Real-time in vivo ROS monitoring with luminescent nanoparticles reveals skin inflammation dynamics.

Reactive oxygen species (ROS) are key regulators in numerous pathological contexts, including cancer or inflammation. Their role is complex, which justifies the need for methods enabling their quantitative and time-resolved monitoring in vivo, in the perspective to profile tissues of individual patients. However, current ROS detection methods do not provide these features. Here, we propose a new method based on the imaging of lanthanide-ion nanoparticles (GdVO4:Eu), whose photoluminescence is modulated by the surrounding ROS concentration. We monitored their luminescence after intradermic injection in a mouse ear submitted to an inflammation-inducing topical stimulus. Based on this approach, we quantified the ROS concentration after inflammation induction and identified a two-step kinetics of ROS production, which may be attributed to the response of resident immune cells and their further recruitment at the inflammation locus.

Luminescent lanthanide nanoparticle-based imaging enables ultra-sensitive, quantitative and multiplexed in vitro lateral flow immunoassays.

Lateral Flow Assays (LFAs) have been extensively used on-site to rapidly detect analytes, possibly in complex media. However, standard gold nanoparticle-based LFAs lack sensitivity and cannot provide quantitative measurements with high accuracy. To overcome these limitations, we image lanthanide-doped nanoparticles (YVO4:Eu 40%) as new luminescent LFA probes, using a homemade reader coupled to a smartphone and propose an original image analysis allowing strip quantification regardless of the shape of the test band signal. This method is demonstrated for the detection of staphylococcal enterotoxins SEA, SEG, SEH, and SEI. A systematic comparison to state-of-the-art gold nanoparticle-based LFA revealed an analytical sensitivity enhancement of at least one order of magnitude. We furthermore provided measurements of absolute toxin concentration over two orders of magnitude and demonstrated simultaneous quantitative detection of multiple toxins with unaltered sensitivity. In particular, we reached concentrations 100 times lower than the ones reported in the literature for on-site multiplexed LFA targeting enterotoxins. Altogether, these results highlight that our luminescent nanoparticle-based method provides a powerful and versatile on-site framework to detect multiple biomolecules with sensitivity approaching that obtained by ELISA. This paves the way to a change of paradigm in the field of analytical immunoassays by providing fast in situ quantitative high sensitivity detection of biomarkers or pathogens.

Obturator hernias: a systematic review of the literature.

PURPOSE: Obturator hernias (OH) are extremely rare hernias, accounting for 0.07-1% of all hernias. This is the first systematic review investigating their presentation, imaging, treatment outcomes, and recurrence rate. METHODS: After a detailed search in electronic search engines, 74 studies matched our criteria. A review of these reports was conducted and the full texts were examined. RESULTS: A total of 146 patients with a mean age of 78.8 years were included in our analysis, with 40.1%, 29.9%, and 25.2% of patients suffering from either a right, a left or bilateral OH, respectively. OH were associated with non-specific symptoms and signs; bowel obstruction being the most common. Howship-Romberg sign was present in 56.2% of patients. Computed tomography (CT) scan was the most frequently used diagnostic modality, inversely associated with perioperative mortality. Mesh repair demonstrated a significantly improved perioperative morbidity rate, compared with non-mesh repair. Approximately 30% of patients underwent a laparoscopic operation, which was associated with significantly decreased morbidity and mortality rate as well as length of hospital stay, compared with the open repair. CONCLUSION: OHs are not associated with specific symptoms and signs; thus, they constitute a diagnostic challenge, requiring a high level of clinical suspicion. Undoubtedly, CT scan of the abdomen is the gold standard diagnostic tool. Their operative repair is mandatory, with the laparoscopic approach demonstrating significant advantages over the open repair.

Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein after Roux-en-Y gastric bypass or sleeve gastrectomy: a 1-year prospective observational study.

