Environmental factors affecting female fertility.

INTRODUCTION: Over the recent years, scientific community has increased its interest on solving problems of female fertility pathology. Many factors acting separately or in combination affect significantly the reproductive life of a woman. This review summarizes current evidence regarding the direct and/or indirect action of environmental factors and endocrine disrupting chemicals (EDCs; i.e. heavy metals, plasticizers, parabens, industrial chemicals, pesticides, or medications, by-products, anti-bacterial agents, perfluorochemicals) upon assisted and non-assisted female fertility, extracted from in vivo and in vitro animal and human published data. Transgenerational effects which could have been caused epigenetically by the action of EDCs have been raised. METHODS: This narrative review englobes and describes data from in vitro and in vivo animal and human studies with regard to the action of environmental factors, which include EDCs, on female fertility following the questions for narrative reviews of the SANRA (a scale for the quality assessment of narrative review articles). The identification of the studies was done: through the PubMed Central and the PubMed of the MEDLINE, the Google Scholar database and the Cochrane Library database until December 2023 combining appropriate keywords ("specific environmental factors" including "EDCs" AND "specific negative fertility outcomes"); by manual scanning of references from selected articles and reviews focusing on these subjects. It includes references to EDCs-induced transgenerational effects. RESULTS: From the reported evidence emerge negative or positive associations between specific environmental factors or EDCs and infertility outcomes such as infertility indices, disrupted maturation of the oocytes, anovulation, deranged transportation of the embryo and failure of implantation. CONCLUSION: The revealed adverse outcomes related to female fertility could be attributed to exposure to specific environmental factors such as temperature, climate, radiation, air pollutants, nutrition, toxic substances and EDCs. The recognition of fertility hazards related to the environment will permit the limitation of exposure to them, will improve female fertility and protect the health potential of future generations.

Diagnostic and therapeutic use of oral micronized progesterone in endocrinology.

Progesterone is a natural steroid hormone, while progestins are synthetic molecules. In the female reproductive system, progesterone contributes to the control of luteinizing hormone and follicle-stimulating hormone secretion and their pulsatility, via its receptors on the kisspeptin, neurokinin B, and dynorphin neurons in the hypothalamus. Progesterone together with estradiol controls the cyclic changes of proliferation and decidualization of the endometrium; exerts anti-mitogenic actions on endometrial epithelial cells; regulates normal menstrual bleeding; contributes to fertilization and pregnancy maintenance; participates in the onset of labor. In addition, it exerts numerous effects on other endocrine systems. Micronized progesterone (MP) is natural progesterone with increased bioavailability, due to its pharmacotechnical micronized structure, which makes it an attractive diagnostic and therapeutic tool. This critical literature review aims to summarize and put forward the potential diagnostic and therapeutic uses of MP in the field of endocrinology. During reproductive life, MP is used for diagnostic purposes in the evaluation of primary or secondary amenorrhea as a challenge test. Moreover, it can be prescribed to women presenting with amenorrhea or oligomenorrhea for induction of withdrawal bleeding, in order to time blood-sampling for diagnostic purposes in early follicular phase. Therapeutically, MP, alone or combined with estrogens, is a useful tool in various endocrine disorders including primary amenorrhea, abnormal uterine bleeding due to disordered ovulation, luteal phase deficiency, premenstrual syndrome, polycystic ovary syndrome, secondary amenorrhea [functional hypothalamic amenorrhea, premature ovarian insufficiency], perimenopause and menopause. When administrated per os, acting as a neurosteroid directly or through its metabolites, it exerts beneficial effects on brain function such as alleviation of symptoms of anxiety and depression, asw well as of sleep problems, while it improves working memory in peri- and menopausal women. Micronized progesterone preserves full potential of progesterone activity, without presenting many of the side-effects of progestins. Although it has been associated with more frequent drowsiness and dizziness, it can be well tolerated with nocturnal administration. Because of its better safety profile, especially with regard to metabolic ailments, breast cancer risk and veno-thromboembolism risk, MP is the preferred option for individuals with an increased risk of cardiovascular and metabolic diseases and of all-cause mortality.

