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Lockdown resulting from the pandemic led to a change in the health habits of the computer workers community. Sedentary work, together with less active lifestyles, aggravated by the COVID-19 pandemic leads to impacts on physical activity (PA) and can contribute to the development of musculoskeletal symptoms (MSS). Aim(s): Understand the effects of lockdown on the perception of physical activity levels and on the perception of frequency of musculoskeletal symptoms, over periods of 12 months and 7 days, in computer workers. Methods: Longitudinal comparative study between 2019 (M1) and 2021 (M2), over 18 months, in 40 volunteer participants. The inclusion criteria were full-time workers aged between 18 and 65 and the exclusion criteria included diagnosis of non-work-related medical conditions. In addition to a socio-demographic questionnaire, the Nordic musculoskeletal questionnaire (NMQ) was used to evaluate the MSS and the International Physical Activity Questionnaire (IPAQ), was used to analyse the perception of the level of PA. These questionnaires were used in two assessment stages (M1 and M2). McNemar test and Wilcoxon paired test were used to evaluate the effect of lockdown on the perception of PA, and on the perception of frequency of musculoskeletal symptoms. Results: The MSS prevalence in the previous 12 months increased significantly in the neck (M1: 45.0%, M2: 62.5%, p = 0.046), in the shoulders (M1: 37.5%, M2: 55.0%, p = 0.033), and in the hands/wrists (M1: 25.0%, M2: 45.0%, p = 0.019). The mean pain score increased in the shoulders (1.43 ? 2.24, 2.35 ? 2.55, p = 0.003) and in the elbows (0.18 ? 0.59, 0.60 ? 1.34, p = 0.015). No differences were found in the PA between M1 and M2, but the weekly mean sitting time increased from 4.75 ? 2.26 to 6.26 ? 2.65 (p < 0.001). Conclusion: After 18 months it became clear that MSS perception increased mainly in the neck, shoulders and hands/wrists with a significant increase in pain intensity in the shoulder and elbow regions. The weekly sitting time increased significantly. Further studies are needed in order to determine the impact of teleworking in a pandemic context. But multifactor behind these results should be taken into account by health institutions and those responsible for the Prevention of Occupational Risks in Computer Workers in order to adopt educational strategies for the promotion of Physical activity (PA), in these workers. DA10-CEBF-4D75 | Maria Salom? Martins Ferreira N/A

Computer workers’ sedentary work, together with less active lifestyles, aggravated by the COVID-19 pandemic, represents a high risk for many chronic diseases, leading to a decrease in health-related quality of life (QoL). Workplace exercises consist of a set of physical exercises, implemented during work breaks, that have multiple benefits for workers’ health. Aim: To assess the impact of online workplace exercises on computer workers’ perception of quality of life. Methods: Quasi-experimental study with two groups: a control group (n = 26) and an intervention group (n = 13). The inclusion criteria were that participants must be aged between 18 and 65 years old and the exclusion criteria included diagnosis of non-work-related medical conditions. The interventions consisted of workplace exercises, which were applied for 17 consecutive weeks, each session lasting 15 min, three times a week. The exercise programme, performed online and guided by a physiotherapist, consisted of mobility exercises, flexibility and strength exercises, with the help of a TheraBand® for elastic resistance. The control group were not subjected to any intervention. A socio-demographic questionnaire and the Health Survey Questionnaire (SF-36v2) were used in two assessment stages (M0—baseline and M1—final of intervention). A mixed ANOVA with interaction time*group was used to evaluate the effect of the exercise programme. Results: A good perception of the QoL was obtained in both stages. The exercise programme had a positive effect in the domains of Pain (ptime*group = 0.012, η2p = 0.158), Physical Function (ptime*group = 0.078, η2p = 0.082), Physical Performance (ptime*group = 0.052, η2p = 0.098), and Emotional Performance (ptime*group = 0.128, η2p = 0.061). Conclusion: After 17 weeks of workplace exercises, it became clear that the intervention group positively increased their QoL perception, with this improvement being significant in the Pain domain, which resulted in an improvement in their health condition. Therefore, further studies are needed to determine the optimal exercise for CWs, with detailed exercise types, different intensities and focused on various health conditions.

Computer work has assumed a very important role for many companies, but specific occupational and health symptoms associated with the use of computers can appear. According to the literature, physical activity is considered a key player in the prevention and control of work-related musculoskeletal symptoms, contributing to a better quality of life in computer workers. The principal aims of this review are to contribute to a better understanding of the relationship among sedentary behavior, physical activity and quality of life of computer workers; to outline the importance of promoting the development of an educational program for Occupational Health directed at computer workers at the level of quality of life, musculoskeletal symptoms, and physical activity; and to call for attention to the factors needed to initiate and maintain a health program that involves the active participation of workers who must be concerned about their health. This review demonstrates the important role of workplaces in health promotion and the opportunities that workplaces provide to establish and continue successful health-promotion programs for computer workers, generating important benefits for the health and quality of life of individuals and groups. DA10-CEBF-4D75 | Maria Salom? Martins Ferreira N/A

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease. Several pharmacological and surgical therapies have been developed; however, they are accompanied by some adverse effects. As a result, many patients have been resorting to complementary medicine, namely acupuncture, in the hope of obtaining symptomatic improvements without having disruptive side effects. Therefore, advances in research in this area are very important. This work presents a systematic review of the effectiveness of acupuncture treatments in relieving PD symptoms. Methods: EMBASE, Medline, Pubmed, Science Direct, The Cochrane Library, Cochrane Central Register of Controlled Trials (Central) and Scielo databases, were systematically searched from January 2011 through July 2021. Randomised controlled trials (RCTs) published in English with all types of acupuncture treatment were included. The selection and analysis of the articles was conducted by two blinding authors through Rayyan application. Results: A total of 720 potentially relevant articles were identified; 52 RCTs met our inclusion criteria. After the exclusion of 35 articles, we found 17 eligible. The included RCTs reported positive effects for acupuncture plus conventional treatment compared with conventional treatment alone in the UPDRS score. Conclusions: Although all the studies reviewed pointed out a positive effect of acupuncture on improving motor and non-motor symptoms in Parkinson’s disease, we found great discrepancies regarding the studies’ design and methodology, making difficult any comparison between them.

