Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity.

PURPOSE: It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS: A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS: Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS: This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.

Prepectoral breast reconstruction with TiLoop® Bra Pocket: a single center prospective study.

OBJECTIVE: In the last decades, immediate breast reconstruction (IBR) raised in frequency, and prepectoral positioning of the implant is becoming the trend nowadays. The aim of this paper is to describe our case series in IBR with prepectoral implant placement and complete coverage of it with the TiLoop® Bra titanium-coated polypropylene mesh (TCPM), pre-shaped as a pocket. PATIENTS AND METHODS: Eighteen women with breast tumors were selected and underwent mono- or bilateral mastectomies and prepectoral IBR with tissue expanders or prostheses. After the prepectoral lodge was ready, the implants were inserted into TiLoop® Bra Pocket meshes and positioned over the pectoralis major muscle fascia. The mean surgical time of their positioning was four minutes. RESULTS: This preliminary study showed meaningful results in prepectoral IBR with TiLoop® Bra Pocket covering the implants, for we observed a reduction of implant's exposure time and risk of bacterial contamination. Of the 18 patients that underwent this procedure, only three presented complications that resolved in a maximum of four weeks. CONCLUSIONS: A considering reduction of surgical time in implant positioning was achieved, lowering exposure time and risk of complications as infection.

Oncoplastic conservative surgery for breast cancer: long-term outcomes of our first ten years experience.

OBJECTIVE: The main goal of oncoplastic breast surgery (OBS) is to optimize cosmetic outcomes and reduce patient morbidity, while still providing an oncologically-safe surgical outcome and extending the target population of conservative surgery. Although the growing number of reported experiences with oncoplastic surgery, few studies account for the long-term outcomes. PATIENTS AND METHODS: Between January 2000 and December 2010, 1024 consecutive oncoplastic surgeries were performed and prospectively included in a database. Demographic data, histological and oncological evaluation and surgical complications were recorded. The role of tumor and patients' characteristics on the development of local recurrence and metastases were assessed by multivariate analysis. RESULTS: Median follow up was 74.2 months. The average age of patients was 56.24. In 869 patients (84.9%) an invasive tumor and in 155 (15.1%) an in situ tumor (11% DCIS and 4% LIN) was found. The average size of the tumor was 24.5 mm. A positive margin presented in 67 (6.5%) patients. Forty patients (50%) underwent re-excision and 39 (49.4%) underwent mastectomy. The overall breast conservation rate was 96.2%. Reported complications were: 17 wound infections (1.7%); 106 hematomas (10.4%); 94 lymphorrheas (9.2%), 48 partial wound dehiscence (4.7%). Local recurrences (LR) were observed in 49 patients (4.7%). The risk of local recurrence was significantly higher in the group of patients with lymphovascular invasion and with high grade (G) (p < 0.05). 52 (5.07%) distant metastases were reported and the related risk was significantly higher in the group of patients with lymphovascular invasion and with negative receptors (p < 0.05). CONCLUSIONS: Oncoplastic surgery provides an acceptable oncological long-term outcome and can be used to treat with conservative surgery also a selected population of patients who would had otherwise undergone mastectomy in the past.

Active Aging and Elderly's Quality of Life: Comparing the Impact on Literature of Projects Funded by the European Union and USA.

BACKGROUND: The objective of this research is to verify whether European projects on Active Aging (AA) and Elderly Quality of Life (Qol) funded by the Seventh Framework Programme (FP7) produce an impact on literature similar to projects funded by the National Health Institute (NHI) of the United States on international literature using well-known bibliometric indicators. This effort may be useful in developing standardized and replicable procedures. METHODS: Fifteen randomly selected projects on AA and Elderly Qol concluded in August 2017 and funded by FP7 were compared to similar projects funded by the US NHI with reference to papers published (Scopus and Scholar), papers published in Q1 journals, and the number of citations of the papers linked to the projects. RESULTS: In all the indicators considered, the European projects showed no difference with the US NHI projects. CONCLUSIONS: The EU-funded AA and Qol Elderly projects have an impact on scientific literature comparable to projects funded in the United States by the NHI Agency.Our results are consistent with the data on general medical research, which indicates that, European research remains at a high level of competitiveness.In this experimental study, our methodology appeared to be convincing and reliable and it could be applied to the extent of the impact of more extensive research areas.Our research did not evaluate the relationship between funding required by research and scientific productivity.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

A Nutritional Approach to the Prevention of Cancer: from Assessment to Personalized Intervention.

