Strength, Elastic Properties and Fiber-Matrix Interaction Mechanism in Geopolymer Composites.

The current geopolymers have limited mechanical strength against the effect of tension, which makes them susceptible to brittle failure. However, owing to their potential as a sustainable construction material, there is growing interest in improving the poor mechanical properties of geopolymers. This study experimentally investigated crucial properties of polypropylene-fiber-reinforced fly ash-based geopolymer composites. The effects of polypropylene fibers (PPF) addition (0.5%, 1.0% and 1.5% by volume) on the mechanical properties of the geopolymer composites were investigated with respect to compressive and flexural strength, deformation behavior of Young's and shear moduli, and resilience capacity. In addition, scanning electron microscopy was performed to establish the morphology of the geopolymeric matrix and the fiber-matrix interfacial interaction. The addition of PPF significantly increased the flexural strength: compared with the control, at 7 days it was 27% greater for the 0.5% PPF composite and 65% greater for the 1.0% PPF composite. By 14 days it was 31% and 61% greater, respectively. By contrast, the 1.5% PPF composite had lower strength parameters compared with the control because the fiber dispersion increased the porosity. Similar trends were seen for resilience. The SEM observations showed the dispersion of the fibers and helped elucidate the fiber-matrix interaction mechanism.

No changes in adolescent's sedentary behaviour across Europe between 2002 and 2017.

BACKGROUND: Public health organizations have been alerted to the high levels of sedentary behaviour (SB) among adolescents as well as to the health and social consequences of excess sedentary time. However, SB changes of the European Union (EU) adolescents over time have not been reported yet. This study aimed to identify SB of the EU adolescents (15-17 years) in four-time points (2002, 2005, 2013 and 2017) and to analyse the prevalence of SB according to the sex. METHODS: SB of 2542 adolescents (1335 boys and 1207 girls) as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 using the Sport and Physical Activity EU Special Eurobarometers' data. SB was measured using the sitting time question from the short version of the International Physical Activity Questionnaire (IPAQ), such that 4h30min of daily sitting time was the delineating point to determine excess SB behaviour (≥4h30min of sitting time) or not (≤4h30min of sitting time). A χ2 test was used to compare the prevalence of SB between survey years. Furthermore, SB prevalence between sexes was analysed using a Z-Score test for two population proportions. RESULTS: The prevalence of SB among EU adolescents across each of the four survey years ranged from 74.2 and 76.8%, rates that are considered high. High levels of SB were also displayed by both sexes (girls: 76.8 to 81.2%; boys: 71.7 to 76.7%). No significant differences in the prevalence of SB among years (p > 0.05) were found for the whole sample, and for either girls or boys. Also, no significant differences in the prevalence of SB between girls and boys were found. CONCLUSION: The SB prevalence in European adolescents is extremely high (76.8% in 2017) with no differences between girls and boys. No significant improvements have been seen between 2002 and 2017. Eurobarometer should increase the adolescents' sample to make possible benchmarking comparisons among the EU countries and extend the survey to the younger children population.

High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis.

BACKGROUND: Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. METHODS: Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. RESULTS: Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (- 0.11 mmol/L), SBP (- 4.44 mmHg), DBP (- 3.60 mmHg), and WC (- 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (- 1.29 mmol/L). CONCLUSIONS: HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms.

Changes in sedentary behaviour in European Union adults between 2002 and 2017.