(1) Background: Human polycystic ovary/ovarian syndrome (PCOS) is linked to endocrine, metabolic, and psychological complications. We propose a randomized controlled pilot study for an acupuncture protocol regarding the management of PCOS symptoms based on TCM diagnosis; (2) Methods: We will randomly allocate 120 women diagnosed with PCOS into two groups. The study group will be treated with acupuncture for points known to act upon the autonomous regulation of the hormonal, metabolic and emotional components. (3) Results and Conclusions: We expect to provide evidence of high methodological quality related to the effects and safety of an acupuncture protocol based on the perspective of a TCM diagnostic.

Background: Hypericum perforatum (HP) is currently one of the most consumed medicinal plants in the world. In traditional Chinese medicine, the herb hypericum (Guan Ye Lian Qiao) belongs to the group of plants that clarify heat. It is also used to treat various types of infection and inflammation. In contrast to the extensive literature on the antidepressant effects of HP, little is known about its action on platelets. The main objective of this work was to investigate the possible relevance of HP to platelet function. Methods: We characterized the profile of platelet activation in the presence of HP extracts through an evaluation of molecular markers by flow cytometry: mobilization of intracellular Ca++ and expression of platelet receptors such as activated GPIIbIIIa and P-selectin (CD62). Results: The results indicated a possible inhibitory effect of HP on the platelet activation response, which could be explained by the effect on intracellular calcium mobilization and the expression of activated GPIIbIIIa receptors. Despite of the limitations of an in vitro study, our results provide evidence of the possible mechanisms of action of HP. Conclusions: Further studies are needed to elucidate the effect of HP on hemostasis, but it may be recognized as a substance with antiplatelet properties., This research was funded by Cooperativa de Ensino Superior Politécnico e Universitário-CESPU, crl (Portugal), grant number PAEHP_CESPU_2017.

A lack of physical activity in computer workers (CW) can contribute to the development of musculoskeletal symptoms (MSS). Aim: (i) Evaluate MSS over a 12 month and 7 days period, (ii) determine physical activity (PA) levels and compliance with World Health Organization (WHO) PA recommendations, and (iii) assess the relationship between compliance with WHO PA recommendations and MSS. A cross-sectional observational study comprising 119 computer workers. The Nordic Musculoskeletal Questionnaire (NMQ) was used to evaluate the MSS and the International Physical Activity Questionnaire (IPAQ) was used to analyse the perception of the level of PA. MSS occurred in the lumbar region (56.3%), neck (43.7%), and shoulders (39.5%). 44.7% of the participants reported a low level of PA. The percentage of compliance was similar among women and men (62.2% vs. 58.5%, respectively). Negative correlations were found between pain intensity and metabolic equivalent values. The participants who followed the WHO PA recommendations reported a lower frequency of MSS compared to those who did not, but the differences were not statistically significant. It was possible to conclude that computer workers presented a higher frequency of MSS in the lower back, neck, and shoulders. Regarding the level of PA, participants were mostly classified as low. Participants who followed the WHO PA recommendations reported lower MSS than those who did not. This finding could be important in obtaining successful programs that promote health-oriented physical activity in this group of workers.

A lack of physical activity in computer workers (CW) can contribute to the development of musculoskeletal symptoms (MSS). Aim: (i) Evaluate MSS over a 12 month and 7 days period, (ii) determine physical activity (PA) levels and compliance with World Health Organization (WHO) PA recommendations, and (iii) assess the relationship between compliance with WHO PA recommendations and MSS. Methods: A cross-sectional observational study comprising 119 computer workers. The Nordic Musculoskeletal Questionnaire (NMQ) was used to evaluate the MSS and the International Physical Activity Questionnaire (IPAQ) was used to analyse the perception of the level of PA. Results: MSS occurred in the lumbar region (56.3%), neck (43.7%), and shoulders (39.5%). 44.7% of the participants reported a low level of PA. The percentage of compliance was similar among women and men (62.2% vs. 58.5%, respectively). Negative correlations were found between pain intensity and metabolic equivalent values. The participants who followed the WHO PA recommendations reported a lower frequency of MSS compared to those who did not, but the differences were not statistically significant. Conclusion: It was possible to conclude that computer workers presented a higher frequency of MSS in the lower back, neck, and shoulders. Regarding the level of PA, participants were mostly classified as low. Participants who followed the WHO PA recommendations reported lower MSS than those who did not. This finding could be important in obtaining successful programs that promote health-oriented physical activity in this group of workers.