PURPOSE: Low-grade inflammation in obesity contributes to the development of cardiovascular disease, diabetes mellitus and cancer, and is associated with increased mortality. The purpose of this 1-year prospective observational study was to examine the weight loss effect of bariatric surgery on plasma concentrations of two inflammatory markers, namely high-sensitivity C-reactive protein (hsCRP) and soluble urokinase-type plasminogen activator receptor (suPAR), in patients with obesity. METHODS: Sixteen subjects without obesity and 32 patients with obesity class III, who had already settled upon Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were included in the study. Subjects without obesity were examined once, at baseline; patients with obesity were examined preoperatively (baseline) and 3, 6 and 12 months postoperatively. RESULTS: Plasma suPAR and hsCRP concentrations at baseline were higher in patients with obesity than in lean participants (2.68 ± 0.86 vs 1.86 ± 0.34 ng/mL, p < 0.001 and 9.83 ± 9.55 vs 1.36 ± 1.95 mg/dL, p < 0.001). Levels of suPAR following bariatric surgery increased significantly 3 months after either RYGB or SG (3.58 ± 1.58 vs 3.26 ± 0.7 ng/mL, respectively) and declined at 6 (3.19 ± 1.75 vs 2.8 ± 0.84 ng/mL, respectively) and 12 months (2.6 ± 1.5 vs 2.22 ± 0.49 ng/mL, respectively; p < 0.05 for the effect of time on suPAR levels during the study), whereas those of hsCRP declined consistently after bariatric surgery (3 months: 5.44 ± 3.99 vs 9.47 ± 11.98 mg/dL, respectively; 6 months; 5.39 ± 5.6 vs 10.25 ± 17.22 mg/dL, respectively; and 12 months: 2.23 ± 2.5 vs 3.07 ± 3.63 mg/dL, respectively; p < 0.001 for the effect of time on hsCRP levels during the study). 1-year change in BMI was negatively associated with suPAR levels at 12 months. CONCLUSION: Our findings support an association between obesity and low-grade inflammation. Weight loss following bariatric surgery is associated with a consistent decline in plasma hsCRP, while plasma suPAR levels increase at 3 months and decline by 12 months.

A Genetic Risk Score for the Estimation of Weight Loss After Bariatric Surgery.

BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most frequent bariatric surgery procedures worldwide. In this prospective study, we examined the association of a genetic risk score (GRS) with loss of excess weight after bariatric surgery. METHODS: A total of forty-seven morbidly obese Greek patients who underwent SG (81%) or RYGB were recruited, followed up for 2 years and genotyped. Weight loss after surgery was reported as the percentage of excess weight that was lost (%EWL) at 12 and 24 months after surgery. A GRS was constructed based on previously BMI- and WHR-related single nucleotide polymorphisms (SNPs) that were found significantly correlated with weight loss after bariatric surgery in our population. The level of post-surgery %EWL after 12 and 24 months was estimated through two multiple linear regression models that considered the effects of relevant genetic risk variants. RESULTS: The first proposed model suggested that the predictor variables of GRS, age, and BMI had a significant effect on %EWL12m. GRS was significantly associated with %EWL12m, indicating a 4.618% decrease of %EWL12m per score unit. The second model indicated a positive correlation between %EWL24m and %EWL12m, suggesting that while post-surgery weight loss increased during the first 12 months, an increase was expected in the next 12 months as well. GRS was also significantly associated with %EWL24m, indicating approximately 3% decrease of %EWL24m per score unit. CONCLUSION: GRS can be used in the future together with other preoperative parameters in order to predict the outcome of bariatric surgery.

Comparison Between Minimally Invasive and Open Gastrectomy for Gastric Cancer in Europe: A Systematic Review and Meta-analysis.

AIMS: We compared laparoscopic and robotic gastrectomies with open gastrectomies and with each other that were held for gastric cancer in Europe. METHODS: We searched for studies conducted in Europe and published up to 20 February 2015 in the PubMed database that compared laparoscopic or robotic with open gastrectomies for gastric cancer and with each other. RESULTS: We found 18 original studies (laparoscopic vs open: 13; robotic vs open: 3; laparoscopic vs robotic: 2). Of these, 17 were non-randomized trials and only 1 was a randomized controlled trial. Only four studies had more than 50 patients in each arm. No significant differences were detected between minimally invasive and open approaches regarding the number of retrieved lymph nodes, anastomotic leakage, duodenal stump leakage, anastomotic stenosis, postoperative bleeding, reoperation rates, and intraoperative/postoperative mortality. Nevertheless, laparoscopic procedures provided higher overall morbidity rates when compared with open ones, but robotic approaches did not differ from open ones. On the contrary, blood loss was less and hospital stay was shorter in minimally invasive than in open approaches. However, the results were controversial concerning the duration of operations when comparing minimally invasive with open gastrectomies. Additionally, laparoscopic and robotic procedures provided equivalent results regarding resection margins, duodenal stump leakage, postoperative bleeding, intraoperative/postoperative mortality, and length of hospital stay. On the contrary, robotic operations had less blood loss, but lasted longer than laparoscopic ones. Finally, there were relatively low conversion rates in laparoscopic (0%-6.7%) and robotic gastrectomies (0%-5.6%) in most studies. CONCLUSION: Laparoscopic and robotic gastrectomies may be considered alternative approaches to open gastrectomies for treating gastric cancer. Minimally invasive operations are characterized by less blood loss and shorter hospital stay than open ones. In addition, robotic procedures have less blood loss, but last longer than laparoscopic ones.