Secondary Prevention of Diabetes Type 1 with Oral Calcitriol and Analogs, the PRECAL Study.

Screening for Type 1 Diabetes (T1D, incidence 1:300) with T1D autoantibodies (T1Ab) at ages 2 and 6, while sensitive, lacks a preventive strategy. Cholecalciferol 2000 IU daily since birth reduced T1D by 80% at 1 year. T1D-associated T1Ab negativized within 0.6 years with oral calcitriol in 12 children. To further investigate secondary prevention of T1D with calcitriol and its less calcemic analog, paricalcitol, we initiated a prospective interventional non-randomized clinical trial, the PRECAL study (ISRCTN17354692). In total, 50 high-risk children were included: 44 were positive for T1Ab, and 6 had predisposing for T1D HLA genotypes. Nine T1Ab+ patients had variable impaired glucose tolerance (IGT), four had pre-T1D (3 T1Ab+, 1 HLA+), nine had T1Ab+ new-onset T1D not requiring insulin at diagnosis. T1Ab, thyroid/anti-transglutaminase Abs, glucose/calcium metabolism were determined prior and q3-6 months on calcitriol, 0.05 mcg/Kg/day, or paricalcitol 1-4 mcg × 1-3 times/day p.o. while on cholecalciferol repletion. Available data on 42 (7 dropouts, 1 follow-up < 3 months) patients included: all 26 without pre-T1D/T1D followed for 3.06 (0.5-10) years negativized T1Ab (15 +IAA, 3 IA2, 4 ICA, 2 +GAD, 1 +IAA/+GAD, 1 +ICA/+GAD) within 0.57 (0.32-1.3) years or did not develop to T1D (5 +HLA, follow-up 3 (1-4) years). From four pre-T1D cases, one negativized T1Ab (follow-up 1 year), one +HLA did not progress to T1D (follow-up 3.3 years) and two +T1Ab patients developed T1D in 6 months/3 years. Three out of nine T1D cases progressed immediately to overt disease, six underwent complete remission for 1 year (1 month-2 years). Five +T1Ab patients relapsed and negativized again after resuming therapy. Four (aged <3 years) negativized anti-TPO/TG, and two anti-transglutaminase-IgA. Eight presented mild hypercalciuria/hypercalcemia, resolving with dose titration/discontinuation. Secondary prevention of T1D with calcitriol and paricalcitol seems possible and reasonably safe, if started soon enough after seroconversion.

Effects of a Diabetes Sports Summer Camp on the Levels of Physical Activity and Dimensions of Health-Related Quality of Life in Young Patients with Diabetes Mellitus Type 1: A Randomized Controlled Trial.

Physical activity (PA) is considered an important part of the treatment of children with diabetes mellitus type 1 (T1DM). Furthermore, health-related quality of life (HRQoL) affects both the physical and mental health of patients with T1DM. The purpose of the study was to evaluate through a randomized controlled trial the impact of participation in a summer diabetes sports camp on the PA and HRQoL of children and adolescents with T1DM. Eighty-four children and adolescents with T1DM were randomly assigned into an intervention (M = 12.64, SD = 1.82, 30 female) and a control group (M = 12.67, SD = 2.50, 30 female). Intervention group participants attended a ten-day summer diabetes sports camp which included an intensive program of PA (6 h of daily PA), educational and entertaining activities as well as education on the importance of PA in the management of the disease. At baseline and at the end of the study, participants completed measures of physical activity, self-esteem, depression, health status, intention to change behavior, and life satisfaction. Results of the two-way repeated measures analysis showed no statistically significant group differences in PA levels (p < 0.05) and HRQoL parameters (p < 0.05 for all parameters). In conclusion, the results did not support the effectiveness of a 10-day diabetes sports camp on PA levels and HRQoL for children with T1DM. Longer interventions may be more effective in exerting positive influence on trait parameters of children with T1DM's quality of life. Participation in such programs on multiple occasions should be evaluated in the future.

