Different acquisition systems for heart rate variability analysis may lead to diverse outcomes.

Heart rate variability (HRV) is a relevant physiological variable for the estimation of cardiac autonomic function. Although the gold standard for HRV registration is the electrocardiogram (ECG), several applications (APPs) have been increasingly developed. The evaluation carried out by these devices must be compatible with ECG standards. The aim of this study was to compare the data obtained simultaneously with ECG and APP with chest heart rate transmitters. Fifty-six healthy individuals (28 men and 28 women) were evaluated at rest through a short simultaneous HRV measurement with both devices. Data from both acquisition systems were analyzed separately using their own analysis software and exported and analyzed using a validated software. Signal recordings were compatible between the two acquisition systems (Pearson r=0.99; P<0.0001). Although a high correlation was found for the HRV variables obtained in the time domain (Spearman r=0.99; P<0.0001), the correlation decreased in the frequency domain (Pearson r=0.85; P<0.0001) when two software programs were used. Comparison of the averages of spectral analysis parameters also showed differences when HRV data were analyzed separately in each device for low-frequency (LF) and high-frequency (HF) bands. Although the portability of these mobile devices allows for optimal HRV evaluation, the direct analysis obtained from these devices must be carefully evaluated with respect to frequency domain parameters.

Different acquisition systems for heart rate variability analysis may lead to diverse outcomes

Heart rate variability (HRV) is a relevant physiological variable for the estimation of cardiac autonomic function. Although the gold standard for HRV registration is the electrocardiogram (ECG), several applications (APPs) have been increasingly developed. The evaluation carried out by these devices must be compatible with ECG standards. The aim of this study was to compare the data obtained simultaneously with ECG and APP with chest heart rate transmitters. Fifty-six healthy individuals (28 men and 28 women) were evaluated at rest through a short simultaneous HRV measurement with both devices. Data from both acquisition systems were analyzed separately using their own analysis software and exported and analyzed using a validated software. Signal recordings were compatible between the two acquisition systems (Pearson r=0.99; P<0.0001). Although a high correlation was found for the HRV variables obtained in the time domain (Spearman r=0.99; P<0.0001), the correlation decreased in the frequency domain (Pearson r=0.85; P<0.0001) when two software programs were used. Comparison of the averages of spectral analysis parameters also showed differences when HRV data were analyzed separately in each device for low-frequency (LF) and high-frequency (HF) bands. Although the portability of these mobile devices allows for optimal HRV evaluation, the direct analysis obtained from these devices must be carefully evaluated with respect to frequency domain parameters.

Does Quorum Sensing play a role in microbial shifts along spontaneous fermentation of cocoa beans? An in silico perspective.

Cocoa fermentation is a spontaneous process shaped by a variable microbial ecosystem which is assembled due to cross-feeding relationship among yeasts and bacteria, resulting in a synchronized microbial succession started by yeasts, followed by lactic acid bacteria (LAB) and finalized by acetic acid bacteria (AAB). Several studies have indicated the effect of microbial interactions in food ecosystems highlighting the importance of quorum sensing (QS) in bacterial adaptation in harsh environments modulating several phenotypes such as biofilm formation, tolerance to acid stress, bacteriocin production, competence, morphological modifications, motility, among others. However, antagonic interactions also occur, and can be marked by Quorum Quenching (QQ) activity, negatively impacting QS regulated phenotypes. Our current knowledge regarding microbial cocoa composition and functioning is based on culture-based analysis and culture-independent PCR-based methods. Therefore, we set out to investigate the application of metagenomics analysis on a classical spontaneous cocoa fermentation in order to describe: (I) the microbial taxonomic composition; (II) the functional potential of the cocoa microbiome; (III) the microbiome putative QS potential; and (IV) the microbiome QQ potential. Both aims III and IV are related to the expression of effectors that may confer advantageous traits along fermentation which can explain their dominance in specific time zones during the entire process. We have observed a bacterial succession shaped by yeasts and filamentous fungi and then Enterobacteriaceales, LAB and AAB, as well as a diverse genetic metabolic potential related to proteins and carbohydrates metabolism associated to the yeast Saccharomyces cerevisiae and members of the Enterobacteriaceales order and LAB and AAB groups. In addition, in silico evidences of interspecific QS arsenal were found in members of the genera Enterobacter, Lactobacillus, Bacillus and Pantoea, while inferences of intraspecific QS potential were found in the members of the genera Bacillus, Enterobacter, Komagataeibacter, Lactobacillus and Pantoea. In addition, a QQ potential was detected in Lactobacillus and in AAB members. These findings indicate that QS and QQ may modulate bacterial dominance in different time points during fermentation, along with cross-feeding, being responsible for their maintenance in a large time range.