BACKGROUND: Sedentary behaviour (SB) has been identified as an important mortality risk factor. Health organizations have recognised SB as a public health challenge with major health, social, and economic consequences. Researchers have alerted the need to develop specific strategies, to monitor, prevent, and reduce SB. However, there is no systematic analysis of the SB changes in European Union adults. We aimed to examine SB changes between 2002 and 2017 in the European Union (EU) adult population. METHODS: SB prevalence (>4h30mins of sitting time/day) of 96,004 adults as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 of the Sport and Physical Activity EU Special Eurobarometers' data. The SB question of a modified version of the International Physical Activity Questionnaire was considered. SB prevalence between countries and within years was analysed with a χ2 test, and SB between genders was analysed with the Z-Score test for two population proportions. RESULTS: An association between the SB prevalence and the years was found (p < 0.001), with increases for the whole sample (2002: 49.3%, 48.5-50.0 95% confidence interval (CI); 2017: 54.5%, 53.9-55.0 95% CI) and men (2002: 51.2%, 50.0-52.4 95% CI; 2017: 55.8%, 55.0-56.7 95% CI) and women (2002: 47.6%, 46.6-48.7 95% CI; 2017: 53.4%, 52.6-54.1 95% CI) separately. The adjusted standardised residuals showed an increase in the observed prevalence versus the expected during 2013 and 2017 for the whole sample and women and during 2017 for men. For all years, differences were observed in the SB prevalence between countries for the whole sample, and men and women separately (p < 0.001). Besides, the SB prevalence was always higher in men versus women in the overall EU sample (p < 0.001). CONCLUSIONS: SB prevalence increased between 2002 and 2017 for the EU as a whole and for both sexes separately. Additionally, differences in SB prevalence were observed for all years between EU countries in the whole sample and both sexes separately. Lastly, SB was consistently higher in men than women. These findings reveal a limited impact of current policies and interventions to tackle SB at the EU population level.

Comparison of hip extension and rotation ranges of motion in young elite tennis players with and without history of low back pain.

BACKGROUND: Although low back pain (LBP) is known to be multi-factorial, certain studies have suggested that a deficit in hip extension and rotation range of motion (ROM) may be associated with LBP in athletes. OBJETIVE: The purpose of this study was to compare hip extension and rotation ROMs in elite tennis players with and without a history of LBP. METHODS: Forty-two male and 22 female young elite tennis players completed this study. Participants were divided into two groups: (1) 32 with history of LBP and (2) 32 without history of LBP. Descriptive measures of passive hip extension and rotation ROMs of the dominant and non-dominant limbs were taken. Active hip rotation ROMs were also assessed. Magnitude-based inferences on differences between groups and legs were made by standardizing differences. RESULTS: The inter-group statistical analysis reported no significant differences (p> 0.05; trivial effect with a probability higher than 95%; d⩽ 0.4) in any ROM measure analyzed. Further, neither LBP group nor control group reported significant bilateral or side-to-side differences (p> 0.05; trivial effect with a probability higher than 99%; d< 0.3) between legs regarding hip extension and rotation ROM measures. CONCLUSION: No relationship between hip extension and rotation ROM and history of LBP was found.

Different neuromuscular parameters influence dynamic balance in male and female football players.

PURPOSE: To analyse the relationship between several parameters of neuromuscular performance with unilateral dynamic balance measured through the Y-Balance test, as well as to determine the possible sex-related differences. METHODS: The Y-Balance test, isokinetic (concentric and eccentric) knee flexion and extension strength, isometric hip abduction and adduction strength, lower extremity joint range of motion (ROM) (hip, knee and ankle) and core stability were assessed in male (n = 88) and female (n = 44) professional football players. A stepwise multivariate linear least square regression with backward elimination analysis was carried out to identify a group of factors that were independently associated with balance performance in both sexes. RESULTS: Passive hip flexion and ankle dorsiflexion with knee flexed ROM were the main factors that retained a significant association to dominant (R2 = 23.1) and non-dominant (R2 = 33.5) balance scores for males. For females, core stability, hip abduction isometric peak torque, passive hip abduction and ankle dorsiflexion with knee flexed ROM variables retained a significant association with balance scores for both, dominant (R2 = 38.2) and non-dominant (R2 = 46.9) legs. CONCLUSIONS: Training interventions aimed at improving or maintaining unilateral dynamic balance in male football players should include, among other things, stretching exercises for the posterior chain of the lower extremity. However, females should also include exercises for strength and mobility of the hip abductors and core stability (especially in the frontal plane). This knowledge would allow clinicians and sport practitioners to develop more effective and tailored unilateral dynamic balance training interventions in male and female football players, possibly improving performance and reducing the risk of injury. LEVEL OF EVIDENCE: III.

Comparisons of hip strength and countermovement jump height in elite tennis players with and without acute history of groin injuries.

