Insomnia and menopause: a narrative review on mechanisms and treatments.

The menopausal transition is associated with an increased frequency of sleep disturbances. Insomnia represents one of the most reported symptoms by menopausal women. According to its pathogenetic model (3-P Model), different predisposing factors (i.e. a persistent condition of past insomnia and aging per se) increase the risk of insomnia during menopause. Moreover, multiple precipitating and perpetuating factors should favor its occurrence across menopause, including hormonal changes, menopausal transition stage symptoms (i.e. hot flashes, night sweats), mood disorders, poor health and pain, other sleep disorders and circadian modifications. Thus, insomnia management implies a careful evaluation of the psychological and somatic symptoms of the individual menopausal woman by a multidisciplinary team. Therapeutic strategies encompass different drugs but also behavioral interventions. Indeed, cognitive behavioral therapy represents the first-line treatment of insomnia in the general population, regardless of the presence of mood disorders and/or vasomotor symptoms (VMS). Different antidepressants seem to improve sleep disturbances. However, when VMS are present, menopausal hormone therapy should be considered in the treatment of related insomnia taking into account the risk-benefit profile. Finally, given its good tolerability, safety, and efficacy on multiple sleep and daytime parameters, prolonged-released melatonin should represent a first-line drug in women aged ≥ 55 years.

Neurofibromatosis: caso clínico presentación poco habitual. oportunidad diagnostica familiar

Resumen La Neurofibromatosis (NF) es una genodermatosis autosómica dominante. La literatura reconoce varios síndromes clínicos diferentes dentro de los cuáles se describen tres formas principales: Neurofibromatosis tipo 1, Neurofibromatosis tipo 2 y Schwanomatosis. La más común de las tres es la NF1. Con una incidencia de 1 en 3000 y una penetrancia del 100% presenta amplio espectro de manifestaciones clínicas. Nosotros presentamos un caso de sexo femenino que consulta inicialmente por dolor relacionado a una lesión compatible con neuro fibroma con componente epidérmico y subcutáneo. Sin diagnóstico previo de la enfermedad a los 33 años, logramos la correspondiente captación de todos los integrantes de su familia quienes tampoco tenían diagnóstico.

Summary Neurofibromatosis is an autosomal dominant genodermatosis. The literature recognizes several different clinical syndromes within which three main forms are described: Neurofibromatosis type 1, Neurofibromatosis type 2 and Schwanomatosis. The most common of the three is NF1. With an incidence of 1 in 3000 and a penetrance of 100%, it presents a broad spectrum of clinical manifestations. We present a female case that initially consulted for pain related to a lesion compatible with neurofibroma with an epidermal and subcutaneous component. Without previous diagnosis of the disease at 33 years, we were able to diagnose all the members of his family, who also had no diagnosis.

The evolution of multigene panel testing for hereditary cancers.

A thorough family history evaluation remains a critical tool that helps identify those patients who are at risk for hereditary cancer. The American College of Obstetricians and Gynecologists (ACOG) recommends that all women receive a family history evaluation to screen for inherited risk, and that this information be regularly updated. Patients with an abnormal cancer family history need additional follow-up that may include hereditary cancer testing. Multigene panel testing provides comprehensive profiling for hereditary cancer patients by identifying more health risks than single genome testing. If hereditary cancer is established, patients should be counseled about management options, including increased surveillance, chemoprevention, and/or surgery. Establishing workflow protocols may help clinicians integrate hereditary cancer risk assessment into their practice.

18F-FDG uptake and calcifications on positron emission tomography/computed tomography in octogenarians with severe aortic stenosis.

AIM: The degree of inflammation within the atherosclerotic plaque can be detected non-invasively by positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG). The incidence of aortic plaques with 18F-FDG increased uptake in octogenarians with aortic stenosis is unknown. Aim of this study was to evaluate the frequency of inflamed aortic atherosclerotic plaques in octogenarians with or without severe aortic stenosis and their correlations with calcifications. METHODS: The study group comprised 27 patients older than 80 years who underwent a 18FDG PET/CT. Nine patients with severe symptomatic aortic stenosis, eligible to TAVI procedure (TAVI Group), and 18 patients age and sex matched, without clinical evidence of aortic stenosis (No TAVI Group), were selected and analysed. RESULTS: In the whole population 4/27 patients (9.3%) had a significant focal aortic vessel wall 18F-FDG increased uptake: 1 patient (11.1%) in TAVI group and 3 in non-TAVI Group (16.7%). Overall 81 aortic segments were analysed. 18F-FDG uptake rates were similar in the two groups (1/27, 3.7% in TAVI Group and 3/54, 5.5% in No TAVI Group, P=0.7). At CT scan calcifications were significantly more frequent in the TAVI Group compared to non-TAVI Group (23/27, 85.2% and 28/54, 51.8% P=0.005). None of the sites of arterial calcification had an increased focal 18F-FDG uptake. CONCLUSION: Irrespectively to the presence of aortic stenosis, a significant FDG plaque uptake in octogenarians is rare while calcifications are extremely frequent.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

Long term clinical outcomes in DES implantation for unprotected left main disease.