Correction to: Bone metabolism in patients with anorexia nervosa and amenorrhoea.

Unfortunately, the sixth author name was incorrectly spelled as "S. Fassio" instead of "A. Fassio" in the original publication.

Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.

Bone metabolism in patients with anorexia nervosa and amenorrhoea.

PURPOSE: Aim of this study is focusing on bone metabolism in AN patients with amenorrhoea and related estrogen deficiency effects. METHODS: AN patients were compared both with healthy females and with postmenopausal women (reference model for estrogen deficiency). The study sample included 81 females with AN. Laboratory tests [25-OH vitamin D, bone turnover markers, intact parathyroid hormone, sclerostin (SOST) and dickkopf-related protein (DKK1)] and dual energy X-ray absorptiometry (DXA) were taken into account. RESULTS: AN patients had higher levels of C-terminal telopeptide of type I collagen (CTX) than both control groups. AN adolescents had CTX higher than AN young adults. In postmenopausal women, intact N-propeptide of type I collagen was higher if compared with each other group. In AN groups, Dickkopf-related protein 1 was significantly lower than the two control groups. No differences were found in sclerostin except in adolescents. In AN adolescents, DXA values at femoral sites were higher than in AN young adults and a positive correlation was found with body weight (p < 0.01) and with fat mass evaluated using DXA (p < 0.01). CONCLUSIONS: AN women with amenorrhoea have an increased bone resorption like postmenopausal women but bone formation is depressed. The consequent remodeling uncoupling is considerably more severe than that occurring after menopause.

Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.

The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts.

Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts with the Cdc42 GTPase activating protein CdGAP, a GAP for Rac1 and Cdc42, at cell-cell contacts. CdGAP recruitment to junctions does not require Ajuba; rather Ajuba seems to control CdGAP residence at sites of cell-cell adhesion. CdGAP expression potently perturbs junctions and Ajuba binding inhibits CdGAP activity. Ajuba interacts with Rac1 and CdGAP via distinct domains and can potentially bring them in close proximity at junctions to facilitate activity regulation. Functionally, CdGAP-Ajuba interaction maintains junctional integrity in homeostasis and diseases: (i) gain-of-function CdGAP mutants found in Adams-Oliver Syndrome patients strongly destabilize cell-cell contacts and (ii) CdGAP mRNA levels are inversely correlated with E-cadherin protein expression in different cancers. We present conceptual insights on how Ajuba can integrate CdGAP binding and inactivation with the spatio-temporal regulation of Rac1 activity at junctions. Ajuba provides a novel mechanism due to its ability to bind to CdGAP and Rac1 via distinct domains and influence the activation status of both proteins. This functional interplay may contribute towards conserving the epithelial tissue architecture at steady-state and in different pathologies.

Defining functional interactions during biogenesis of epithelial junctions.

In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell-cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases.

Teriparatide and denosumab combination therapy and skeletal metabolism.

Several therapies are available for osteoporis. Understanding the bone turnover changes and their mutual realtionship gives an overall view and might lead to a target therapy INTRODUCTION: The aim of this study is to compare the changes in bone turnover markers in patients treated with either denosumab alone, teriparatide (TPTD) alone, or in a third therapeutic scheme, when TPTD was added to patients previously treated with denosumab. METHODS: Fifty-nine women over 65 years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3 months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), Sclerostin (SOST), and Dickkopf-related protein 1 (DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip. RESULTS: In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPTD was added 3 months later, both CTX and P1NP increased 3 months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment. CONCLUSIONS: In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.