BACKGROUND: Despite the high groin-injury (GI) prevalence in tennis, no studies have assessed the extent to which intrinsic groin injury risk factors, such as hip muscle strength, have recovered in elite tennis players with a history of previous GI. OBJECTIVE: To investigate whether elite tennis players with a history of GI show differences in hip strength and jump height between injured and uninjured limbs and compared with dominant limb in tennis players without history of acute groin-injuries (NGI). DESIGN: Cohort study. PARTICIPANTS: Sixty-one tennis players completed this study: 17 in the GI group and 44 in the NGI. Isometric adductor and abductor hip strength were assessed with a handheld dynamometer, and unilateral counter-movement jump tests were performed on a contact mat connected to an Ergo tester. Paired t-tests were conducted to identify differences between injured and non-injured limbs in the GI group, and independent measures t-tests were conducted to compare between GI and NGI groups. RESULTS: Isometric adductor strength and adductor/abductor strength ratios were lower in the injured limb (16.4% and 20.1%, respectively) compared with uninjured side within the GI group, and lower than the dominant side in the NGI group. No significant differences were found for unilateral jump heights between sides in the GI, nor isometric abductor strength, when comparing GI to NGI groups. CONCLUSIONS: Isometric adductor weakness and adductor/abductor strength ratio deficits suggest that adductor muscle strength is not fully recovered in these athletes, potentially increasing their risk of a repeat groin injury.

Periprandial changes and effects of short- and long-term fasting on ghrelin, GOAT, and ghrelin receptors in goldfish (Carassius auratus).

The periprandial profile and effects of short- (7 days) and long-term (30 days) fasting on the ghrelinergic system were studied in goldfish (Carassius auratus). Plasma levels of acyl-ghrelin, desacyl-ghrelin, and ghrelin O-acyl transferase (GOAT) were analyzed by enzymoimmunoassays, and expression of preproghrelin, goat and growth hormone secretagogue receptors (ghs-r) was quantified by real-time PCR. Circulating levels of acyl-ghrelin and GOAT rise preprandially, supporting the role of acyl-ghrelin as a meal initiator in this teleost. Consistently, preproghrelin and ghs-r1a1 expression increases 1 h before feeding time in intestinal bulb, suggesting that this receptor subtype might be involved in the preprandial action of ghrelin in this tissue. Significant postfeeding variations are detected for preproghrelin in telencephalon, goat in telencephalon and hypothalamus, ghs-r1a1 in vagal lobe, ghs-r1a2 and ghs-r2a1 in hypothalamus and ghs-r2a2 in telencephalon and vagal lobe, especially in unfed fish. Short- and long-term fasting significantly increase preproghrelin expression in telencephalon and gut. Goat expression is upregulated by short-term fasting in telencephalon and hypothalamus, and by both short- and long-term fasting in gut. Expression of ghs-r increases by fasting in telencephalon, while an upregulation of type 2, but not type 1, receptors is observed in vagal lobe. In intestinal bulb, ghs-r1a2 transcripts increase after both short- and long-term fasting. These results show a high dependence of the ghrelinergic system on feeding and nutritional status in fish, and demonstrate for the first time a differential implication of the various components of this system suggesting different roles for the four ghrelinergic receptor subtypes.

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Two cholecystokinin receptor subtypes are identified in goldfish, being the CCKAR involved in the regulation of intestinal motility.

Cholecystokinin (CCK) plays a key role in the digestive physiology of vertebrates. However, very little is known about the role of CCK on intestinal functions in fish. The present study identifies two CCK receptor subtypes in a stomachless teleost, the goldfish (Carassius auratus), and investigates by using an in vitro system their involvement mediating the effects of the sulfated octapeptide of CCK (CCK-8S) on the motility of isolated proximal intestine. Partial-length mRNAs encoding two CCK receptor isoforms (CCKAR and CCKBR.I) were sequenced and the structural analysis showed that both receptors belong to the G-protein coupled receptor superfamily. Both goldfish CCK receptor sequences were more closely related to zebrafish sequences, sharing the lowest similarities with cavefish and tilapia. The highest expression of goldfish CCKAR was observed along the whole intestine whereas the CCKBR gen was predominantly expressed in the hypothalamus, vagal lobe and posterior intestine. Application of CCK-8S to the organ bath evoked a concentration-dependent contractile response in intestine strips. The contractions were not blocked by either tetrodotoxin or atropine, suggesting that CCK-8S acts on the gut smooth muscle directly. Preincubations of intestine strips with devazepide and L365,260 (CCKAR and CCKBR receptor selective antagonists) showed that the CCK-8S-induced contraction could be partially mediated by the CCKAR receptor subtype, which is also the most abundant CCK receptor found in gastrointestinal tissues. In conclusion, two CCK receptors with a differential distribution pattern has been identified in goldfish, and the CCKAR subtype is mainly involved in the regulation of intestinal motility by the CCK-8S.