AIM: Generate a long term follow-up and evaluate the impact of clinical and procedural characteristics on long term events in percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation for unprotected left main coronary artery (ULMCA) disease. METHODS: Ninety-seven consecutive patients who underwent PCI with DES, either sirolimus (SES) or paclitaxel-eluting stent (PES), for de novo lesions in ULMCA were analyzed. No patients were excluded. Mean follow-up was 3 years (range 1-6.7 years). RESULTS: Technical and procedural success rate were 100% and 95.9%. According to the Academic Research Consortium definitions, cardiac death occurred in 6.1% of patients, reinfarction, target vessel revascularization (TVR) and target lesion revascularization (TLR) occurred in 6.1%, 17.5% and 4.2% of patients respectively. Definite stent thrombosis (ST) incidence was 1%, whereas possible ST occurred in 4.2% of patients. Postdilation was performed in 49.5% of patients and was, among all clinical and procedural characteristics, the only factor at multivariate analysis significantly related to lower MACE (25% vs. 46.9%, P=0.024, CI: 0.202 to 0.889) and TVR (8.3% vs. 26.5%, P=0.03 CI: 0.096-0.895). CONCLUSION: Long term follow-up in PCI of ULMCA disease shows favorable clinical results. Stent postdilation seems to have a protective role in DES PCI for ULMCA disease.

Effects of EPC capture stent and CD34+ mobilization in acute myocardial infarction.

AIM: Percutaneous coronary intervention (PCI) is the gold standard for the treatment of acute myocardial infarction (AMI), with the main limitation of in-stent restenosis for BMS and late stent thrombosis (ST) for both BMS and DES. Endothelial progenitor cells (EPC) CD34+ capture stents, promoting vascular healing, may be advantageous in preventing ST. Aim of the study is to evaluate the outcomes of AMI patients treated with EPC CD34+ capture stent and describe the mobilization kinetics of CD34+ and their clinical correlation. METHODS: Fifty AMI patients underwent primary PCI with EPC CD34+ capture stent. Serial assays of CD34+ were performed by flow-cytometric analysis. RESULTS: Procedural success rate was 100%. At six-months follow-up cardiac death, myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR) occurred respectively in 2%, 4%, 10% and 12% of patients. No case of ST was observed. The MACE-free survival was 81,2%. The mean peak value of plasmatic CD34+ was 4.69±3.76 cells/µL. A positive correlation was found between CD34+ concentration, age and infarct area. No correlation was detected between CD34+ concentration and occurrence of TVR, TLR and MACE. CONCLUSION: EPC capture stent implantation seems to be safe and effective in the clinical setting of AMI, representing a possible alternative to BMS and DES. CD34+ cells plasmatic concentration seems not to correlate to coronary restenosis and atheromasic disease progression.

Rationale and results of percutaneous coronary revascularization with endothelial progenitor cell capture stent in high-risk patients requiring undeferrable non-cardiac surgery.

AIM: Drug eluting stents (DES) are currently the gold standard for the treatment of significant coronary artery stenosis in high risk patients. In case of undeferrable non-cardiac surgery their use is still a challenge, due to the need of a prolonged dual antiplatelet therapy. We aimed to prospectively evaluate the efficacy and safety of the implantation of endothelial progenitor cells (EPC) capture stent followed by a short dual anti-platelet therapy (DAT) period in a high risk population of patients undergoing undeferrable non-cardiac surgery. METHODS: We examined all consecutive patients who received EPCs capture stents and underwent non-cardiac surgery within 60 days of percutaneous coronary intervention. Our primary outcome was the occurrences of cardiac death, myocardial infarction (MI), stent thrombosis (ST), target vessel revascularization (TVR) and major adverse cardiac events (MACE). RESULTS: Twenty-six patients underwent PCI and were enrolled, but only 20 underwent surgical intervention. Technical and procedural success rates were both 100%. No perioperative MACE was detected. After a mean long term follow-up of 15.4±10.3 months, 2 cases of cardiac death (10%), were recorded. No case of stent thrombosis was reported; no case of ischemia driven TLR was detected. The total MACE-free survival probability was 66.5%. CONCLUSION: EPC capture stent implantation in high-risk patients requiring undeferrable non-cardiac surgery seems to allow early cand safe discontinuation of DAT, and may be an attractive alternative to conventional stents.

Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT).

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Evaluation of the topical hemostatic efficacy and safety of TISSEEL VH S/D fibrin sealant compared with currently licensed TISSEEL VH in patients undergoing cardiac surgery: a phase 3, randomized, double-blind clinical study.

