Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer

Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ～20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs in FA patients are much more frequently positive for HPV. In addition, studies have demonstrated an interaction between the HPV16 E7 oncoprotein and the FA pathway, a DNA damage response pathway deficient in FA patients. On the basis of these studies, it was hypothesized that the FA pathway contributes to repair of DNA damage induced by HPV16 E7, providing one explanation for why FA patients are predisposed to HPV-associated HNSCCs. To determine the importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2(-/-)) to establish K14E7/FancD2(-/-) and K14E7/FancD2(+/+) mice and monitored their susceptibility to HNSCC when treated with a chemical carcinogen. K14E7/FancD2(-/-) mice had a significantly higher incidence of HNSCC compared with K14E7/FancD2(+/+) mice. This difference correlated with an increased proliferative index and the increase in expression of biomarkers that are used to assess levels of DNA damage. These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7.     

Benefits of a Synbiotic Formula (Synbiotic 2000Forte<Superscript>®</Superscript>) in Critically Ill Trauma Patients: Early Results of a Randomized Controlled Trial

Background Since probiotics are considered to exert beneficial health effects by enhancing the host’s immune response, we investigated the benefits of a synbiotics treatment on the rate of infections, systemic inflammatory response syndrome (SIRS), severe sepsis, and mortality in critically ill, mechanically ventilated, multiple trauma patients. Length of stay in the intensive care unit (ICU) and number of days under mechanical ventilation were also evaluated. Method Sixty-five patients were randomized to receive once daily for 15 days a synbiotic formula (Synbiotic 2000Forte, Medipharm, Sweden) or maltodextrin as placebo. The synbiotic preparation consisted of a combination of four probiotics (10¹¹ CFU each): Pediococcus pentosaceus 5–33:3, Leuconostoc mesenteroides 32–77:1, L. paracasei ssp. paracasei 19; and L. plantarum 2,362; and inulin, oat bran, pectin, and resistant starch as prebiotics. Infections, septic complications, mortality, days under ventilatory support, and days of stay in ICU were recorded. Results Synbiotic-treated patients exhibited a significantly reduced rate of infections (P = 0.01), SIRS, severe sepsis (P = 0.02), and mortality. Days of stay in the ICU (P = 0.01) and days under mechanical ventilation were also significantly reduced in relation to placebo (P = 0.001). Conclusion The administration of this synbiotic formula in critically ill, mechanically ventilated, multiple trauma patients seems to exert beneficial effects in respect to infection and sepsis rates and to improve the patient’s response, thus reducing the duration of ventilatory support and intensive care treatment.     

Attention-deficit/hyperactivity disorder in schoolchildren in Crete

AIM: To explore the prevalence of attention-deficit/hyperactivity disorder (ADHD) in 7-y-old child residents of Crete, Greece. METHODS: The study combined information from both parents and teachers for 1708 elementary school children attending the first grade in 101 classes of 55 primary schools. A two-stage screening process was employed, including the ADHD test and a rating scale of student behaviour. Parents completed the ADHD test and teachers the rating scale of student behaviour. RESULTS: Both questionnaires were completed for 1285 (75.2%) children. Among them, 84 children (6.5%; 95% CI 5.2-7.9%) met the study criteria for ADHD. The estimated prevalence was 8.8% for boys (95% CI 6.6-11.0%) and 4.2% for girls (95% CI 2.6-5.7%). No significant differences were observed regarding urban, semi-urban or rural residence. CONCLUSION: By using a combination screening procedure, both the ADHD prevalence among first-grade schoolchildren in Crete and the gender differences in prevalence were found to be comparable to those reported from other countries. The methods used and the problems faced illustrate the challenges involved in conducting population-based studies of ADHD.     

Bcl-2/Bax ratio, mitochondrial membranes and aerobic enzyme activity in cardiomyocytes of rats after submaximal training

INTRODUCTION: Mitochondria are an active and continuous source of reactive oxygen species (ROS) during respiration. The ROS increased production during endurance training is a result of an augmented electron transport through the respiratory chains, making in this way the mitochondria a potential target for oxidative damage. The Bcl-2 protein family plays a central role in the transition of apoptotic signals towards the mitochondria in stress-induced apoptosis. AIM: The present work studied the effect of endurance training on the expression of the apoptotic proteins Bcl-2 and Bax in rat cardiomyocytes, as well as the concomitant changes in the ultrastructure of the mitochondria and activity of some enzymes residing there. MATERIAL AND METHODS: Two groups of male Wistar rats were used. One was the control and the other was trained on treadmill with submaximal loading for eight weeks. At the end of the trial, samples of the myocardium of all the experimental animals were obtained. Immunohistochemical reactions for Bcl-2 and Bax and enzymehistochemical reactions for succinate dehydrogenase and NADH2-cytochrome C-reductase were done. The results were analyzed using specialized software. Transmission electron microscopical study was carried out too. RESULTS: In the myocardium of the trained animals the expression of Bcl-2 and Bcl-2/Bax ratio were significantly higher compared to the controls. The mitochondria had intact outer and inner membranes, with no signs of swelling. Mitochondria with denser packed cristae were found predominantly. No significant differences were found in the activity of the investigated enzymes in the cardiomyocytes of the animals from both groups. CONCLUSIONS: In the myocardium of the experimental animals endurance training for eight weeks does not lead to activation of apoptotic processes via the mitochondrial pathway. This type of exercise training could be used for cardioprotection in order to elevate apoptotic threshold of cardiomyocytes.     

Information sources and level of knowledge of contraception issues among Greek women and men in the reproductive age: a country-wide survey.

OBJECTIVE: Good reproductive health depends to a great extent on how well informed people are on contraception issues. Contrary to the situation existing in many European countries, in Greece there has been a lack of studies investigating how well informed Greek women and men are. Also, the sources on which they draw are equally important. The aim of this study was to examine the knowledge of Greek women and men on issues of contraception, with the ultimate goal of identifying which groups should be the focus of prevention planning programs. METHOD: A country-wide survey was conducted through a self-administered questionnaire. The sample, numbering 1500 people, was representative of the Greek population aged 16-45 years. RESULTS: A key finding was that only a small percentage of the respondents were able to answer correctly 50% or more of the questions on knowledge of basic contraceptive issues (30.6% of women and 14.7% of men). Regarding sources of information, media and friends were reported as the primary sources of information for men of all ages and young women. The gynecologist becomes a significant source of consultation for women only after the age of 25 years. Even then, only 4% of women visiting a gynecologist do so to obtain information on prevention of pregnancy. The majority of women asking professional advice have already experienced an unwanted pregnancy. CONCLUSION: The need for health education is apparent, especially for young people.