New biological markers in the decision of treatment of head and neck cancer patients

Head and neck squamous cell carcinoma is the sixth most common cancer type worldwide. Also the 5-year survival rate of less than 50 % seems to be lower than other cancer types. There are some reasons behind this high mortality rate; one of them is the lack of knowledge about the biology and genomic instability behind the carcinogenic processes. These biological features could condition the failure of frontline treatment, in which case rescue treatment should be used, representing an overtreatment for the patients. For years many biological factors have been tested as prognostic and predictive factors in relation to treatment with a modest success. To find appropriate tests which could be used in the context of the individualized treatment decision, we have reviewed new biological markers, not only in tumor tissue, but also in normal tissue from head and neck carcinoma patients (AU)

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New biological markers in the decision of treatment of head and neck cancer patients.

Head and neck squamous cell carcinoma is the sixth most common cancer type worldwide. Also the 5-year survival rate of less than 50 % seems to be lower than other cancer types. There are some reasons behind this high mortality rate; one of them is the lack of knowledge about the biology and genomic instability behind the carcinogenic processes. These biological features could condition the failure of frontline treatment, in which case rescue treatment should be used, representing an overtreatment for the patients. For years many biological factors have been tested as prognostic and predictive factors in relation to treatment with a modest success. To find appropriate tests which could be used in the context of the individualized treatment decision, we have reviewed new biological markers, not only in tumor tissue, but also in normal tissue from head and neck carcinoma patients.

Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients.

BACKGROUND AND PURPOSE: A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. PATIENTS AND METHODS: Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ß value, a parameter defining RIA of lymphocytes, was calculated. RESULTS: Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ß values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ß values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). CONCLUSION: For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients.

Molecular biomarkers in the decision of treatment of cervical carcinoma patients

Cervical carcinoma is the third most common cancer in women worldwide. The programs developed for early detection have made that most patients are diagnosed in early stages. Treatment for those patients consists of conservative techniques as surgery or radical radiotherapy; however, the decision between those two therapies is still controversial. Even though in many cases this decision varies according to classical associated risk factors (i.e. tumor stage or age), in the clinical practice, a significant number of patients treated by surgery also receive post-surgery radiotherapy, with the consequent over-treatment and toxic effects. Since response to treatments is conditioned by individual factors, the use of new biological markers as novel predictive factors for both tumor and normal tissues could help clinicians to choose the best treatment schedule for each patient individually. Based on the experience of our institution, we have reviewed the new biological markers in cervical carcinoma patients treated by radiotherapy (AU)

The arylalkylamine-N-acetyltransferase (AANAT) acetylates dopamine in the digestive tract of goldfish: a role in intestinal motility.

Melatonin has been found in the digestive tract of many vertebrates. However, the enzymatic activity of the arylalkylamine-N-acetyltransferase (AANAT) and the hydroxindole-O-methyltransferase (HIOMT), the last two enzymes of melatonin biosynthesis, have been only measured in rat liver. Therefore, the first objective of the present study is to investigate the functionality of these enzymes in the liver and gut of goldfish, analyzing its possible daily changes and comparing its catalytic properties with those from the retina isoforms. The daily rhythms with nocturnal acrophases in retinal AANAT and HIOMT activities support their role in melatonin biosynthesis. In foregut AANAT activity also show a daily rhythm while in liver and hindgut significant but not rhythmic levels of AANAT activity are found. HIOMT activity is not detected in any of these peripheral tissues suggesting an alternative role for AANAT besides melatonin synthesis. The failure to detect functional HIOMT activity in both, liver and gut, led us to investigate other physiological substrates for the AANAT, as dopamine, searching alternative roles for this enzyme in the goldfish gut. Dopamine competes with tryptamine and inhibits retinal, intestinal and hepatic N-acetyltryptamine production, suggesting that the active isoform in gut is AANAT1. Besides, gut and liver produces N-acetyldopamine in presence of acetyl coenzyme-A and dopamine. This production is not abolished by the presence of folic acid (arylamine N-acetyltransferase inhibitor) in any studied tissue, but a total inhibition occurs in the presence of CoA-S-N-acetyltryptamine (AANAT inhibitor) in liver. Therefore, AANAT1 seems to be an important enzyme in the regulation of dopamine and N-acetyldopamine content in liver. Finally, for the first time in fish we found that dopamine, but not N-acetyldopamine, regulates the gut motility, underlying the broad physiological role of AANAT in the gut.