Leukocyte and platelet rich fibrin (L-PRF) is one of the platelet concentrates used to support regeneration and healing process. Many studies showed possible immunological and antibacterial properties of L-PRF. We perform an in vitro study to analyze the effect of L-PRF on platelet activation, platelet-leukocytes interactions and antimicrobial activity, important components in the healing process. Molecular biomarkers related with platelet activation and platelet-leukocyte interactions were analyzed by means of flow cytometry when L-PRF exudate was added to whole blood platelets. L-PRF membrane was used to evaluate antimicrobial activity using Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853) and Candida albicans (ATCC 90028). Our experimental design allows to evaluate platelet activation and analyze molecular biomarkers of other immune cells and platelet-leukocyte interactions. From the results obtained we can conclude that L-PRF can be a valuable tool in healing process, efficient in activating platelets of whole blood and inhibiting microbial growth. In our opinion, the use of L-PRF exudate, in addition to L-PRF membrane, presents some advantages that have to be considered in clinical trials. Additional research on the characterization and quantification of cells and its products present in the L-PRF exudate, as well as on the temporal factor released. Also, further studies using strains isolated from clinical cases are needed.

Introduction Balance and gait disorders are relevant symptoms in the quality of life of Parkinson's patients. Currently, there is no therapy to reverse or treat this condition. Acupuncture treatment is believed to improve motor ability through the cortico-basal-thalamus-cortical-ganglia. Aim To investigate qualitatively the acute effect of acupuncture on balance and gait in Parkinson's disease in 7 patients. Methods This is a randomized and controlled crossover study. The same individual patient was part of both, experimental (real acupuncture) and control group (false acupuncture/sham), and the sequence was randomized. Balance and gait parameters were measured at two different moments, before and after treatment, using four force platforms as well as the collection of 3D markers positions taken by 11 cameras. Images were analyzed using Qualisys Track Manager software that let us extract data related to the quality of gait and balance. Results Statistically significant differences were found in gait speed (p = 0.016), gait cadence (p = 0.006), support base width (p = 0.0001), medio-lateral oscillation (p = 0.017), left-right step length (p = 0.0002), and stride length: right-right (p = 0.0000) and left-left (p = 0.0018), time of left support phase (p = 0.029), right support phase (p = 0.025) and double support phase (p = 0.015), between the initial and final moments for the experimental group. Differences in right-left stride length were found for both groups. Conclusion Our results suggest that the acupuncture protocol used objectively could improve gait in Parkinson disease patients. A deep research involving a statistical evaluation supported on a larger number of voluntaries should be accomplished to confirming these promising preliminary results.

Endothelial and platelet dysfunction increase the atherothrombotic risk in diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an important complication in diabetes mellitus. In the present work, type 2 diabetic patients were classified by a podiatrist into presence or absence of arterial ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak sequence of GPIbα may be associated with a higher risk of developing arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment., The authors thank the ‘‘Sociedade Portuguesa de Esclerose Multipla’’ (SPEM) and ‘‘Associac¸a˜o Nacional de Esclerose Mu´ltipla’’ (ANEM) for their collaboration. This research was partially financed by Portuguese Funds through FCT—Fundac¸a˜o para a Cieˆncia e a Tecnologia, within the Project PEstOE/MAT/UI0013/2017., info:eu-repo/semantics/publishedVersion

Introduction: We examined the potential role of polymorphisms of the platelet genes GP1BA (rs2243093, rs6065 and VNTR), ITGB3 (rs5918), ITGA2 (rs938043469) and P2RY12 (rs2046934, rs6801273 and rs6798347) as risk factors for myocardial infarction (MI). Methods: The study population was divided into three groups: controls (n=235), MI at age ≤45 years (MI ≤45, n=44), and MI at age >45 years (MI >45, n=78). The control group was further divided into two subgroups (control ≤45 and >45), and subgroups including only men were also considered for statistical analysis. Polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Regarding non-genetic risk factors, the control group differed statistically from the MI ≤45 group (p45 group (p45 was compared with the control group, with a higher risk of MI in the TT genotype (OR 2.852; 95% CI: 1.092-7.451; p=0.032). In the GP1BA rs6065 polymorphism, a statistically significant difference was found between control ≤45 only men and MI ≤45 only men, with a higher risk in the CT genotype (OR 5.568; 95% CI: 1.421-21.822; p=0.016), despite the low numbers included. The other polymorphisms studied did not show any statistically significant correlations. Conclusion: There is a statistically significant association between the TT genotype of the ITGA2 rs938043469 polymorphism and increased risk for MI >45. Resumo: Introdução: Determinou-se o papel de polimorfismos dos genes de expressão plaquetária GP1BA (rs2243093, rs6065 e o VNTR p.Ser415_Thr428(0_4)), ITGB3 (rs5918), ITGA2 (rs938043469) e P2RY12 (rs2046934, rs6801273 e rs6798347) como fatores de risco para o enfarte agudo do miocárdio (EAM). Métodos: A amostra foi dividida em três grupos: Controlo (n=235), EAM ≤45 anos (n=44) e EAM >45 anos (n=78). O grupo Controlo foi ainda dividido em dois subgrupos (Controlo ≤45 e >45). Subgrupos incluindo somente homens também foram considerados para fins estatísticos. Os polimorfismos foram estudados através de PCR e RFLP. Resultados: Em relação aos fatores de risco não genéticos, o grupo Controlo diferia estatisticamente do grupo EAM ≤ 45 anos (p45 anos (p45 anos e Controlo, associando-se o genótipo TT a aumento de risco de EAM (OR 2,852; IC 95% de 1,092 a 7,451; p=0,032). No polimorfismo rs6065 do gene GP1BA foi encontrada uma diferença estatística quando comparados os grupos Controlo ≤ 45 só homens e EAM ≤ 45 só homens, associando-se o genótipo C/T a um maior risco de EAM (OR 5,568; IC 95% de 1,421 a 21,822; p=0,016), apesar do baixo n. Os outros polimorfismos não apresentaram correlação significativa. Conclusão: Existe uma associação estatística significativa entre o genótipo T/T do polimorfismo rs938043469 do gene ITGA2 e o risco de EAM >45. Keywords: Myocardial infarction and platelet polymorphisms, GPIb-V-IX, GPIa-IIa, GPIIb-IIIa: ADP P2Y12 receptor, Palavras-chave: Enfarte agudo do miocárdio e polimorfismos plaquetários, GP Ib-V-IX, GP Ia-IIa, GP IIb-IIIa, ADP P2Y12 receptor