Fast quantitative ROS detection based on dual-color single rare-earth nanoparticle imaging reveals signaling pathway kinetics in living cells.

Reactive oxygen species (ROS), and notably hydrogen peroxide H2O2, are cellular second messengers that are known to control a variety of signaling processes. They can finely regulate the dynamics of signal transduction, cell response and ultimately tissue function. However, there are very few local, quantitative and time-resolved descriptions of their cellular organization at the scale of molecular reactions, due to the lack of efficient sensors. We thus developed a novel nanoprobe-based ROS detection system using the simultaneous imaging of single lanthanide nanoparticles (YAG:Ce and chemically reduced Gd0.6Eu0.4VO4). We reveal that both particle luminescence signals are controlled by their H2O2 local environment. By simultaneously tracking their luminescence, we devised a new approach providing a quantitative (0.5 µM accuracy in the 1-10 µM range) H2O2 measurement with a 500 ms time resolution, surpassing all existing methods by two orders of magnitude, and revealing previously inaccessible molecular events controlling ROS concentration. We used this nanoprobe in living cells to track fast signaling pathways, by measuring the dynamics of H2O2 intracellular concentrations, induced by endothelin-1 (ET-1) stimulation. We thus revealed the mechanisms controlling ROS production, notably the activity modulation of the ROS-producing enzyme NADPH oxidase by fast (<10 s) EGFR transactivation, and measured quantitatively their kinetic parameters through a minimal analytical model. Altogether, these results illustrate how lanthanide nanoparticle-based sensors are a powerful tool to dynamically probe molecular mechanisms shaping the oxidative cell response.

The intensity of menopausal symptoms is associated with episodic memory in postmenopausal women.

OBJECTIVE: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women. METHODS: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene's Climacteric scale. RESULTS: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = -0.568, p = 0.009 and b-coefficient = -0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = -0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = -0.558, p = 0.001 and b-coefficient = -0.474, p = 0.005) and HVLT discrimination index (b-coefficient = -0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = -0.457, p = 0.006) and HVLT total (b-coefficient = -0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = -0.593, p < 0.001), BVMT delayed recall (b-coefficient = -0.492, p = 0.002). CONCLUSION: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.

Circulating androgens are associated with mood disturbances in young postmenopausal women.

OBJECTIVES: We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. METHODS: Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. RESULTS: The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. CONCLUSION: Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

Alpha-thalassemia intellectual disability: variable phenotypic expression among males with a recurrent nonsense mutation - c.109C>T (p.R37X).

Alpha-thalassemia intellectual disability, one of the recognizable X-linked disability syndromes, is characterized by short stature, microcephaly, distinctive facies, hypotonic appearance, cardiac and genital anomalies, and marked skewing of X-inactivation in female carriers. With the advent of next generation sequencing, mutations have been identified that result in less severe phenotypes lacking one or more of these phenotypic manifestations. Here we report five unrelated kindreds in which a c.109C>T (p.R37X) mutation segregates with a variable but overall milder phenotype. The distinctive facial appearance of alpha-thalassemia intellectual disability was present in only one of the 18 affected males evaluated beyond the age of puberty, although suggestive facial appearance was present in several during infancy or early childhood. Although the responsible genetic alteration is a nonsense mutation in exon 2 of ATRX, the phenotype appears to be partially rescued by the production of alternative transcripts and/or other molecular mechanisms.

The human ether-a'-go-go related gene (hERG) K+ channel blockade by the investigative selective-serotonin reuptake inhibitor CONA-437: limited dependence on S6 aromatic residues.

