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Summary In 27 centres across Europe, the prevalence of deforming spinal Scheuermann’s disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann’s, helping the differential diagnosis from osteoporosis. Introduction This study aims to assess the prevalence of Scheuermann’s disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. Methods In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann’s disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl’s node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2–L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann’s by alternative published algorithms when these used the radiographic signs we assessed. Results Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann’s varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann’s was not associated with BMD of the spine or hip. Conclusions Since most of the variation in population impact of Scheuermann’s was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

To study the association between vertebral deformities and subjective health outcome indicators, including back pain and disability, a cross-sectional survey with spinal radiographs and personal interviews was carried out in 36 study centres in 19 European countries on a total of 15,570 men and women aged 50-79 years (population-based stratified random samples). No interventions were done. The main outcome measures were the presence and intensity of current and previous back pain, functional capacity (ADL questionnaire) and overall subjective health. The presence and intensity of back pain and functional and health impairments varied within wide ranges with no obvious regional pattern. However, the associations between negative health outcomes and vertebral deformity were homogeneous between countries and between centres within countries. In logistic regression analyses weak but significant associations between the presence of vertebral deformities and various health indicators were demonstrated. The magnitude of the associations increased with severity and number of deformities. Compared with subjects without deformities those with low-grade deformities had no or only a weakly elevated risk for back pain, disability and impaired subjective health (odds ratios (OR) 1.2-1.3). The odds ratios increased for individuals with single severe deformities (OR 1.3-2.1) and were highest in those with multiple severe deformities (OR 1.7-4.2). The associations between vertebral deformities and negative health outcomes were stronger in men than in women. In this cross-sectional study radiologically assessed vertebral deformities were therefore weakly associated with both current and previous back pain as well as with functional and health impairments in both women and men. Multiple severe deformities were associated with severe and disabling back pain with stronger effects in men.

The aim of this study was to determine whether variation in the level of selected hormonal and reproductive variables might explain variation in the occurrence of vertebral deformity across Europe. A population-based cross-sectional survey method was used. A total of 7530 women aged 50-79 years and over were recruited from 30 European centres. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs which were taken according to a standard protocol. After adjusting for age, centre, body mass index and smoking, those in the highest quintile of menarche (age 2=16 years) had an increased risk of vertebral deformity (odds ratio [OR]=1.48; 95% confidence interval [CI] 1.16, 1.88). Increased menopausal age (>52.5 years) was associated with a reduced risk of deformity (OR=0.78; 95% CI 0.60, 1.00), while use of the oral contraceptive pill was also protective (OR=0.76; 95% CI 0.58, 0.99). There was a smaller protective effect associated with one or more years use of hormone replacement therapy, though the confidence limits clearly embraced unity. There was no apparent effect of parity or breast-feeding on the risk of deformity. We conclude that oestrogen status is an important determinant of vertebral deformity. Ever use of the oral contraceptive pill was associated with a 25% reduction in risk of deformity though the effect may be a result of the higher-dosage oestrogen pills used in the past. Parity and breast-feeding do not appear to be important and would appear to have little potential for identification of women at high risk of vertebral deformity.[PUBLICATION ABSTRACT]

The influence of alcohol consumption on the risk of osteoporosis is not well established. The aim of this study was to determine the relationship between frequency of alcohol consumption and the risk of vertebral deformity across different European populations. A population survey method was used. Men and women aged 50 years and over were recruited from population-based sampling frames in 36 centres from 19 European countries. Subjects were invited to attend by letter of invitation for an interviewer-administered questionnaire and lateral spinal radiographs. Vertebral deformity was defined morphometrically using the McCloskey-Kanis method. Data from 14 237 individuals were available for this analysis. Alcohol consumption was compared between the 809 men and 884 women with vertebral deformity and the 5905 men and 6639 women without vertebral deformity. The frequency of alcohol intake was greater in men than women. Overall, there was no detectable association between frequency of alcohol intake and vertebral deformity in either men or women. Stratification by age showed that women 65 years and over who took alcohol on more than 5 days per week had a reduced risk of vertebral deformity compared with those taking alcohol less than once per week. This protection was most obvious after adjusting for age, centre, body mass index, smoking, current level of physical activity and previous fractures (odds ratio [OR]=0.65; 95% confidence intervals [CI]=0.43, 0.99). There was a smaller and non-significant protective effect amongst men aged 65 years and over and this was most apparent amongst moderately frequent drinkers (1-4 days per week) (OR=0.81; 95% CI=0.62, 1.08). There was no association between the occurrence of vertebral deformity and frequency of alcohol consumption in younger men and women. Overall, the effects of the frequency of alcohol consumption on vertebral deformity were modest. In older women, regular consumption on more than 5 days per week is associated with a reduced risk. Further, prospective data are required to confirm these findings. It is also necessary to investigate, in terms of amount of alcohol consumed, at what level the benefits of regular intake are obviated by the increased risks from alcohol excess.[PUBLICATION ABSTRACT]