Environmental factors affecting pregnancy outcomes.

INTRODUCTION: Pregnancy represents a fragile period in the life of a woman, vulnerable to hazardous environmental substances which might affect maternal and fetal metabolism. The possible influence of environmental factors, including endocrine disrupting chemicals (EDCs), upon the mother and the fetus before and/or during pregnancy might be associated directly and/or indirectly to deleterious pregnancy outcomes. Because the existence of such associations would be, to our view, of major importance to the scientific community, their investigation is the scope of this critical review. METHODS: This critical review includes in vivo animal and human studies regarding the role of environmental factors, including EDCs, on pregnancy outcomes complying with the SANRA (a scale for the quality assessment of narrative review articles) questions for narrative reviews. Studies were identified by searching the MEDLINE (PubMed and PubMed Central), the Cochrane library and the Google Scholar databases till October 2022 with the combinations of the appropriate key words (detailed environmental factors including EDCs AND detailed negative pregnancy outcomes) as well as by scanning references from already included articles and relevant reviews manually. Because environmental factors and EDCs have been associated to epigenetic alterations, special care has been given to EDC-induced transgenerational effects on pregnancy outcomes. RESULTS: The existing evidence suggests positive associations between specific environmental factors and negative pregnancy outcomes such as ectopic pregnancies, pregnancy losses, gestational diabetes, hypertensive disorders of pregnancy, preterm births, birth defects, intrauterine growth restriction, and small or large for gestational age babies. CONCLUSION: Environmental factors and EDCs may have a catalytic effect on the course and the outcomes of pregnancy.

Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea.

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols.

The Effect of Physical Exercise on Oxidation Capacity and Utero-Placental Circulation in Pregnancies with Gestational Diabetes Mellitus and Uncomplicated Pregnancies, a Pilot Study.

Background: Gestational diabetes mellitus (GDM) is associated with aggravated oxidation capacity and utero-placental circulation, while aerobic exercise could improve both. The study aims to assess oxidation capacity and utero-placental circulation before and after a bout of aerobic exercise in GDM and uncomplicated pregnancies.; Methods: In this cross-sectional study, women with GDM (GDMs) and women with uncomplicated pregnancies(controls), underwent 30 min of moderate intensity cycling. Total antioxidant capacity (TAC), catalase activity (CAT), reduced glutathione (GSH), Uterine Arteries (UtA PI) and Umbilical Artery (UmA PI) pulsatility indexes were estimated prior-to, immediately after and one hour after exercise; Results: In each group, 25 pregnant women were included. In both groups, between prior-to and immediately after exercise, TAC and CAT increased, while GSH decreased, (p < 0.001). In GDMs, CAT was lower than controls at any time point (p < 0.05), while in GDMs delta(Δ) CAT (prior-to and immediately after exercise) was lower than controls (p = 0.003). In GDMs, UtA PI centiles decreased between prior-to and either immediately or one hour after exercise, while they did not change in controls. In GDMs, pre-conceptional BMI and weight gain predicted negatively ΔTAC (prior-to to one hour after exercise); Conclusions: Moderate intensity exercise bout improves oxidation capacity in GDM and uncomplicated pregnancies, although at a lesser extent in the former. Exercise leads to decreased UtA arteries resistance in women with GDM.

Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy.

Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms' tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.

Effects on Puberty of Nutrition-Mediated Endocrine Disruptors Employed in Agriculture.

Pesticide residues are largely found in daily consumed food because of their extensive use in farming and their long half-life, which prolongs their presence in the environment. Many of these pesticides act as endocrine-disrupting chemicals after pre- or postnatal exposure, significantly affecting, among other things, the time of puberty onset, progression, and completion. In humans, precocious or delayed puberty, and early or delayed sexual maturation, may entail several negative long-term health implications. In this review, we summarize the current evidence on the impact of endocrine-disrupting pesticides upon the timing of the landmarks of female and male puberty in both animals (vaginal opening, first estrus, and balanopreputial separation) and humans (thelarche, menarche, gonadarche). Moreover, we explore the possible mechanisms of action of the reviewed endocrine-disrupting pesticides on the human reproductive system. Access to safe, healthy, and nutritious food is fundamental for the maintenance of health and wellbeing. Eliminating the presence of hazardous chemicals in largely consumed food products may increase their nutritional value and be proven beneficial for overall health. Consequently, understanding the effects of human exposure to hazardous endocrine-disrupting pesticides, and legislating against their circulation, are of major importance for the protection of health in vulnerable populations, such as children and adolescents.