Molecular biomarkers in the decision of treatment of cervical carcinoma patients.

Cervical carcinoma is the third most common cancer in women worldwide. The programs developed for early detection have made that most patients are diagnosed in early stages. Treatment for those patients consists of conservative techniques as surgery or radical radiotherapy; however, the decision between those two therapies is still controversial. Even though in many cases this decision varies according to classical associated risk factors (i.e. tumor stage or age), in the clinical practice, a significant number of patients treated by surgery also receive post-surgery radiotherapy, with the consequent over-treatment and toxic effects. Since response to treatments is conditioned by individual factors, the use of new biological markers as novel predictive factors for both tumor and normal tissues could help clinicians to choose the best treatment schedule for each patient individually. Based on the experience of our institution, we have reviewed the new biological markers in cervical carcinoma patients treated by radiotherapy.

Plasminogen activator inhibitor-1 (PAI-1) expression in relation to hypoxia and oncoproteins in clinical cervical tumors.

PURPOSE: Explore the role of plasminogen activator inhibitor-1 (PAI-1) in cervical cancer and its relationship to hypoxia and the expression of p53, Ku70/80, and cyclin D1. MATERIAL AND METHODS: The expression of PAI-1, cyclin D1, and p53, together with tumor oxygenation, were determined in 43 consecutive patients suffering from localized cervical carcinoma. Oncoprotein expression was determined by immunohistochemistry. Tumor oxygenation was measured using a polarographic probe system, "pO2 histography." RESULTS: PAI expression was considered negative in 32.6% and overexpressed in 18.6% of cases. Cyclin D1 showed a median expression of 5.0 (range 0-70). We observed a positive association between PAI expression and altered p53 (p = 0.049) and cyclin D1 (p = 0.020). An inverse association was detected between PAI and Ku70/80 expression (p = 0.042). Cyclin D1 staining increased according to tumor volume (r = 0.314, p = 0.009). We did not observe a significant association between PAI and hypoxia or other clinicopathological parameters. CONCLUSION: The present results show that PAI-1 overexpression is associated with nonhomologous end-joining DNA repair down-regulation (low Ku70/80 expression) and with increased p53 and cyclin D1 expression, and they suggest that PAI-1 plays a role in the tumor behavior in cervical carcinoma.

Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

OBJECTIVES: The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. METHODS: The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). RESULTS: Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. CONCLUSION: Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

Balance of pro-apoptotic transforming growth factor-beta and anti-apoptotic insulin effects in the control of cell death in the postnatal mouse retina.

Transforming growth factor (TGF)-beta and insulin display opposite effects in regulating programmed cell death during vertebrate retina development; the former induces apoptosis while the latter prevents it. In the present study we investigated coordinated actions of TGF-beta and insulin in an organotypic culture system of early postnatal mouse retina. Addition of exogenous TGF-beta resulted in a significant increase in cell death whereas exogenous insulin attenuated apoptosis and was capable of blocking TGF-beta-induced apoptosis. This effect appeared to be modulated via insulin-induced transcriptional down-regulation of TGF-beta receptor II levels. The analysis of downstream signalling molecules also revealed opposite effects of both factors; insulin provided survival signalling by increasing the level of anti-apoptotic Bcl-2 protein expression and phosphorylation and down-regulating caspase 3 activity whereas pro-apoptotic TGF-beta signalling reduced Bcl-2 mRNA levels and Bcl-2 phosphorylation and induced the expression of TGF-induced immediate-early gene (TIEG), a Krüppel-like zinc-finger transcription factor, mimicking TGF-beta activity.