Diverse non-cardiac drugs adversely influence cardiac electrophysiology by inhibiting repolarising K(+) currents mediated by channels encoded by the human ether-a-go-go-related gene (hERG). In this study, pharmacological blockade of hERG K(+) channel current (I(hERG)) by a novel investigative serotonin-selective reuptake inhibitor (SSRI), CONA-437, was investigated. Whole-cell patch-clamp measurements of I(hERG) were made from human embryonic kidney (HEK 293) cells expressing wild-type (WT) or mutant forms of the hERG channel. With a step-ramp voltage-command, peak I(hERG) was inhibited with an IC(50) of 1.34 µM at 35 ±1°C; the IC(50) with the same protocol was not significantly different at room temperature. Voltage-command waveform selection had only a modest effect on the potency of I(hERG) block: the IC50 with a ventricular action potential command was 0.72 µM. I(hERG) blockade developed rapidly with time following membrane depolarisation and showed a weak dependence on voltage, accompanied by a shift of ≈ -5 mV in voltage-dependence of activation. There was no significant effect of CONA-437 on voltage-dependence of I(hERG) inactivation, though at some voltages an apparent acceleration of the time-course of inactivation was observed. Significantly, mutation of the S6 aromatic amino acid residues Y652 and F656 had only a modest effect on I(hERG) blockade by CONA-437 (a 3-4 fold shift in affinity). CONA-437 at up to 30 µM had no significant effect on either Nav1.5 sodium channels or L-type calcium channels. In conclusion, the novel SSRI CONA-437 is particularly notable as a gating-dependent hERG channel inhibitor for which neither S6 aromatic amino-acid constituent of the canonical drug binding site on the hERG channel appears obligatory for I(hERG) inhibition to occur.

The incidence of HPV infection in anal cancer patients in Greece.

BACKGROUND AND AIM OF THE STUDY: Although anal cancer represents a relatively uncommon malignancy, its incidence over the last five decades, has been reported as increased for both sexes, worldwide. Human papillomavirus (HPV) infection has been shown to be a major cause for its development. The aim of the present study is to report on clinical, epidemiological and virological data of squamous anal cancer in Greek patients. PATIENTS AND METHOD: Between January 2002 and December 2010, 11 Greek patients (6 females) who were diagnosed as suffering from squamous cell anal or perianal cancer, were treated in our Hospital. Formalin fixed paraffin embedded tissue samples, obtained at the time of the anal biopsy or surgery, were analyzed by PCR in order to identify the presence as well as the type of HPV infection. RESULTS: Overall, the presence of HPV DNA was detected in 6 out of the 11 patients (54.5%). The "high risk" HPV DNA was detected in 3 of them (2 women and 1 man), while the "low risk" HPV DNA was detected in the remaining three (2 women and 1 man). CONCLUSION: The incidence of HPV infection in squamous cell anal cancer Greek patients, is lower than other Western countries, probably reflecting differences in sexual habits in the Greek population.

A prenatally ascertained, maternally inherited 14.8 Mb duplication of chromosomal bands Xq13.2-q21.31 associated with multiple congenital abnormalities in a male fetus.

Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq13.2 to q21.31 in a male fetus with increased nuchal translucency in the first trimester and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed additional chromosomal material in the long arm of chromosome X at position Xq13. Analysis with high resolution array CGH revealed the additional material is in fact a duplication of the region Xq13.2-q21.13. The duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM. Analysis of the parents revealed the mother to be a carrier of the same duplication. After elected termination of the pregnancy at 28 weeks a detailed autopsy of the fetus allowed for genotype-phenotype correlations.

Efficacy and safety of DT56a compared to hormone therapy in Greek post-menopausal women.