Proline levels, oxidative metabolism and photosynthetic pigments during in vitro growth and acclimatization of Pitcairnia encholirioides L.B. Sm. (Bromeliaceae).

This study aimed to evaluate the variation in the levels of proline, oxidative metabolism and photosynthetic pigments in plants of Pitcairnia encholirioides grown in vitro under different conditions and after acclimatization. The analyses were performed after 150 days of in vitro cultivation in MS media supplemented with 10 µM GA3 or 0.2 µM NAA, sucrose at 15 or 30 g L-1, in test tubes which allowed gas exchange or in a hermetically sealed system, and 180 days after acclimatization. The in vitro maintenance in hermetically sealed flasks, with GA3 and 15 g L-1 sucrose had adverse metabolic effects, which was demonstrated by the lower proline and photosynthetic pigments accumulation and by the increase in antioxidant enzymes activities. After acclimatization, differences for proline and photosynthetic pigments were no longer found and the enzymatic activities ranged unevenly. The results suggest that the in vitro cultivation in media with 0.2 µM NAA and 30 g L-1 sucrose, in test tubes capped with closures which allowed gas exchange, is more suitable for micropropagation of P. encholirioides, providing a prolonged maintenance of in vitro cultures and plantlets with superior quality for ex vitro development.

Proline levels, oxidative metabolism and photosynthetic pigments during in vitro growth and acclimatization of Pitcairnia encholirioides L.B. Sm. (Bromeliaceae) / Niveis de prolina, do metabolismo oxidativo e dos pigmentos fotossintéticos durante o crescimento in vitro e aclimatização de Pitcairnia encholirioides L.B. Sm. (Bromeliaceae)

Abstract This study aimed to evaluate the variation in the levels of proline, oxidative metabolism and photosynthetic pigments in plants of Pitcairnia encholirioides grown in vitro under different conditions and after acclimatization. The analyses were performed after 150 days of in vitro cultivation in MS media supplemented with 10 µM GA3 or 0.2 µM NAA, sucrose at 15 or 30 g L–1, in test tubes which allowed gas exchange or in a hermetically sealed system, and 180 days after acclimatization. The in vitro maintenance in hermetically sealed flasks, with GA3 and 15 g L–1 sucrose had adverse metabolic effects, which was demonstrated by the lower proline and photosynthetic pigments accumulation and by the increase in antioxidant enzymes activities. After acclimatization, differences for proline and photosynthetic pigments were no longer found and the enzymatic activities ranged unevenly. The results suggest that the in vitro cultivation in media with 0.2 µM NAA and 30 g L–1 sucrose, in test tubes capped with closures which allowed gas exchange, is more suitable for micropropagation of P. encholirioides, providing a prolonged maintenance of in vitro cultures and plantlets with superior quality for ex vitro development.

Resumo Este trabalho objetivou avaliar a contribuição da prolina, do metabolismo oxidativo e dos pigmentos fotossintéticos na propagação in vitro e aclimatização de Pitcairnia encholirioides, uma bromélia criticamente ameaçada de extinção. As análises foram realizadas após 150 dias de cultivo in vitro em meio MS suplementado com 10 µM de GA3 ou 0,2 µM de ANA, 15 ou 30 g L–1 de sacarose, em tubos de ensaio que permitiam trocas gasosas ou em sistema hermeticamente vedado, e também 180 dias após aclimatização. A manutenção in vitro em frascos hermeticamente fechados, com GA3 e 15 g L–1 de sacarose apresentou efeito metabólico adverso, demonstrado pelo menor acúmulo de prolina e pigmentos fotossintéticos e também pelo aumento das atividades de enzimas antioxidantes. Após aclimatização, as diferenças para prolina e pigmentos fotossintéticos não foram mais encontradas e as atividades enzimáticas variaram de maneira desuniforme. Os resultados sugerem que o cultivo in vitro em meio com 0,2 µM de ANA e 30 g L–1 de sacarose, em tubos fechados com tampas que permitem trocas gasosas, é mais adequado para a micropropagação de P. encholirioides, proporcionando uma manutenção prolongada das culturas in vitro e plântulas com qualidade superior para o desenvolvimento ex vitro.