Angiotensin II receptor blockers (ARBs) are a new class of drugs for the treatment of hypertension. In this study, we studied the potential genotoxic effects of five ARBs in vivo and in vitro in human peripheral blood lymphocytes (PBLs) by means of the cytokinesis-block micronucleous (CBMN) assay in combination with fluorescence in situ hybridization (FISH) with a centromeric probe. The nuclear division index (NDI) was used as a measure of cytotoxicity. We also analyzed the association between sex, age, duration of treatment and MN formation. The in vivo study was carried out in 55 hypertensive patients. The in vitro study was performed in 10 control individuals by adding the drugs to the culture medium at a final concentration similar to the levels found in plasma in patients. Our results showed a significant increase in the frequencies of MN and binucleated cells with MN (BNMN) in vivo and especially in vitro. We observed variability in the mean frequency of MN and BNMN among the five drugs analyzed. In vivo, patients treated with Candesartan, Telmisartan and Valsartan showed a statistical significant increase in these parameters, while Olmesartan showed the highest effect in vitro. We also found that the drugs inhibit the NDI in vitro and that Eprosartan, Olmesartan and Telmisartan are the ARBs studied with the highest effect in decreasing the proliferation of the cells. FISH analysis revealed no significant difference between patients and controls in the frequency of centromeric signals. A slight variability, without statistical significance, in the frequency of micronuclei with a centromere signal (CN(+)MN) was found among the different ARBs analyzed, ruling out an aneugenic potential. When accounting for risk factors, we found that in patients there is a positive correlation between MN, BNMN and sex and a negative correlation with duration of treatment.

Introduction Neck pain is considered a musculoskeletal disease with a prevalence of 30% to 50% in western populations. Its impact on quality of life is high and the efficacy of conventional treatments limited. Korean hand acupuncture (KHA), based on the theory that the hand is a microsystem of the human body, has the advantage to be easy to perform without side effects to the patient, having therapeutic and diagnosis value. The aim of the study was to investigate the effect of KHA on nonspecific neck pain. Methods A randomized controlled trial was conducted involving 31 patients with cervicalgia. The experimental (EG) (verum) and control (CG) (sham) groups were subject to KHA in the corresponding neck area of the hand (true KHA) and anterior thigh somatotopy (sham KHA), respectively. Before (T0) and after a 20 min’ session of KHA (T1), intensity of pain and motion range of the most painful neck movement were measured. Results After treatment, statistically significant differences between the experimental and control groups were observed in both the intensity of pain (measured with a visual analogue scale); and in the percentage in the range of motion (assessed by a goniometer), (p = 0.005, and p = 0.005 respectively). Conclusions Our preliminary data seems to be sufficiently relevant to recommend further studies on the effects of Korean hand acupuncture on neck pain although limitations as the sample size, the methods to assess neck mobility and the assessment of the cumulative therapeutic effect have to be taken into account.

Introduction and objectives: We studied genotypic and allelic frequencies of polymorphisms that can affect platelet function, namely the Kozak, VNTR and HPA-2 polymorphisms of glycoprotein Ibα, the PlA polymorphism of glycoprotein IIIa and the C807T polymorphism of glycoprotein Ia, in a Portuguese population composed of 227 donors. Methods: PCR-RFLP was used to assess the Kozak, HPA-2, PlA and C807T polymorphisms. The VNTR polymorphism was discriminated by different weight bands on electrophoresis. Results: All genotypic frequencies were in Hardy-Weinberg equilibrium and do not differ from other Caucasian populations. Genotypic frequencies were 68.3%, 26.9% and 4.8% for PlA1/A1, PlA1/A2 and PlA2/A2 genotypes of the PlA polymorphism, 79.3%, 20.3% and 0.4% for TT, TC and CC genotypes of the Kozak polymorphism, 81.1%, 18.9% and 0.0% for aa, ab and bb genotypes of the HPA-2 polymorphism, 15.4%, 0.9%, 70.5%, 11.5%, 1.3% and 0.4% for BC, BD, CC, CD, DD and CE genotypes of the VNTR polymorphism, and 39.7%, 50.2% and 10.1% for CC, CT and TT genotypes of the C807T polymorphism. Conclusions: The Portuguese population has now been characterized in terms of major platelet glycoprotein polymorphisms, which will be an important tool for further studies to assess the role of platelet glycoproteins in individual predisposition to prothrombotic conditions and response to antithrombotic therapy. Resumo: Introdução e objetivos: Neste estudo determinámos as frequências alélicas e genotípicas de 5 polimorfismos que poderão afetar a funcionalidade plaquetária, nomeadamente os polimorfismos Kozak, VNTR e HPA-2 da glicoproteína Ibα, o polimorfismo PlA da glicoproteína IIIa e o polimorfismo C807T da glicoproteína Ia numa população portuguesa constituída por 227 dadores voluntários. Métodos: A técnica de PCR-RFLP foi usada para determinar os polimorfismos Kozak, HPA-2, PlA e C807T. O polimorfismo VNTR foi discriminado através do padrão eletroforético criado por bandas de peso molecular diferente. Resultados: As frequências genotípicas encontram-se dentro do equilíbrio de Hardy-Weinberg e não diferem estatisticamente de outras populações caucasianas. As frequências genotípicas encontradas foram 68,3, 26,9 e 4,8% para os genótipos PlA1/A1, PlA1/A2 e PlA2/A2 do polimorfismo PlA, 79,3, 20,3 e 0,4% para os genótipos TT, TC e CC do polimorfismo Kozak, 81,1, 18,9 e 0,0% para os genótipos aa, ab e bb do polimorfismo HPA-2, 15,4, 0,9, 70,5, 11,5, 1,3 e 0,4% para os genótipos BC, BD, CC, CD, DD e CE do polimorfismo VNTR, e 39,7, 50,2 e 10,1% para os genótipos CC, CT e TT do polimorfismo C807T. Conclusões: A população portuguesa encontra-se, assim, caracterizada no que respeita aos polimorfismos das principais glicoproteínas plaquetárias, o que poderá servir como ferramenta importante de estudos futuros que avaliem o papel das glicoproteínas plaquetárias na predisposição individual a condições pró-trombóticas e resposta à terapia antitrombótica. Keywords: Platelet glycoprotein polymorphisms, Glycoprotein Ib-IX-V, Glycoprotein Ia-IIa, Glycoprotein IIb-IIIa, Palavras-chave: Polimorfismos das glicoproteínas plaquetárias, Glicoproteína Ib-IX-V, Glicoproteína Ia-IIa, Glicoproteína IIb-IIIa