Among lifestyle factors, nutrition is one of the most important determinants of health, and represents a pivotal element of cancer risk. Nonetheless, epidemiological evidences of the relationship between several cancers and specific foods and nutrients is still inadequate, and solid conclusions are missing. Indeed, caloric restriction without malnutrition is associated to cancer prevention. Food may be also the primary route of exposure to contaminants such as metals, persistent organic pollutants, and pesticides. Exposuredisease associations and the interplay with genetic susceptibility requires further studies on genetic variation, environment, lifestyle, and chronic disease in order to eliminate and reduce associated health risks, thus contributing to improve health outcomes for the population. A primary nutritional approach for Active and Healthy Ageing (AHA) has been developed by the Nutrition group of the European Innovation Partnership (EIP) on AHA. The working group on lifestyles of the Italian Ministry of Health has developed a comprehensive approach to adequate nutrition using a consensus methodology to collect and integrate the available evidences from the literature and from the Italian experiences at the regional level, to raise the interest of other experts and relevant stakeholders to outline and scale-up joint strategies for a primary nutritional approach to cancer prevention.

Sequential analysis of multistage hepatocarcinogenesis reveals that miR-100 and PLK1 dysregulation is an early event maintained along tumor progression.

MicroRNAs (miRNAs) have an important role in a wide range of physiological and pathological processes, and their dysregulation has been reported to affect the development and progression of cancers, including hepatocellular carcinoma (HCC). However, in the plethora of dysregulated miRNAs, it is largely unknown which of them have a causative role in the hepatocarcinogenic process. In the present study, we first aimed to determine changes in the expression profile of miRNAs in human HCCs and to compare them with liver tumors generated in a rat model of chemically induced HCC. We found that members of the miR-100 family (miR-100, miR-99a) were downregulated in human HCCs; a similar downregulation was also observed in rat HCCs. Their reduction was paralleled by an increased expression of polo like kinase 1 (PLK1), a target of these miRNAs. The introduction of miR-100 in HCC cells impaired their growth ability and their capability to form colonies in soft agar. Next, we aimed at investigating, in the same animal model, if dysregulation of miR-100 and PLK1 is an early or late event along the multistep process of hepatocarcinogenesis. The obtained results showed that miR-100 downregulation (i) is already evident in very early preneoplastic lesions generated 9 weeks after carcinogenic treatment; (ii) is also observed in adenomas and early HCCs; and (iii) is not simply a marker of proliferating hepatocytes. To our knowledge, this is the first work unveiling the role of a miRNA family along HCC progression.

A national survey of the prevalence of childhood overweight and obesity in Italy.

To estimate the prevalence of childhood overweight and obesity among Italian schoolchildren and to examine geographic differences and present and future implications for health care, we used data from a nationwide representative survey performed in May 2008 among third-grade students in 18 of Italy's 21 regions. Cluster sampling was used to identify classes for participation. The study population included all children aged 8-9 years whose parents agreed to opt-out consent. Parents, children and teachers completed brief questionnaires, and children were weighed and measured by trained staff using standardized equipment. Consent was obtained for 97% of 50 197 third-graders, of whom 44 676 (89%) met study inclusion criteria. Obesity levels (defined using International Obesity Task Force cut-offs) ranged from 7.5% (95% confidence intervals 6.7-8.2) in the north to 16.6% (95% confidence intervals 15.8-17.4) in the south. Behaviours known to be associated with obesity also showed geographic differences. The estimated burden of obesity-related pathologies also increased from north to south. These findings suggest the need for community as well as individual interventions in all areas of the country but with particular attention to the south.

Differences and commonalities of national field epidemiology training programmes in Europe.