A pharmacophore model for inhibitors of Escherichia coli’s DNA Gyrase B was developed, using computer-aided drug design. Subsequently, docking studies showed that 2,5(6)-substituted benzimidazole derivatives are promising molecules, as they possess key hydrogen bond donor/acceptor groups for an efficient interaction with this bacterial target. Furthermore, 5(6)-bromo-2-(2-nitrophenyl)-1H-benzimidazole, selected as a core molecule, was prepared on a multi-gram scale through condensation of 4-bromo-1,2-diaminobenzene with 2-nitrobenzaldehyde using a sustainable approach. The challenging functionalization of the 5(6)-position was carried out via palladium-catalyzed Suzuki–Miyaura and Buchwald-Hartwig amination cross-coupling reactions between N-protected-5-bromo-2-nitrophenyl-benzimidazole and aryl boronic acids or sulfonylanilines, with yields up to 81%. The final designed molecules (2-(aminophen-2-yl)-5(6)-substituted-1H-benzimidazoles), which encompass the appropriate functional groups in the 5(6)-position according to the pharmacophore model, were obtained in yields up to 91% after acid-mediated N-boc deprotection followed by Pd-catalyzed hydrogenation. These groups are predicted to favor interactions with DNA gyrase B residues Asn46, Asp73, and Asp173, aiming to promote an inhibitory effect.

Introduction: Different implant–abutment connections have been developed to reduce mechanical and biological failure. The most frequent complications are loss of preload, screw loosening, abutment or implant fracture, deformations at the different interfaces, and bacterial microleakage. Aim: To review the evidence indicating whether the implant–abutment connection type is significant regarding the following issues: (1) maintenance of the preload in static and dynamic in vitro studies; (2) assessment of possible deformations at the implant–abutment interfaces, after repeated application of the tightening torque; (3) evaluation of the sealing capability of different implant connections against microleakage. Materials and Methods: In June 2020, an electronic literature search was performed in Medline, EBSCO host, and PubMed databases. The search was focused on the ability of different implant connections to maintain preload, resist deformation after tightening and retightening, and prevent microleakage. The related titles and abstracts available in English were screened, and the articles that fulfilled the inclusion criteria were selected for full-text reading. Results: The literature search conducted for this review initially resulted in 68 articles, among which 19 articles and 1 systematic review fulfilled the criteria for inclusion. The studies were divided according to the three proposed objectives, with some studies falling into more than one category (maintenance of preload, surface abutment–implant deformation, and resistance to microleakage). Conclusions: Conical abutment appears to result in fewer mechanical complications, such as screw loosening or fractures, and higher torque preservation. After SEM evaluation, damage was observed in the threads of the abutment screws, before and after loading in internal and external connections. Internal hexagon implants and predominantly internal conical (Morse taper) implants showed less microleakage in dynamic loading conditions. We suggest further studies to guarantee excellence in methodological quality.

The objective was to estimate the contribution of experience, body size and maturity status to variation in the functional capacities of adolescent football (soccer) players. The sample included 69 players 13.2-15.1 years of age from three clubs which competed in the highest division for their age group in the first Portuguese national division. Height and weight were measured and stage of pubic hair development was assessed at clinical examination. The number of years of experience in football was obtained at interview. Three tests of functional capacity were administered: 30-m dash (running speed), vertical jump (explosive power) and a yo-yo intermittent endurance test (aerobic resistance). Multiple linear regression analysis was used to estimate the relative contributions of age, stage of sexual maturity, height, weight and years of formal training in football to the three indicators of functional capacity. Stage of puberty, body size and years of training accounted for 21% to 50% of the variance in the three tasks. Sexual maturity status was the primary contributor to the variance in the intermittent shuttle run, whereas weight and height were the primary contributors to the explained variance in the 30-m dash and vertical jump, respectively. In conclusion, biological maturity status significantly influences the functional capacity of adolescent football players 13-15 years of age. Training is a significant contributor to aerobic resistance, whereas weight and height are significant contributors to the sprint and vertical jump, respectively.