Menopause is a period of women's life characterized by the cessation of menses in a definitive way. The mean age for menopause is approximately 51 years. Primary ovarian insufficiency (POI) refers to ovarian dysfunction defined as irregular menses and elevated gonadotrophin levels before or at the age of 40 years. The etiology of POI is unknown but several genes have been reported as being of significance. The fragile X mental retardation 1 gene (FMR1) is one of the most important genes associated with POI. The FMR1 gene contains a highly polymorphic CGG repeat in the 5 untranslated region of exon 1. Four allelic forms have been defined with respect to CGG repeat length and instability during transmission. Normal (5-44 CGG) alleles are usually transmitted from parent to offspring in a stable manner. The full mutation form consists of over 200 repeats, which induces hypermethylation of the FMR1 gene promoter and the subsequent silencing of the gene, associated with Fragile X Syndrome (FXS). Finally, FMR1 intermediate (45-54 CGG) and premutation (55-200 CGG) alleles have been principally associated with two phenotypes, fragile X tremor ataxia syndrome (FXTAS) and fragile X primary ovarian insufficiency (FXPOI). This work was supported by the Vice-rectorate for Research of the University of the Basque Country, Bilbao, Spain.

© 2016 Elsevier Inc. All rights reserved., Involvement of soluble CD40 ligand (sCD40L) in thrombosis and inflammation on the context of coronary artery disease is currently being revised. In that perspective, we had studied the association of sCD40L with markers of platelet activation and markers of endothelial and vascular function. On that cohort, a stratification of patients with acute myocardial infarction (AMI) 1 month after percutaneous coronary intervention (PCI) was observed based on concentrations of sCD40L. The study intended to identify the groups of AMI patients with different profiles of sCD40L concentrations and verify how medication, clinical evolution, biochemical data, and markers of regulation of endothelial function at genetic (endothelial nitric oxide synthase polymorphisms) and post-transcriptional levels (circulating microRNAs) affect sCD40L serum levels. Lower quartiles of sCD40L (,2.3 ng/mL) were associated with higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high frequency of G894T polymorphism, and altered expression of a set of microRNAs assumed to be involved in the regulation of endothelial and cardiac function and myocardium hypertrophy, relative to patients in sCD40L upper quartiles. A characteristic sCD40L variation pattern in STEMI patients was identified. Low levels of sCD40L 1 month after PCI distinguish STEMI patients with worse prognosis, a compromised cardiac healing, and a persistent endothelial dysfunction, as given by the association between sCD40L, NT-proBNP, G894T polymorphism, and specific profile of miRNA expression. These results suggest sCD40L could have a prognostic value in STEMI patients., The work was financially supported by Fundação para a Ciência e Tecnologia (SFRM/BPD/6308/2009 and UID/BIO/04565/2013) and Liga dos Amigos do Hospital de Santa Marta.

Summary Fragile X Syndrome (FXS, MIM 309550) is mainly due to the expansion of a CGG trinucleotide repeat sequence, found in the 5′ untranslated region of the FMR1 gene. Some studies suggest that stable markers, such as single nucleotide polymorphisms (SNPs) and the study of populations with genetic identity, could provide a distinct advance to investigate the origin of CGG repeat instability. In this study, seven SNPs (WEX28 rs17312728:G>T, WEX70 rs45631657:C>T, WEX1 rs10521868:A>C, ATL1 rs4949:A>G, FMRb rs25707:A>G, WEX17 rs12010481:C>T and WEX10 ss71651741:C>T) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28-T, WEX70-C, WEX1-C, ATL1-G, and WEX10-C are preferably associated with cis-acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of “susceptible” alleles and (2) association between “susceptible” alleles and STR and SNP haplotypes. These results may indicate that, in Arratia, SNP status does not identify a pool of susceptible alleles, as it does in Markina. In Arratia valley, the SNP haplotype association reveals also a potential new “protective” factor.