From 1994 to 2009, national field epidemiology training programmes (FETP) have been installed in Spain, Germany, Italy, France and Norway. During their two year duration, different components of the FETP are devised as follows: 63-79 weeks are spent on projects in hosting institutes, 2-26 weeks in outside projects, 9-30 weeks in courses and modules, and 1-2 weeks in scientific conferences. A considerable proportion of the Spanish FETP has is provided conventional class room training . The content of the modules is very similar for all programmes. Except from the Italian programme, all focus on infectious disease epidemiology. The German and Norwegian programmes are so called EPIET-associated programmesas their participants are integrated in the modules and the supervision offered by EPIET, but salaries, facilitators, and training sites are provided by the national programme. These EPIET-associated programmes require strong communications skills in English. Alumni of all five FETP are generally working within the public health work force in their respective countries or at international level, many of them in leading functions. Although three new FETP have been installed since the last published Euroroundup in Eurosurveillance on European FETP in 2001, the progress with respect to the establishment of national FETP or EPIET-associated programmes has been slow. Member States should be aware of how much support EPIET can offer for the establishment of national FETP or EPIET-associated programmes. However, they also need to be ready to provide the necessary resources, the administrative environment and long-term dedication to make field epidemiology training work.

[Survey of the nutritional status and related risk factors in primary school children in two Italian health units]. / Stato nutrizionale dei bambini delle scuole primarie nelle ASL 4 di Terni e 5 di Bari e fattori DI rischio correlati.

During the months of May and June 2007 two prevalence studies were conducted in two local health units in Italy (Terni and Bari). The objectives of the studies were to test methods and procedures to be used in the nutritional surveillance in primary schools; to measure the prevalence of obesity and overweight in children from those schools; and to determine the prevalence of physical activity and sedentary behaviour A total of 1026 children were measured and interviewed. The refusal rate was 17% in Terni and 16% in Bari. In Terni 8% of children were obese, 24% overweight, while in Bari the corresponding values were 11% and 24%. A high prevalence of behavioural risk factors for obesity was registered such as: not eating breakfast, reduced physical activity and sedentary behaviour It was also demonstrated that parents are often unaware that their children were overweight. The results of these surveys were consistent with the high prevalence that has been registered in other studies on Italian children in the third grade. The results showed also the feasibility of surveys in schools on the nutritional situation of children in primary schools, that can be adopted as a tool for a national surveillance.

Triiodothyronine stimulates hepatocyte proliferation in two models of impaired liver regeneration.

OBJECTIVES: Liver regeneration is attenuated in old age and is substantially slower after 90% than after 70% partial hepatectomy (PH). We have previously demonstrated that the proliferative response to a primary mitogen is intact in aged mice, indicating that impaired liver regeneration is not due to loss of proliferative capacity. Here, we have investigated whether mitogenic effects of triiodothyronine (T3) could reverse the impaired regeneration of ageing or 90% hepatectomy, in the rat. MATERIALS AND METHODS: T3 (20 microg/100 g body weight) was administered to 14-month-old rats subjected to 70% PH or to young rats subjected to 90% PH. Cell-proliferative capacity was determined by bromodeoxyuridine incorporation and microscopy and changes of cell cycle-related proteins were analysed by Western blot analysis. RESULTS: Treatment of old intact rats with T3 increased cyclin D(1) expression that was followed by an enhanced proliferative response, the labelling index (LI), being 7.8% versus 1.3% of controls. T3 given before 70% PH stimulated regenerative response (LI was 10.8% versus 2.28%), and expression of cyclin D(1) and proliferating cell nuclear antigen (PCNA) 24 h after PH. Pre-treatment with T3 also improved the regenerative response of the liver after 90% hepatectomy (LI was 27.9% versus 14.2%). CONCLUSIONS: These findings show in principle that mitogen-induced hyperplasia could be applied to human therapy in patients with reduced regenerative capacity or massive loss of hepatocytes.

New findings on 3-D microanatomy of cellular structures in human tissues and organs. An HRSEM study.