Closed-loop neuronal stimulation has a strong therapeutic potential for neurological disorders such as Parkinson’s disease. However, at the moment, standard stimulation protocols rely on continuous open-loop stimulation and the design of adaptive controllers is an active field of research. Delayed feedback control (DFC), a popular method used to control chaotic systems, has been proposed as a closed-loop technique for desynchronisation of neuronal populations but, so far, was only tested in computational studies. We implement DFC for the first time in neuronal populations and access its efficacy in disrupting unwanted neuronal oscillations. To analyse in detail the performance of this activity control algorithm, we used specialised in vitro platforms with high spatiotemporal monitoring/stimulating capabilities. We show that the conventional DFC in fact worsens the neuronal population oscillatory behaviour, which was never reported before. Conversely, we present an improved control algorithm, adaptive DFC (aDFC), which monitors the ongoing oscillation periodicity and self-tunes accordingly. aDFC effectively disrupts collective neuronal oscillations restoring a more physiological state. Overall, these results support aDFC as a better candidate for therapeutic closed-loop brain stimulation.

Objective: To evaluate the growth, maturity status and functional capacity of youth soccer players grouped by level of skill. Subjects: The sample included 69 male players aged 13.2–15.1 years from clubs that competed in the highest division for their age group. Methods: Height and body mass of players were measured and stage of pubic hair (PH) was assessed at clinical examination. Years of experience in football were obtained at interview. Three tests of functional capacity were administered: dash, vertical jump and endurance shuttle run. Performances on six soccer-specific tests were converted to a composite score which was used to classify players into quintiles of skill. Multiple analysis of covariance, controlling for age, was used to test differences among skill groups in experience, growth status and functional capacity, whereas multiple linear regression analysis was used to estimate the relative contributions of age, years of training in soccer, stage of PH, height, body mass, the height×weight interaction and functional capacities to the composite skill score. Results: The skill groups differed significantly in the intermittent endurance run (p<0.05) but not in the other variables. Only the difference between the highest and lowest skill groups in the endurance shuttle run was significant. Most players in the highest (12 of 14) and high (11 of 14) skill groups were in stages PH 4 and PH 5. Pubertal status and height accounted for 21% of the variance in the skill score; adding aerobic resistance to the regression increased the variance in skill accounted for to 29%. In both regressions, the coefficient for height was negative. Conclusion: Adolescent soccer players aged 13–15 years classified by skill do not differ in age, experience, body size, speed and power, but differ in aerobic endurance, specifically at the extremes of skill. Stage of puberty and aerobic resistance (positive coefficients) and height (negative coefficient) are significant predictors of soccer skill (29% of the total explained variance), highlighting the inter-relationship of growth, maturity and functional characteristics of youth soccer players.

Background: Lipoprotein(a) (Lp(a)) is a plasma lipoprotein with atherogenic, prothrombotic, and proinflammatory properties. Elevated Lp(a) levels are linked to the development of early atherosclerosis in childhood and contribute to a higher risk of cardiovascular disease (CVD) in adulthood.Purpose: This study aimed to assess the clinical significance of Lp(a) levels in Portuguese pediatric patients who underwent serum Lp(a) testing as part of a lipid disorder screening prompted by obesity, hypercholesterolemia, and/or a family history of premature CVD. We also evaluated the correlation between Lp(a) levels and CVD risk factors.Methods: This cross-sectional retrospective study included 792 pediatric patients. Data on demographics, clinical history, body mass index, and laboratory values, including Lp(a), were collected. Lp(a) levels were categorized into 3 groups: <75 nmol/L, 75–125 nmol/L, and >125 nmol/L. A multivariate analysis was used to identify factors associated with Lp(a) ≥ 75 nmol/L.Results: The most prevalent comorbidities in this sample were obesity and associated low-grade inflammation, each affecting at least one-third of participants. The median Lp(a) level was 31.80 nmol/L, with 9.1% and 21.6% of children having intermediate (75–125 nmol/L) and high (>125 nmol/L) Lp(a) levels, respectively. Higher total cholesterol, non–high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels were correlated with elevated Lp(a) levels. The multivariate analysis identified an elevated LDL-C level as a predictor of a higher Lp(a) level.Conclusion: This study highlights the alarming prevalence of elevated Lp(a) levels in Portuguese pediatric patients who underwent serum Lp(a) testing due to lipid disorder screening, with >30% at intermediate/high CVD risk. As Lp(a) levels are mostly genetically determined and tend to persist into adulthood, these findings emphasize the importance of including Lp(a) screening in the cardiovascular risk assessment of children with CVD risk factors to enable timely prevention strategies for adultonset CVD.