during the analysis. The study was conducted between May and July 2017 around the summer solstice. During the two-month period, volunteers had to perform normal daily activities and also needed to go to the beach in Sardinia; thirty subjects applying SPF 30 protection and 30 without protection. RESULTS: In individuals with stick protection, the number of HL attacks was significantly reduced. Based on association between different parameters, which emerged from the medical history and the post-test questionnaire, it was found that male individuals over 44 y of age and with Fitzpatrick skin type 2 were the most exposed to recurrence. CONCLUSION: HL recurrence rate can be reduced by using sunblock stick in summer.

Trace elements in ALS patients and their relationships with clinical severity.

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause.

Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 µmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I2  = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 µmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I2  = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn.

Prevalence of Heart Failure and Adherence to Process Indicators: Which Socio-Demographic Determinants are Involved?

Interest in chronic conditions reflects their role as the first cause of death and disability in developed countries; improving the management of these conditions is a priority for health care services. The aim of this study was to establish which sociodemographic factors influence adherence to standards of care for chronic heart failure (CHF). A generalized multilevel structural equation model was developed and applied to a sample of patients with CHF obtained from administrative data flows in six Italian regions to ascertain any associations between adherence to standards of care for CHF and sociodemographic variables. Indicators of compliance were adherence to beta-blocker therapy (BB-A) and Angiotensin Convertin Enzime inhibitor/Angiotensin Receptor Blocker therapy (ACE-A), and creatinine and electrolyte testing (CNK-T). All indicators were computed over a one-year follow-up. Among a cohort of 24,997 patients, the BB-A rate was 40.4%, the ACE-A rate 61.1%, and the CNK-T rate 57.0%. Factors found associated with adherence were gender, age, and citizenship. Our study shows an inadequate adherence to standards of care for CHF, particularly associated with certain sociodemographic characteristics. This suggests the need to improve the role of primary care in managing this chronic condition. The measures considered only apply to patients with a reduced Left Ventricular Ejection Fraction, hence a limitation of this analysis is the lack of information on left ventricular ejection.

Association of trace elements with lipid profiles and glycaemic control in patients with type 1 diabetes mellitus in northern Sardinia, Italy: An observational study.

Sardinia is an Italian region with a high incidence of type 1 diabetes mellitus. This study aimed to determine the associations of trace elements with lipid profiles and glycaemic control in patients with T1DM. A total of 192 patients with T1DM who attended the Unit of Diabetology and Metabolic Diseases in Sassari, Italy, were enrolled. Trace elements zinc, copper, selenium, chromium, and iron were measured in whole blood by sector field inductively coupled plasma mass spectrometry. The correlations between metabolic variables and the levels of trace elements were determined. Zinc was positively correlated with total cholesterol (P=0.023), low-density lipoprotein (P=0.0015), and triglycerides (P=0.027). Iron as significantly correlated with TC (P=0.0189), LDL (P=0.0121), and high-density lipoprotein (HDL) (P=0.0466). In males, Cr was positively correlated with HDL (P=0.0079) and Se, in females was correlated with TG (P=0.0113). The mean fasting plasma glucose was166.2mgdL(-1). Chromium was correlated with fasting plasma glucose (P=0.0149), particularly in males (P=0.0038). Overall, 63.5% of the patients had moderate HbA1c (7-9%). Copper was significantly correlated with HbA1c% in males (P=0.0155). In conclusion, the results of this study indicate that trace elements show different associations with lipid levels and glycaemic control in T1DM. Zinc, Fe, and Se were associated with lipid levels whereas Cu and Cr were associated with HbA1c%.

Italian deprivation index and dental caries in 12-year-old children: a multilevel Bayesian analysis.

Evidence from the literature has shown that people with a lower socioeconomic status enjoy less good health than people with a higher socioeconomic status. The Italian deprivation index (DI) was used with the aim to evaluate the association between the DMFT index and risk factors for dental caries, including city population and DI. The study included 4,305 12-year-old children living in 38 cities classified by demographic size as small, midsize and large. Zero-inflated negative binomial multilevel regression models were used to assess risk factors for DMFT and to address excess of zero DMFT and overdispersion through a Bayesian approach. The difference in the average level of DMFT among children living in cities with different DI quintile was not statistically significant (p = 0.578). The DI and ln(population), included as city-level fixed effects in the two-level variance components model, were not statistically significant. Consuming sweet drinks on average increased the mean DMFT of a susceptible child, while having a highly educated mother reduced it. Unobserved heterogeneity among cities was detected for the probability to be non-susceptible to caries (city-level variance = 0.26 with 95% credibility interval 0.09-0.57), while no territorial effect was found for the mean DMFT of the susceptible children. Our results suggest that the DI and city population did not play a role in explaining between-city variability. Interventions against social deprivation can be influential on the perception of oral health in Italian 12-year-old children to the extent that they can also affect individual level factors.