Integrity of the dorsolateral periaqueductal grey is essential for the fight-or-flight response, but not the respiratory component of a defense reaction.

Periaqueductal grey is believed to be one of the key structures of the central respiratory stress network. Previous studies established that stimulation of the periaqueductal grey, especially its dorsolateral division (dlPAG), evokes tachypnea as well as increases in other autonomic parameters and motor activity. We investigated the effects of blockade of the dlPAG with GABAA agonist muscimol on respiration during stress and presentation of brief alerting stimuli in conscious unrestrained rats. We found that integrity of the dlPAG is not essential for stress-induced increase in basal/resting respiratory rate or for generation of respiratory responses to brief alerting stimuli. However, blockade of the dlPAG reduced the amount of motor activity and concomitant high-frequency respiratory activity during restraint and the first 5min of novelty stress. We conclude that the integrity of the dlPAG is not essential for generation of respiratory component of the defense reaction, but it mediates expression of the fight-or-flight response including its respiratory component.

Large oesophageal epiphrenic diverticulum resected by transhiatal robotic-assisted approach -- case report.

INTRODUCTION: Epiphrenic diverticula (ED) represent about 20% of oesophageal diverticula. They are considered to be pulsion diverticula, characterized by out pouchings of the oesophageal mucosa originating in the distal 10 cm of the oesophagus and are frequently associated with spastic oesophageal dysmotility. The most frequent clinical manifestations of ED are dysphagia, regurgitations and chest pain. Only symptomatic diverticula should be treated by surgery. The surgical procedure can be performed minimally invasively by robotic approach and consists of diverticulectomy,hiatus calibration and an antireflux procedure, usually adding an esophagomiotomy as well. CASE-REPORT: We present the case of 43-year-old male patient who was admitted for a four-month history of epigastric pain, pyrosis and regurgitations. Preoperative investigation shave shown an epiphrenic diverticulum 6 cm large in diameter.A robotic-assisted transhiatal diverticulectomy with a linear endostapler, hiatal calibration and a Nissen-Rossetti fundoplication were performed using a three-arm da Vinci Robotic System. Operative time was 150 min. Postoperative course was uneventful and the patient was discharged on postoperative day 9, without complications. Ten days later,he came back and was readmitted under emergency status for right chest pain, dyspnoea and fetid breath, being diagnosed with a right empyema secondary to a delayed fistula of the oesophageal suture line. A right minimal pleurotomy and pleural drainage under local anaesthesia were performed and an intravenous antibiotherapy was started with complete remission of symptomatology, the patient remaining asymptomatic after 18 months of follow-up. CONCLUSIONS: Robotic approach is a feasible and safe minimally invasive surgical option in the treatment of selected cases of ED. We consider transhiatal abdominal robotic approach possible in almost all cases of ED, regardless of size,thus avoiding thoracic approach and its possible major complications.The most common serious complication after surgery of ED is post diverticulectomy suture line fistula, but if properly and rapidly diagnosed it could be conservatively treated with very good results.

Occult thyroid carcinoma in our experience -- should we reconsider total thyroidectomy for benign thyroid pathology?