We present here findings obtained on a large number of human tissues over a period of more than ten years, by our modification of the Osmium maceration method for high resolution scanning electron microscopy (HRSEM). Data are documented by original pictures which illustrate both some 3-D intracellular features not previously shown in human tissues, and results obtained in our current studies on mitochondrial morphology and on the secretory process of salivary glands. We have demonstrated that mitochondria of cells of practically all human tissues and organs have usually tubular cristae, and that even the cristae that look lamellar are joined to the inner mitochondrial membrane by tubular connexions similar to the crista junctions later seen by electron tomography. Concerning salivary glands an important result is the development of a morphometric method that allows the quantitative evaluation of the secretory events.

Effects of a generalised ban on smoking in bars and restaurants, Italy.

CONTEXT: Italy implemented a law in January 2005 banning smoking in all enclosed public spaces. OBJECTIVES: To document perceived obstacles and effects of the law and observed client smoking behaviours in bars and restaurants. DESIGN: Four surveys were conducted between December 2004 and February 2006. Protocols and questionnaires were posted on a public health website to solicit participation among local health units (LHUs). Participating LHUs randomly selected 50 bars and restaurants using the electronic Yellow Pages. Self-administered questionnaires were delivered to owners or managers of selected locales; all of them were revisited during peak hours to collect questionnaires and observe client smoking. RESULTS: Before the ban, smokers were observed in 31% of locales; 24% of owners predicted major financial losses. One year later, no smokers were observed and only 7% reported major financial losses. Only 30% had received law enforcement visits. Most owners/managers (88%) reported positive attitudes about the law and 79% reported such attitudes among clients. CONCLUSIONS: The Italian smoking law has drastically reduced smoking in bars and restaurants despite minimal enforcement visits. Perceived negative effects on profits appear limited, and the owners and managers and their clients are satisfied.

[Modes of hepatitis C virus transmission: methodological approaches]. / Les modes de transmission du virus de l'hépatite C : approches méthodologiques.

Since the mid-1990s, hepatitis C virus (HCV) transmission through blood transfusion has become very rare in western countries. Better understanding of the current modes of transmission is needed. However, risk factors have been mainly estimated on prevalent HCV infections. In this paper we describe the methods of the main case-control studies and their contribution to the knowledge on modes of HCV transmission. We also report the results of a case-control study of incident HCV infections recently carried out in France which confirms the continuing major role of IV drug use and suggests that transmission related to invasive care remained a potential source of new HCV infection between 1995 and 2001.

Surveillance of listeria infections in Europe.

In addition to the economic consequences and threats associated with outbreaks, listeriosis remains of great public health concern, as it has one of the highest case fatality rates of all the foodborne infections (20%-30%), and has common source epidemic potential. Changes in the way food is produced, distributed and stored have created the potential for diffuse and widespread outbreaks involving many countries. In 2002, a survey was carried out to assess the need for and the feasibility of a European network on listeria infections in humans. Data on surveillance systems and laboratory methods were collected through two postal surveys sent to the national Centres for communicable disease surveillance and to the listeria reference laboratories. Surveillance systems for listeria infections were in operation in 16 out of the 17 countries surveyed, and 16 countries had a national reference laboratory (NRL). All countries based their case definition of listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed at least one typing method on human strains. At least 13 countries already carried out or expressed willingness to carry out characterisation of isolates by pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from human cases following a standard protocol. The participants concluded that there was a clear added value to having a European surveillance network for listeria infections, particularly for outbreak detection and investigation, and that a surveillance network based on the existing national surveillance systems was feasible.

Induction of pancreatic acinar cell proliferation by thyroid hormone.