AIM: TISSEEL VH is the only commercially available fibrin sealant indicated as an adjunct to conventional methods of hemostasis during cardiac surgery. A next generation fibrin sealant (TISSEEL VH S/D) has been developed in frozen, ready-to-use form with an added virus inactivation step (solvent/detergent [S/D] treatment) to provide added safety and convenience to the currently licensed product. This study was performed to compare efficacy and safety of the two products. METHODS: Phase 3, prospective, randomized, double-blind, multicenter study to compare TISSEEL VH S/D to TISSEEL VH during cardiac surgery. The primary efficacy endpoint was the proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure. RESULTS: The proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure was 88.2% for TISSEEL VH S/D and 89.6% for TISSEEL VH in the intent-to-treat population. The difference in proportions, TISSEEL VH S/D minus TISSEEL VH, was 1.4% with a standard error of 3.70%. The lower 97.5% confidence bound of this difference was 8.6%, which is above the predefined noninferiority margin of 15%. Therefore, TISSEEL VH S/D is at least as efficacious as TISSEEL VH. The safety profile of TISSEEL VH S/D was very similar to that of currently licensed TISSEEL VH as assessed by the safety endpoints. CONCLUSION: TISSEEL VH S/D is safe and effective for use as an adjunct to hemostasis in patients undergoing cardiac surgery.

A participação de psicólogos na avaliação de políticas públicas para mulheres / The participation of psychologists in the evaluation of public politics for women

No presente artigo, pretendemos discutir a participação de psicólogos na avaliação de políticas públicas voltadas para mulheres em situação de violência de gênero. A análise que apresentaremos refere-se a dois encontros de mulheres que ocorreram na cidade de Belo Horizonte/MG e tiveram como objetivo avaliar os serviços prestados pelos programas e seus impactos na vida das mulheres atendidas. O processo de avaliação foi realizado com base no método de ficinas em dinâmica de grupo, que trabalha com os sujeitos de modo integral, as maneiras como eles pensam, sentem e agem. Participaram dos grupos mulheres que já foram atendidas pelo Benvinda - Centro de Apoio a Mulher e abrigadas na Casa Abrigo Sempre Viva (CASV). Neste processo procuramos estimular a emergência de sujeitos sociais ativos que buscam a transformação social da realidade na qual vivem. Foram avaliados os programas de atendimento a mulheres em situação de violência de gênero no município, a saber, o Benvinda, a CASV e a delegacia especializada em crimes contra a mulher. Os dados indicaram qualidades dos programas, críticas a eles e sugestões para possíveis melhorias nos serviços prestados. Outro aspecto trabalhado nos grupos foram as mudanças ocorridas nas vidas das mulheres após passarem pelos programas, sendo que a maioria das mulheres que participaram dos grupos afirmou que conseguiu reestruturar sua vida sem os agressores (AU)

A participação de psicólogos na avaliação de políticas públicas para mulheres / The participation of psychologists in the evaluation of public politics for women

No presente artigo, pretendemos discutir a participação de psicólogos na avaliação de políticas públicas voltadas para mulheres em situação de violência de gênero. A análise que apresentaremos refere-se a dois encontros de mulheres que ocorreram na cidade de Belo Horizonte/MG e tiveram como objetivo avaliar os serviços prestados pelos programas e seus impactos na vida das mulheres atendidas. O processo de avaliação foi realizado com base no método de ficinas em dinâmica de grupo, que trabalha com os sujeitos de modo integral, as maneiras como eles pensam, sentem e agem. Participaram dos grupos mulheres que já foram atendidas pelo Benvinda - Centro de Apoio a Mulher e abrigadas na Casa Abrigo Sempre Viva (CASV). Neste processo procuramos estimular a emergência de sujeitos sociais ativos que buscam a transformação social da realidade na qual vivem. Foram avaliados os programas de atendimento a mulheres em situação de violência de gênero no município, a saber, o Benvinda, a CASV e a delegacia especializada em crimes contra a mulher. Os dados indicaram qualidades dos programas, críticas a eles e sugestões para possíveis melhorias nos serviços prestados. Outro aspecto trabalhado nos grupos foram as mudanças ocorridas nas vidas das mulheres após passarem pelos programas, sendo que a maioria das mulheres que participaram dos grupos afirmou que conseguiu reestruturar sua vida sem os agressores.

Polyethylene glycol but not mifepristone prevents intestinal lymphocyte loss following treadmill exercise in mice.