BACKGROUND: The reported incidence rate of occult thyroid carcinoma in patients operated for benign thyroid pathology has been much higher than expected in the last years,especially for multinodular goitre, which raises the question about which should the proper surgical management for these cases be. AIM: To assess the incidence rate of OTC in a single medium volume surgical center and to establish the correct indication for initial surgical management, as well as to identify the benign thyroid pathology most frequently associated with OTC. We also reviewed the relevant scientific literature on this topic. MATERIAL AND METHOD: We conducted a retrospective study in the General Surgery Clinic of "Prof. dr. Agrippa Ionescu" Clinical Emergency Hospital, Bucharest, on a series of 145 patients who underwent surgical interventions for preoperatively diagnosed benign thyroid pathology over a ten year period, between 1st January 2002 - 31st December 2012. All cases of known thyroid cancer were excluded. RESULTS: Incidence rate of occult thyroid carcinoma in our series was 6.9 % (10 out of 145 patients), 80 % of them being diagnosed with multinodular goitre and two cases (20 %) with Hashimoto's lymphocytic thyroiditis. 6.8 % of all patients with multinodular goitre were found to present occult carcinoma,but this association was without statistical significance(p 0.05). Incidence rate of occult cancer among patients with Hashimoto thyroiditis was proved to be as high as 28.6%,statistically significant (p=0.020). The mean size of postoperatively diagnosed occult microcarcinoma was 7 mm, ranging between 3 mm and 14 mm, 90% of them being smaller than 1cm. Histologically, papillary microcarcinoma was found in all cases. The mean age of the patients diagnosed with occult microcarcinoma was 47.8 years with majority of the female gender. The most frequent operation performed was total thyroidectomy (70.8%). Overall morbidity in our series was 6.9% with a 0.7 % mortality rate (1 case). CONCLUSIONS: In our opinion, primary total thyroidectomy should be performed as the procedure of choice for the most part of preoperatively diagnosed benign thyroid pathology and particularly for multinodular goitre and Hashimoto thyroiditis,in order to radically resect all possible foci of aggressive thyroid microcarcinomas.Abbreviations and Acronyms: OTC (Occult Thyroid Carcinoma), PTMC (Papillary Thyroid Microcarcinoma); TT(Total Thyroidectomy), MNG (Multinodular Goitre), GD(Graves' disease), TNG (Toxic Nodular Goitre), FNAB(fine-needle aspiration biopsy).

Ethylene synthesis inhibition effects on oxidative stress and in vitro conservation of Lippia filifolia (Verbenaceae).

This study aimed to investigate the effects of ethylene biosynthesis inhibitors on oxidative metabolisms and the in vitro conservation of Lippia filifolia, using the lipid peroxidation index (TBARS), antioxidative enzymes and pigments as biomarkers. We found that EDTA, sodium thiosulfate (STS) and especially Co had protective effects on oxidative stress in tissues cultured in vitro, resulting in a delay of the senescence and the reduction of subcultures frequency, contributing to the germplasm conservation of this species.

Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men.

CONTEXT: Strontium ranelate reduces vertebral and nonvertebral fracture risk in postmenopausal osteoporosis. OBJECTIVE: The objective of this study was to determine the efficacy and safety of strontium ranelate in osteoporosis in men over 2 years (main analysis after 1 year). DESIGN: This was an international, unbalanced (2:1), double-blind, randomized placebo-controlled trial (MALEO [MALE Osteoporosis]). SETTING: This international study included 54 centers in 14 countries. PARTICIPANTS: PARTICIPANTS were 261 white men with primary osteoporosis. INTERVENTION: Strontium ranelate at 2 g/d (n = 174) or placebo (n = 87) was administered. MAIN OUTCOME MEASURES: Lumbar spine (L2-L4), femoral neck, and total hip bone mineral density (BMD), biochemical bone markers, and safety were measured. RESULTS: Baseline characteristics were similar in both groups in the whole population (age, 72.9 ± 6.0 years; lumbar spine BMD T-score, -2.7 ± 1.0; femoral neck BMD T-score, -2.3 ± 0.7). Men who received strontium ranelate over 2 years had greater increases in lumbar spine BMD than those who received placebo (relative change from baseline to end, 9.7% ± 7.5% vs 2.0% ± 5.5%; between-group difference estimate (SE), 7.7% (0.9%); 95% confidence interval, 5.9%-9.5%; P < .001). There were also significant between-group differences in relative changes in femoral neck BMD (P < .001) and total hip BMD (P < .001). At the end of treatment, mean levels of serum cross-linked telopeptides of type I collagen, a marker of bone resorption, were increased in both the strontium ranelate group (10.7% ± 58.0%; P = .022) and the placebo group (34.9% ± 65.8%; P < .001). The corresponding mean changes of bone alkaline phosphatase, a marker of bone formation, were 6.4% ± 28.5% (P = .005) and 1.9% ± 25.4% (P = .505), respectively. After 2 years, the blood strontium level (129 ± 66 µmol/L) was similar to that in trials of postmenopausal osteoporosis. Strontium ranelate was generally well tolerated. CONCLUSIONS: The effects of strontium ranelate on BMD in osteoporotic men were similar to those in postmenopausal osteoporotic women, supporting its use in the treatment of osteoporosis in men.