BACKGROUND: Hormone therapy (HT) is the treatment of choice for the alleviation of menopausal symptoms; concerns, however, about its concomitant long-term health risks have limited its use. DT56a is a unique enzymatic isolate of soybeans. The purpose of our study was to evaluate the efficacy and safety of DT56a, compared to HT, in symptomatic post-menopausal women. SUBJECTS AND METHODS: Eighty-nine post-menopausal women were studied prospectively. Women with climacteric symptoms were randomly assigned to receive eitherDT56a (no.=27) or oral low dose continuous combined HT (no.=26). Symptomatic women not wishing to receive any treatment served as controls (no.=36). Menopausal symptoms as assessed through the Kupperman index, serum lipids and lipoproteins, calcium, as well as bone mineral density (BMD), endometrial thickness, and mammography were assessed at baseline and at 12 months. RESULTS: Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms (mean difference in Kupperman score, DT56a group: -3.98, HT group -5.601, no treatment group +1.76, p-value <0.001). Lumbar spine BMD T-score was significantly lower in women receiving no treatment, as opposed to the two treatment arms which showed no significant change (No treatment, baseline: -0.60, final: -0.85, p=0.001; HT, baseline: -84, final -0.99, p=0.79; DT56a, baseline -0.51, final: -0.76, p=0.75). No differences in femoral bone density, ET or mammography classification were detected in any of the treatment arms. Likewise, serum lipids or lipoproteins did not differ between the three groups. CONCLUSIONS: DT56a decreased menopausal symptoms significantly and in the same degree as HT.

MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women.

OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

Effect of tibolone and raloxifene on serum markers of apoptosis in postmenopausal women.

OBJECTIVES: To investigate the effect of tibolone and raloxifene on the serum apoptotic markers soluble Fas (sFas), soluble Fas ligand (sFasL) and cytochrome-c (cyt-c) in postmenopausal women. METHODS: A total of 89 healthy postmenopausal women, attending the University Menopause Clinic, were randomly allocated to tibolone (n =30), raloxifene (n =29) or no treatment (n =30). Serum apoptotic markers sFas, sFasL and cyt-c were measured at baseline and at 6 months. RESULTS: Serum sFasL decreased significantly in women receiving tibolone (baseline: 53.8±28.3 pg/ml, 6 months: 40.45±19.2 pg/ml, p =0.001), whilst sFas levels did not significantly change in this group. Serum sFas or sFasL did not change either in the raloxifene group or in the control group. Serum cyt-c concentrations were under the detection limit of the assay in all women assessed. CONCLUSIONS: Tibolone use resulted in a significant decrease in serum sFasL, but not in serum sFas. Raloxifene had no effect on either sFas or sFasL. These results may indicate that tibolone use is associated with a decrease in receptor-mediated apoptosis.

What is the actual fate of super-morbid-obese patients who undergo laparoscopic sleeve gastrectomy as the first step of a two-stage weight-reduction operative strategy?

The overall success-rate of the two-stage treatment plan for the treatment of super-morbid obesity has not yet been assessed. We reviewed the long-term results of 41 treated super-morbid-obese patients. Mean initial BMI was 59.5 ± 3.5 kg/m(2). Twelve patients (29.3 %) achieved after only LSG a BMI <35 kg/m(2) (mean 31.9 ± 2). They have lost 78.7 ± 11.8 % of excess body weight (EBW). The remaining 28 patients lost 48.1 ± 11.9 % of EBW and achieved a mean BMI of 44.2 ± 4.3 kg/m(2), thus requiring the second stage. Ten of them (24.4 % of the total or 35.7 % of those in need), were submitted to laparoscopic Roux-en-Y gastric bypass (LRYGBP). They lost 71.9 ± 4.3 % of EBW and have a mean BMI of 33.6 ± 2.7 kg/m(2). The 18 remaining patients have a BMI of 42 ± 3.6 kg/m(2) and they still suffer from morbid obesity. They have lost 48.5 ± 8.7 % of EBW. The mean rate of EBW loss for all the available 39 patients after either LSG or both LSG and LRYGBP has been 63.2 ± 16.5 % after a mean follow-up of 42.8 ± 19.5 months. Out of 41 patients, 1 died, 1 was lost to follow-up, 21 (51.2 %) achieved "healthy" BMIs and 18 (44 %) still require LRYGBP. The rate of cure of morbid obesity was 51.2 %. A remaining 44 % of super-morbid obese patients still need the completion LRYGBP but have not undergone it. Half of these patients have lost >50 % of their EBW. The two-stage strategy is an effective treatment plan for super-morbid obesity. A less patient-dependent strategy may be needed for a subset of patients.

Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress.

INTRODUCTION: Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. MATERIALS AND METHODS: The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder. CONCLUSIONS: In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women.

OBJECTIVES: To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. METHODS: One hundred and ten postmenopausal women aged 45-55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima-media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. RESULTS: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.