The Effect of Dietary Supplements on Oxidative Stress in Pregnant Women with Gestational Diabetes Mellitus: A Network Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) exacerbates the oxidative stress status of the pregnant women. Τo improve the oxidative stress status, several therapeutic interventions have been suggested. The aim of this network meta-analysis is to assess the effect of different dietary supplements on the oxidative stress status in pregnant women with GDM. METHODS: A network meta-analysis of randomized control trials was performed comparing the changes delta (Δ) in total antioxidant capacity (TAC) and concentration of malondialdehyde (MDA) as primary outcomes, following different therapeutic interventions with dietary supplements in pregnant women with GDM. Four electronic databases and grey literature sources were searched. The secondary outcomes were other markers of oxidative stress. RESULTS: The meta-analysis included 16 studies of 1173 women with GDM. Regarding ΔTAC: probiotics and omega-3 with vitamin E were superior to placebo/no intervention. Regarding ΔMDA: vitamin D with calcium, omega-3, vitamin D, omega-3 with vitamin E, magnesium with zinc and calcium, and probiotics were superior to placebo/no intervention. CONCLUSIONS: Administration of dietary supplements in women with GDM can be helpful in limiting the oxidative stress which develop in these pregnancies.

TGF-ß Physiology as a Novel Therapeutic Target Regarding Autoimmune Thyroid Diseases: Where Do We Stand and What to Expect.

Transforming growth factor beta (TGF-ß), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-ß, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-ß in thyroid autoimmunity. Suggested TGF-ß-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-ß can be used to bolster the inhibitory role of TGF-ß regarding the development of thyroid diseases, whereas anti-TGF-ß antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-ß biosynthesis and activation pathways. In conclusion, TGF-ß could evolve to a promising, novel therapeutic tool for thyroid autoimmunity.

Late diagnosis of 3ß-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene.

OBJECTIVES: 3ß-Hydroxysteroid dehydrogenase (3ß-HSD) deficiency is a rare type of congenital adrenal hyperplasia caused by recessive loss-of-function mutations in HSD3B2 gene. CASE PRESENTATION: We report an 8.5-year-old, 46XY, Roma boy with advanced adrenarche signs born to consanguineous parents. He was born at term with ambiguous genitalia. At 15 days of age, he underwent replacement therapy with hydrocortisone and fludrocortisone due to a salt wasting (SW) crisis and adrenal insufficiency. At 3.5 years, he was admitted again with SW crisis attributed to the low - unadjusted to body surface area - hydrocortisone dose and presented with bilateral gynecomastia and adrenarche. At 8.5 years, his bone age was four years more advanced than his chronological age and he was prepubertal, with very high testosterone levels. Gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis revealed the typical steroid metabolic fingerprint of 3ß-HSD deficiency. Sequencing of the HSD3B2 gene identified in homozygosity the novel p.Lys36Ter nonsense mutation. Furthermore, this patient was found to be heterozygous for p.Val281Leu in the CYP21A2 gene. Both parents were identified as carriers of the p.Lys36Ter in HSD3B2. CONCLUSIONS: A novel nonsense p.Lys36Ter mutation in HSD3B2 was identified in a male patient with hypospadias. 3ß-HSD deficiency due to mutations in the HSD3B2 gene is extremely rare and the finding of a patient with this rare type of disorders of sex development (DSD) is one of the very few reported to date. The complexity of such diseases requires a multidisciplinary team approach regarding the diagnosis and follow-up.

Assisted Reproduction in Congenital Adrenal Hyperplasia.