Scavenging of NADPH oxidase-derived superoxide anions improves depressed baroreflex sensitivity in spontaneously hypertensive rats.

In pathological conditions, such as hypertension, there is impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the depressed baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). Male 10-week-old SHR (n = 14) and their controls (Wistar-Kyoto (WKY) rats; n = 14) underwent femoral artery and vein catheterization for conscious blood pressure recording and drug administration. The BRS was obtained by the drug-induced method using phenylephrine (8 µg/kg, i.v.) and sodium nitroprusside (25 µg/kg, i.v.) before and after the administration of tiron (30 mg/kg, i.v.), a superoxide dismutase mimetic, or apocynin (30 µg/kg), an NADPH oxidase inhibitor. Spontaneously hypertensive rats was significantly hypertensive compared with WKY rats (160 ± 7 vs 105 ± 2 mmHg, respectively). However, there was no significant difference in heart rate between the two groups (388 ± 10 vs 370 ± 20 b.p.m.). In addition, SHR exhibited a diminished BRS compared with WKY rats (-1.34 ± 0.11 vs -2.91 ± 0.20 b.p.m./mmHg, respectively). Administration of tiron improved BRS in SHR (from -1.34 ± 0.11 to 2.26 ± 0.21 b.p.m./mmHg), as did apocynin (to -2.14 ± 0.23 b.p.m./mmHg). Serum samples from SHR (n = 20) and WKY rats (n = 20) were collected for thiobarbituric acid-reactive substances assays before and after tiron or apocynin to confirm the reduction in oxidative stress. There was considerably greater oxidative stress in SHR compared with WKY rats (36.2 ± 3.0 vs 13.3 ± 2.6 nmol/L, respectively). Both apocynin and tiron treatment reduced the oxidative stress in SHR (from 36.2 ± 3.0 to 21.5 ± 3.0 nmol/L and from 37.2 ± 3.9 to 21.9 ± 1.6 nmol/L, respectively). The data suggest that acute scavenging of NADPH oxidase-derived superoxide improves baroreflex sensitivity in SHR.

Clinical characteristics and incidence of first fracture in a consecutive sample of post-menopausal women attending osteoporosis centers: The PROTEO-1 study.

BACKGROUND: Osteoporosis is a highly prevalent disease and fractures are a major cause of disability and morbidity. AIM: The purpose of this study was to characterize post-menopausal women attending osteoporosis centers in Italy, to evaluate physician management, and to determine the incidence of first osteoporotic fracture. SUBJECTS AND METHODS: PROTEO-1 was an observational longitudinal study with a 12-month follow-up. Data were collected from women attending osteoporosis centers. Women without prevalent fracture were eligible to enter the 1-yr follow-up phase: the clinical approach to patients according to their fracture risk profile and the incidence of fracture were recorded. RESULTS: 4269 patients were enrolled in 80 centers in the cross-sectional phase; 34.2% had an osteoporotic fracture at baseline. Patients with prevalent fractures were older and more likely to be treated compared with non-fractured patients. The incidence of vertebral or hip fracture after 1 yr was 3.84%, regardless of the calculated risk factor profile, and was significantly higher in patients with back pain at baseline (4.2%) compared with those without back pain (2.2%; p=0.023). Generally, physicians prescribed more blood exams and drugs to patients at higher risk of fracture. Among fractured patients only 24% were properly treated; the rate of non-responders to treatment was about 4%. CONCLUSIONS: In a large, unselected sample of post-menopausal women attending osteoporosis centers, those without previous fracture were at substantial risk of future fracture, regardless of their theoretical low 10-yr fracture risk. The presence of back pain in women without previous fracture warrants close attention.