The antihypertensive drug atenolol was found to induce chromosome loss, detected as micronuclei in the peripheral lymphocytes of treated patients. The fundamental question which chromosomes the micronuclei were derived from remains to be answered. Analysis of structural chromosomal aberrations (CAs) and expression of fragile sites (FS) were pursued in this study. They revealed a significantly higher incidence of chromosomal aberrations (chromatid and chromosome breaks) in patients compared with controls, where 10 FS emerged as specific. Also, the band 17q12-21, where known fragile sites have not been reported, was only expressed in atenolol-treated patients. Fluorescence in situ hybridization using chromosome-specific probes revealed the preferential involvement of chromosomes 7, 11, 17 and X in the micronuclei (MN) of patients. The results also suggest a correlation between chromosomal fragility and content of MN, and support the findings for a linkage between hypertension and a locus on chromosome 17.

Fragile X syndrome is the most common form of inherited mental retardation. The molecular basis is usually the unstable expansion of a CGG repeat in the FMR1 gene. We previously analyzed a sample of two Basque valleys. In the present work we extend the study to another five isolated valleys. The results show that differences in factors implicated in CGG repeat instability—CGG repeat size, XS548/FRAXAC1 haplotypes, and AGG interspersion pattern—are present in the Basque populations analyzed.

The aim of the present study was to assess if the presence of survivin mRNA in exfoliated cells present in urine samples can be a reliable marker of the presence of bladder tumour and recurrence. Urine samples from 30 patients with superficial urothelial cell carcinomas (UCC) were collected prior to transurethral resection (TUR) of the tumour and in the first routine follow-up, three months after TUR. Detection of survivin mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). No correlation was observed between survivin detection and the clinico-pathological variables analysed, nevertheless, when patients were grouped into low-grade (G1) and high-grade (G2+G3) tumours, statistically significant differences were found between both groups (p=0.04). When we analysed the results of survivin detection and urinary cytology together, we observed that informative cases rose from 27.8% to 44.4%. Also, Kaplan-Meier curves for patients with negative cytology in the first follow-up, categorised according to survivin detection, revealed that survivin mRNA positive cases recurred earlier than negative ones. From our results we can conclude that detection of survivin expression can be a reliable tumour marker, but more studies are needed to clarify the potential of survivin to predict recurrences. These results showed that survivin detection in combination with conventional urinary cytology can be a useful tool to increase the sensitivity in detecting the presence of a recurrence after TUR.

© 2015 Elsevier Inc. All rights reserved., Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction., The work was financially supported by Fundação para a Ciência e Tencnologia (SFRM/BPD/6308/2009) and by Liga dos Amigos do Hospital de Santa Marta.

The expansion of a trinucleotide repeat [CGG]n located in the FMR1 X-linked gene is the main cause of fragile X syndrome, the most common form of inherited mental retardation. We have analyzed the factors known, to date, to influence the instability of the repeat in 158 normal X chromosomes from the Spanish Basque population. These factors included length of the repeat, AGG interspersion pattern, length of uninterrupted CGG and DXS548-FRAXAC1 markers associated haplotype. Previous investigations on Basques showed an absence of this disorder among mentally retarded individuals that was likely due to a low prevalence of large CGG alleles and the presence of AGG interruptions on them. The present report suggests that, although the frequency of large alleles is low and they do maintain AGG interruptions, different mutational pathways that might lead to fragile X syndrome could be occurring among Basques. These pathways mainly include alleles with internal sequences 9 + 9 + n and 9 + 12 + 9 that show fragile X associated haplotypes. Besides, the lack of the most proximal AGG interruption, proposed recently as a novel factor involved in CGG repeat instability, was highly identified among alleles with long pure CGG tracts, which showed an internal sequence n + 9. The data suggest that, despite the lower incidence of large alleles, the prevalence of potentially unstable alleles among Basques is similar to that of other Caucasian populations and that these alleles could become fragile X chromosomes.

Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki-67 immunoexpression in low-grade (GI-II) USPC in order to predict the potential outcome of these tumors. P53 and Ki-67 immunoexpression were studied in function of recurrence-free and progression-free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki-67 index (≥18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression-free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki-67 index into the risk model, single pTa/T1-GI Ki-67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1-G1 with a high risk of recurrence and progression. Ki-67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low-grade USPC, the accuracy of the prognostic discrimination is enhanced. © 2003 Wiley-Liss, Inc.

Numerous studies have shown there is consistent evidence implicating genetic factors in the etiology of autism. In some cases chromosomal abnormalities have been identified. One type of these abnormalities is gaps and breaks nonrandomly located in chromosomes, denominated fragile sites (FS). We cytogenetically analyzed a group of autistic individuals and a normal population, and we examined the FS found in both samples with the aim of (1) comparing their FS expression, (2) ascertaining whether any FS could be associated with our autistic sample, and (3) examining if there are differences between individual and pooled-data analyses. Different statistical methods were used to analyse the FS of pooled and individual data. Our results show that there are statistically significant differences in the spontaneous expression of breakages between patients and controls, with a minimal sex difference. Using the method for pooled data, eight autosomal FS have preferential expression in patients and five patients were found to be positive at FS Xq27.3. With the method per-individual analysis, four FS emerged as specific in our autistic sample. Inferences of FS from pooled data were different from those of individual data. The findings suggest that although analysis of pooled data is necessitated by the problem of sparse data, analysis of single individuals is essential to know the significance of FS in autism.