Thyroid hormone is known to elicit diverse cellular and metabolic effects in various organs, including mitogenesis in the rat liver. In the present study, experiments were carried out to determine whether thyroid hormone is able to stimulate cell proliferation in another quiescent organ such as the pancreas. 3,5,3'-L-tri-iodothyronine (T3) added to the diet at a concentration of 4 mg/kg caused a striking increase in nuclear bromodeoxyuridine (BrdU) incorporation of rat acinar cells 7 days after treatment (the labeling index was 46.7% in T3-treated rats vs 7.1% in controls). BrdU incorporation was limited to the acinar cells, with duct cells and islet cells being essentially negative. The increase in DNA synthesis was accompanied by the presence of several mitotic figures. Histological examination of the pancreas did not exhibit any sign of T3-induced toxicity. Determination of the apoptotic index, measurement of the serum levels of alpha-amylase and lipase, and glycemia determination did not show any increase over control values, suggesting that the enhanced proliferation of acinar cells was a direct effect induced by T3 and not a regenerative response consequent to acinar or beta-cell injury. Additional experiments showed that DNA synthesis was induced as early as 2 days after T3 treatment (the labeling index was 9.4 vs 1.9% in controls) and was associated with increased protein levels of cyclin D1, cyclin A and proliferating cell nuclear antigen, with no substantial differences in the expression of the cyclin-dependent kinase inhibitor p27. The mitogenic effect of T3 on the pancreas was not limited to the rat, since extensive acinar cell proliferation was also observed in the pancreas of mice treated with T3 for 1 week (the labeling index was 28% in T3-treated mice vs 1.8% in controls). Treatment with three other ligands of nuclear receptors, ciprofibrate, all-trans retinoic acid and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, induced little or no pancreatic cell proliferation. These results demonstrated that T3 is a powerful inducer of cell proliferation in the pancreas and suggested that pancreatic acinar cell proliferation by selected agents may have potential for therapeutic use.

Surveillance of listeria infections in Europe.

In addition to the economic consequences and threats associated with outbreaks, listeriosis remains of great public health concern, as it has one of the highest case fatality rates of all the foodborne infections (20%-30%), and has common source epidemic potential. Changes in the way food is produced, distributed and stored have created the potential for diffuse and widespread outbreaks involving many countries. In 2002, a survey was carried out to assess the need for and the feasibility of a European network on listeria infections in humans. Data on surveillance systems and laboratory methods were collected through two postal surveys sent to the national Centres for communicable disease surveillance and to the listeria reference laboratories. Surveillance systems for listeria infections were in operation in 16 out of the 17 countries surveyed, and 16 countries had a national reference laboratory (NRL). All countries based their case definition of listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed at least one typing method on human strains. At least 13 countries already carried out or expressed willingness to carry out characterisation of isolates by pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from human cases following a standard protocol. The participants concluded that there was a clear added value to having a European surveillance network for listeria infections, particularly for outbreak detection and investigation, and that a surveillance network based on the existing national surveillance systems was feasible.

Induction of hepatocyte proliferation by retinoic acid.

Retinoids have been shown to exert an anticarcinogenic effect through suppression of the cell cycle, induction of apoptosis and/or differentiation. In rat liver, in particular, retinoic acid has been shown to inhibit regeneration after partial hepatectomy, most probably through repression of the expression of c-fos and c-jun. Surprisingly enough, in spite of the proposed therapeutic effects of all-trans retinoic acid (tRA) no data are available on its effect on normal adult liver. Here, we show that tRA administration in the diet (150 mg/kg) increased DNA synthesis in mouse liver, at 1 and 2 weeks, with a return to control values at 4 weeks (labelling index was 16.5, 8.3 and 3.3%, respectively, versus control values of 1.4, 1.3 and 2.5%). Increase in mitotic index paralleled that of bromodeoxyuridine incorporation. Kinetic studies showed that entry into S phase began between 24 and 48 h, with a peak between 96 and 120 h. Histological observation of the liver and biochemical evaluation of the levels of serum glutamate-pyruvate transaminases did not reveal any evidence of cell death demonstrating that increased DNA synthesis was not due to tRA-induced liver damage and regeneration, but rather the consequence of a direct mitogenic effect. In addition, analysis of total hepatic DNA content after a 7-day treatment showed a significant increase in tRA-fed mice compared with controls (21.11 mg/100 g body wt in tRA-fed mice versus 15.67 mg/100 g body wt of controls). Hepatocyte proliferation in tRA-fed mice was associated with increased hepatic levels of cyclin D1, E and A, and enhanced expression of the member of pRb family, p107. In conclusion, the results showed that tRA induces hepatocyte proliferation in the absence of cell death, similarly to other ligands of steroid/thyroid hormone nuclear receptor superfamily. The mitogenic effect of tRA cautions about its possible use for antitumoral purposes in liver carcinogenesis.