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders characterized by defects of adrenal steroidogenesis due to mutations in one of the following enzymes: 21-hydroxylase (21OH), 11ß-hydroxylase (11ßOH), 17α-hydroxylase (17OH; also known as 17, 20-lyase), 3ß hydroxysteroid dehydrogenase type 2 (3ßHSD2), steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and P450 oxidoreductase (POR). More than 95% of congenital adrenal hyperplasia cases are due to mutations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme (P450c21). This work focuses on this type of CAH given that it is the most frequent one. This disease is characterized by impaired cortisol and aldosterone production as well as androgen excess. A variant of the CAH is the non-classic type of CAH (NCCAH), usually asymptomatic before the 5th year of age, diagnosed during puberty especially in patients visiting a fertility clinic. NCCAH is characterized mainly by anovulatory cycles and/or high androgen concentrations. Both types of CAH are associated with infertility. Given that the incidence of NCCAH is greater than that of CAH, patients suffering from NCCAH are more often diagnosed for the first time in a fertility clinic. Thus, screening for NCCAH should always be considered. The causes of infertility in CAH patients are multi-factorial including virilization of external genitalia, altered psychosocial development, and hormonal disorders. The main challenges encountered in assisted reproduction are the androgen excess-associated anovulatory cycles as well as the increased circulating progesterone concentrations during the follicular phase which impact endometrial receptivity, tubal motility, and cervical thickness. Administration of sufficient substitution dose of glucocorticoids usually resolves these problems and leads not only to successful assisted reproduction treatment but also to spontaneous pregnancy. Patients with CAH should be followed by a multidisciplinary team including gynecologist, endocrinologist, and pediatrician.

In early pubertal boys, testosterone and LH are associated with improved anti-oxidation during an aerobic exercise bout.

PURPOSE: To investigate the association of the hypothalamic-pituitary-testicular (HPT) axis with pro- and anti- oxidation, in relation to puberty and obesity in boys, before and after an aerobic exercise bout. METHODS: This is a cross-sectional human observational study of 92 healthy normal-weight, obese pre- and early- pubertal boys that underwent a blood sampling, before, and after an aerobic exercise bout at 70% VO2max, until exhaustion. LH, FSH, total testosterone (tT) and markers of pro- (TBARS and PCs) and anti- (GSH, GSSG, GPX, catalase, TAC) oxidation were measured. RESULTS: Baseline LH, FSH, and tT concentrations were greater in early, than in pre- pubertal boys, independently of weight status. Post-exercise, LH concentrations decreased in early pubertal boys while FSH concentrations did not change in any of the studied groups. Baseline and post-exercise tT concentrations were lower in obese than in normal-weight early pubertal boys, while baseline and post-exercise LH and FSH concentrations did not differ between these groups. Post-exercise tT concentrations increased in early pubertal obese boys. Baseline LH, FSH and tT concentrations correlated positively with baseline anti-oxidation markers concentrations in pre-pubertal boys. Baseline tT concentrations correlated positively with the increase of TAC concentrations in early pubertal normal-weight boys. In all boys, baseline LH concentrations were the best positive predictors for the exercise-associated increase of TAC concentrations. CONCLUSIONS: It appears that the HPT axis maturation during puberty (in particular its LH and testosterone components) is positively associated with the increase of anti-oxidation during a bout of aerobic exercise.

The Beneficial Effect of the Mobile Application Euglyca in Children and Adolescents with Type 1 Diabetes Mellitus: A Randomized Controlled Trial.