Premature ovarian failure (POF) is defined as cessation of menses before the age of 40. The most significant single gene associated with POF is the Fragile X Mental Retardation 1 gene (FMR1). In the present work we screened women with fertility problems from the Basque Country in order to determine, whether in these women, FMR1 CGG repeat size in the intermediate and premutation range was associated with their pathology, and whether intermediate and premutation carriers had endocrine signs of diminished ovarian function, using the most established measure of ovarian reserve, the gonadotropin FSH. A patient sample of 41 women with ovarian insufficiency and a control sample of 32 women with no fertility problems from the Basque Country were examined. The patient sample was classified into three categories according to the results of the retrospective assessment of their ovarian function. In group 2 of patients, women with irregular cycles, reduced fecundity and FSH levels ≥ 10IU/l, there is a significant increase in the number of intermediate and premutation FMR1 alleles (35-54 CGG repeats). In group 3 of patients, women with amenorrhea for at least four consecutive months and FSH levels ≥ 10IU/l, a significant increase in the number of intermediate FMR1 alleles (35-54 CGG repeats) was found in patients compared with controls. In this group all the patients had a serum concentration > 40 IU/l. The results suggest that in the analysed Basque sample the FMR1 gene has a role in the aetiology of POF. However, elevated FSH levels are more related to the menstrual cycle pattern than to the CGG repeat size.

The cytogenetic study of a nodal metastasis from a gastric carcinoma, after two passages in nude mice, revealed a large number of double minutes. Comparative genomic in situ hybridization (CGH) analysis using DNA extracted from this xenograft revealed the existence of three clear amplification units that originated from the chromosomal subregions 6q24–25, 7q31–32, and 8q24 in the xenograft DNA. Similar, though less prominent, CGH results were found with DNAs extracted from the primary tumor and its metastasis, implying that the same amplicons were also present, albeit less abundantly, in the DNAs of these neoplastic tissues. Southern analysis of the second-passage xenograft detected 18- and 10-manifold amplification of MET (located at 7q31) and MYC (located at 8q24), respectively. The retrospective study of the first passage of the xenograft, as well as of the metastatic and primary tumors before xenografting, showed amplification levels of MET of, respectively, 12-, 9-, and 5-fold and MYC of, respectively, 8-, 7-, and 5-fold. Our results suggest that increased levels of co-amplification of MYC and MET correlate with enhanced growth potential in this case of gastric carcinoma.

Fragile X Syndrome (FXS, MIM 309550) is mainly due to the expansion of a CGG trinucleotide repeat sequence, found in the 5' untranslated region of the FMR1 gene. Some studies suggest that stable markers, such as single nucleotide polymorphisms (SNPs) and the study of populations with genetic identity, could provide a distinct advance to investigate the origin of CGG repeat instability. In this study, seven SNPs (WEX28 rs17312728:GT, WEX70 rs45631657:CT, WEX1 rs10521868:AC, ATL1 rs4949:AG, FMRb rs25707:AG, WEX17 rs12010481:CT and WEX10 ss71651741:CT) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28-T, WEX70-C, WEX1-C, ATL1-G, and WEX10-C are preferably associated with cis-acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of "susceptible" alleles and (2) association between "susceptible" alleles and STR and SNP haplotypes. These results may indicate that, in Arratia, SNP status does not identify a pool of susceptible alleles, as it does in Markina. In Arratia valley, the SNP haplotype association reveals also a potential new "protective" factor.

Background and Aims: Pyrethroids (PYRs) Pesticides are synthesized from prototype pyrethrins (naturally occurring toxin) derived from the flowers of Tanacetum cinerariaefolium, in order to increase...

Fragile X Syndrome (FXS) is associated with an unstable CGG repeat sequence in the 5’ untranslated region in the first exon of the FMR1 gene which resides at chromosome position Xq27.3 and is coincident with the fragile site FRAXA. The CGG sequence is polymorphic with respect to size and purity of the repeat. Interpopulation variation in the polymorphism of the FMR1 gene and consequently, in the predisposition to FXS due to the prevalence of certain unstable alleles has been observed. Spanish Basque population is distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. We had previously reported preliminary data on the existence of FMR1 allele differences between two Basque valleys (Markina and Arratia). In the present work we extended the study to Uribe, Gernika, Durango, Goierri and Larraun, another five isolated valleys enclosing the whole area within the Spanish Basque region. We analyzed the prevalence of FMR1 premutated and intermediate/grey zone alleles. With the aim to complete the previous investigation about the stability of the Fragile X CGG repeat in Basque valleys, we also analyzed the existence of potentially unstable alleles, not only in relation with size and purity of CGG repeat but also in relation with DXS548 and FRAXAC1 haplotypes implicated in repeat instability. The data show that differences in allele frequencies as well as in the distribution of the mutational pathways previously identified are present among Basques. The data also suggest that compared with the analyzed Basque valleys, Gernika had increased frequency of susceptibility to instability alleles, although the prevalence of premutation and intermediate/grey zone alleles in all the analyzed valleys was lower than that reported in Caucasian populations.