Background: Euglyca® is a mobile application which we developed for children and adolescents suffering type 1 diabetes mellitus (T1DM) for calculation of the appropriate insulin bolus dose by importing in the equation carbohydrates, lipids, glucose levels, and personalized parameters. Aim of this study is to evaluate the efficacy of this application on patients' glycemic control and satisfaction. Subjects and Methods: Eighty children and adolescents (aged 13.5 ± 2.8 years old, mean ± standard deviation) with T1DM were included in the study and were randomly and equally assigned in two groups. Patients were asked to use Euglyca for the calculation of the bolus insulin dose in the E group and to pursue their routine calculations in the C group (controls). At baseline and at 3, 6, and 12 months following the initial visit, glycated hemoglobin (HbA1c) values, percentages of hypoglycemias, hyperglycemias, and normoglycemias were determined for each patient, while Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to assess patients' treatment satisfaction at baseline and at 6 and 12 months. Results: Children and adolescents in the E group had a statistically significant decrease in HbA1c values and increase in percentages of normoglycemias and DTSQ scores, in comparison to children and adolescents in the C group. In the E group, a statistically significant positive linear correlation was found between DTSQ score and percentages of normoglycemias and a statistically significant negative correlation between changes in percentages of normoglycemias (Δnormoglycemias) and changes in HbA1c (ΔHbA1c). Conclusions: The use of the mobile application Euglyca contributes to the improvement of glycemic control and treatment satisfaction of children and adolescents with T1DM.

Factors associated with poor adherence to vaccination against hepatitis viruses, streptococcus pneumoniae and seasonal influenza in HIV-infected adults.

INTRODUCTION: Vaccination against various pathogens is recommended for HIV positive adults. There are not sufficient data either on vaccination coverage of HIV positive adults or the risk factors associated with poor adherence to routine vaccination. PATIENTS-METHODS: During the period 2004-2014 vaccination coverage of a group of HIV infected adults against hepatitis A virus (HAV), hepatitis B virus (HBV), seasonal influenza virus and pneumococcal disease was recorded. Vaccination coverage was separated into two chronological periods, before and after 2010, as 2010 marks the start of the economic crisis in Greece. RESULTS: 1210 patients were included in our study. Vaccine coverage throughout the study for hepatitis B, hepatitis A, seasonal influenza and pneumococcal infection was 73.6%, 70.4%, 39% and 79%, respectively. The complete lack of insurance coverage was an independent factor of non-compliance in all proposed vaccines (vaccination against pneumococcal disease: OR: 0.82 95%CI: 0.49-1.35, vaccination against HBV: OR: 0.82, 95% CI: 0.45-1.49, vaccination against HAV OR: 0.54, 95%CI: 0.34-0.87, vaccination against influenza: OR: 1.27, 95% CI: 0.76-2.10). In addition, low educational level was associated with poor compliance to vaccination against pneumococcal disease, hepatitis A, hepatitis B, and influenza. Finally, the recommendation for vaccination after the onset of the economic crisis (2010) led to poor compliance to vaccination against HBV, HAV and pneumococcal disease, but not against influenza. CONCLUSIONS: In our study, vaccination coverage for vaccine-preventable diseases was found to be insufficient for HIV positive adults in Northern Greece. Also, low educational level, lack of insurance coverage and economic distress have contributed to poor vaccine compliance, leading to poor protection of the HIV positive population and decreased immune coverage in the community.

Novel FRET-substrates of Rhizomucor pusillus rennin: Activity and mechanistic studies.

The development of sensitive, easy and reliable methods for the determination of Rhizomucor pusillus rennin (MPR) activity, in free and in immobilized form, along with the elucidation of the mechanism of action, represent challenges for the widespread use of the enzyme in industrial cheese production. These could be accomplished by using highly specific and sensitive substrates, as well as direct assay methods. We designed and synthesized novel substrates based on Fluorescence Resonance Energy Transfer (FRET) for the MPR by employing computational simulation techniques and peptide synthesis in liquid phase. Three FRET-substrates (Abz-GFY-pNA, Abz-SFY-pNA and Abz-GFI-pNA) were found active, while the Abz-GFY-pNA showed the highest reliability, sensitivity and specificity among them. Subsequently, a novel mechanism of MPR action was elucidated, with the development of novel methods for assaying activity in free and immobilized form, which both may contribute in the wider use of rennin in cheese production and other biotechnological applications.

A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids.

INTRODUCTION: Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile. OBJECTIVE: To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children. METHODS: We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015). RESULTS: This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately. CONCLUSIONS: In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.