The expansion of a trinucleotide repeat [CGG]n located in the FMR1 X-linked gene is the main cause of fragile X syndrome, the most common form of inherited mental retardation. We have analyzed the factors known, to date, to influence the instability of the repeat in 158 normal X chromosomes from the Spanish Basque population. These factors included length of the repeat, AGG interspersion pattern, length of uninterrupted CGG and DXS548-FRAXAC1 markers associated haplotype. Previous investigations on Basques showed an absence of this disorder among mentally retarded individuals that was likely due to a low prevalence of large CGG alleles and the presence of AGG interruptions on them. The present report suggests that, although the frequency of large alleles is low and they do maintain AGG interruptions, different mutational pathways that might lead to fragile X syndrome could be occurring among Basques. These pathways mainly include alleles with internal sequences 9 + 9 + n and 9 + 12 + 9 that show fragile X associated haplotypes. Besides, the lack of the most proximal AGG interruption, proposed recently as a novel factor involved in CGG repeat instability, was highly identified among alleles with long pure CGG tracts, which showed an internal sequence n + 9. The data suggest that, despite the lower incidence of large alleles, the prevalence of potentially unstable alleles among Basques is similar to that of other Caucasian populations and that these alleles could become fragile X chromosomes.

Approximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki-67 immunoexpression in low-grade (GI-II) USPC in order to predict the potential outcome of these tumors. P53 and Ki-67 immunoexpression were studied in function of recurrence-free and progression-free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki-67 index (/=18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression-free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki-67 index into the risk model, single pTa/T1-GI Ki-67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1-G1 with a high risk of recurrence and progression. Ki-67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low-grade USPC, the accuracy of the prognostic discrimination is enhanced.

Aims: Cell-cycle regulatory proteins are important indicators in determining progression trough the cell-cycle and progression to invasive cancer in patients presenting with superficial bladder cancer. We performed an immunohistochemical study in order to evaluate the prognostic value of the expression of p16, p27, pRb, p53 and Ki-67 in superficial grade I and II papillary urothelial cell carcinoma of the bladder. Methods: p16, p27, p53, pRb and Ki-67 immunoexpression was studied in 14 pTa, 35 pT1a and 7 pT1b bladder tumours at presentation and at recurrence of their tumours. The recurrence-free survival and the progression-free survival were analysed according to these regulatory cell-cycle proteins expression. Results: For survival in univariate analysis a high Ki-67 labelling index was a poor prognostic factor for recurrence-free and progression-free survival ( P =0.0014 and P =0.012, respectively). Ki-67 labelling index was also an independent recurrence-free survival prognostic factor ( P =0.0005). The p16, p27, p53 and pRb immunoreactivity was not significantly associated with recurrence or progression rate in this group of bladder carcinomas. Conclusions: These data suggest that the Ki-67 labelling index can be a reliable marker in predicting recurrence and/or progression in superficial low-grade bladder carcinomas and may be relevant in planning adjuvant therapy.

Numerous studies have shown there is consistent evidence implicating genetic factors in the etiology of autism. In some cases chromosomal abnormalities have been identified. One type of these abnormalities is gaps and breaks nonrandomly located in chromosomes, denominated fragile sites (FS). We cytogenetically analyzed a group of autistic individuals and a normal population, and we examined the FS found in both samples with the aim of (1) comparing their FS expression, (2) ascertaining whether any FS could be associated with our autistic sample, and (3) examining if there are differences between individual and pooled-data analyses. Different statistical methods were used to analyse the FS of pooled and individual data. Our results show that there are statistically significant differences in the spontaneous expression of breakages between patients and controls, with a minimal sex difference. Using the method for pooled data, eight autosomal FS have preferential expression in patients and five patients were found to be positive at FS Xq27.3. With the method per-individual analysis, four FS emerged as specific in our autistic sample. Inferences of FS from pooled data were different from those of individual data. The findings suggest that although analysis of pooled data is necessitated by the problem of sparse data, analysis of single individuals is essential to know the significance of FS in autism.

A case of partial trisomy 2(q21q33) detected by cordocentesis at 27 weeks' gestation in a polymalformed fetus is described. This is the second case of a prenatally detected de novo duplication of 2q and the first involving the region referred to above.

The aim of this work was a study of the genotoxic potential with fluorescence in situ hybridization (FISH) with centromereof chronic long-term therapy with the antihypertensive specific DNA probes allows discrimination between MN due drug nimodipine by measures of sister chromatid exchanges to fragments (clastogenic damage) and MN containing whole (SCE) and micronuclei (MN) in peripheral human lympho- chromosomes (chromosome loss), since the presence of a cytes of patients with long-term exposure to this drug. hybridization signal in a MN is a direct measure of the presence Peripheral human lymphocytes of control individuals of a centromere (Eastmond et al., 1995; Zijno et al., 1996; exposed in vitro to nimodipine were also studied to assess the Tucker et al., 1997). This methodology is being increasingly effect of the drug itself. Fluorescence in situ hybridization used in monitoring studies (Ramo ´rez et al., 1997; Migliore (FISH) with a centromeric probe was performed to deter- et al., 1999a; Thierens et al., 1999; Andrianopoulos et al., mine the origin of the induced MN. The in vivo study 2000; Touil et al., 2000). was carried out on five patients under antihypertensive Sister chromatid exchanges (SCE) are events that involve treatment with nimodipine. The in vitro study was per- breaks in both chromatids of a single chromosome, at formed on five control individuals by adding the drug to coincident locations, with subsequent interchange and repair the culture medium at a final concentration similar to the (Latt et al., 1981). SCE have been evaluated in numerous levels found in plasma (controls/medium). The in vivo study studies involving human exposure to therapeutic compounds showed no genotoxic effects of long-term therapy with (Sarto et al., 1990; Awara et al., 1998; Migliore et al., 1998; nimodipine because the frequencies of SCE and MN in Lanza et al., 1999; Ahmad et al., 2000; Pilger et al., 2000).