UNLABELLED: Circulating lymphocyte numbers decrease following intense physical activity, possibly due to exercise-induced apoptosis. Increased reactive oxygen species (ROS) and glucocorticoids (GC) following exercise contribute to lymphocyte apoptosis. Intestinal lymphocyte (IL) numbers also decrease following exercise. AIM: The purpose of this study was to determine the contribution of GC to exercise-induced IL loss. METHODS: Female C57BL/6 mice (n = 178) were randomized to five drug conditions: (1) single injection of the glucocorticoid receptor antagonist mifepristone (MIF) solubilized in polyethylene glycol (PEG); (2) three injections of MIF (repeated MIF) PEG; (3) single injection of PEG (PEG); (4) three injections of PEG (repeated PEG); or (5) repeated injections of saline (SAL). Within each drug group mice were further randomized to exercise conditions: (1) control condition (non-exercised); (2) treadmill running with sacrifice immediately following the exercise; or (3) treadmill running with sacrifice 24 h after completion of the exercise. RESULTS: There was a significant exercise effect, across all T lymphocyte subsets, in SAL (P < 0.01), PEG (P < 0.01) and MIF (P < 0.01) treated mice but not in mice given repeated PEG or repeated MIF exposure. The exercise effect was due to reduced IL numbers 24 h post-exercise compared with non-exercised controls. CONCLUSION: These results suggest that GC are not directly responsible for IL cell loss following exercise. Repeated exposure to PEG may confer protection in the gastrointestinal tract from exercise-induced lymphocyte depletion. Because PEG inhibits ROS generation in experimental cell injury, the mechanisms for IL loss after exercise may involve oxidative stress.

Intravenous catecholamine administration affects mouse intestinal lymphocyte number and apoptosis.

The purposes of this study were to determine plasma and intestinal epinephrine (E) and norepinephrine (NE) concentrations in mice after exercise stress and, the effect of intravenous injection of E and NE (at concentrations during exercise) on viability of intestinal lymphocytes (IL). Exhaustive exercise significantly elevated plasma E and NE, and intestinal E, compared with sedentary animals. Twenty-four hours after intravenous NE administration, IL counts were higher (p<0.001) and % apoptotic IL were lower (p<0.001) than saline conditions. E resulted in fewer apoptotic IL at 24 h compared to saline controls. E and NE differentially influence IL numbers at 24 h after injection although both result in fewer % apoptotic IL relative to mice given saline only.

Beta-adrenergic receptor blockade during exercise decreases intestinal lymphocyte apoptosis but not cell loss in mice.

Catecholamines induce apoptosis in various lymphoid populations. This process can occur with both alpha- and beta-adrenoreceptors. Heavy exercise increases plasma catecholamine concentrations, and is also a cause of lymphocyte apoptosis, a possible explanation for postexercise lymphocytopenia. The purpose of this study was to examine the effects of adrenoreceptor antagonism on exercise-induced decreases and apoptosis of intestinal lymphocytes. Mice received an intraperitoneal injection of phentolamine (a nonselective alpha-blocker), nadolol (a nonselective beta-blocker), or saline (vehicle) prior to an exhaustive bout of exercise. Total intestinal lymphocyte numbers, percent and number of CD3+ lymphocytes, and cell viability were assessed. Neither alpha- nor beta-antagonism prevented exercise-induced cell loss in the intestine; however, pretreatment with nadolol significantly reduced the number of apoptotic and necrotic cells. Phentolamine administration appeared to increase the incidence of cell death among intestinal lymphocytes. Both drugs decreased the percentage of CD3+ intestinal lymphocytes. Our study suggests that catecholamines are not responsible for postexercise lymphocytopenia, but beta-adrenoceptor blockade may confer protection against exercise-induced apoptosis of intestinal lymphocytes.

The actuation of a biomimetic poly(vinyl alcohol)poly(acrylic acid) gel.

Active polymer gels expand and contract in response to certain environmental stimuli, such as the application of an electric field or a change in the pH level of the surroundings. This ability to achieve large, reversible deformations with no external mechanical loading has generated much interest in the use of these gels as biomimetic actuators and "artificial muscles". In previous work, a thermodynamically consistent finite-elastic constitutive model has been developed to describe the mechanical and actuation behaviours of active polymer gels. The mechanical properties were characterized by a free-energy function, and the model uses an evolving internal variable to describe the actuation state. In this work, an evolution law for the internal variable is determined from free actuation experiments on a poly(vinyl alcohol)poly(acrylic acid) (PVAPAA) gel. The complete finite-elastic/evolution law constitutive model is then used to predict the response of the PVA-PAA gel to isotonic and isometric loading and actuation. The model is shown to give relatively good agreement with experimental results.

BioGlue surgical adhesive for thoracic aortic repair during coagulopathy: efficacy and histopathology.

BACKGROUND: We hypothesized that induction of coagulopathy in sheep would model clinical needle hole and surgical bleeding from synthetic graft anastomoses, and that a new tissue bioadhesive (BioGlue) would control postoperative blood loss during surgical repair of the thoracic aorta. METHODS: Sheep were anticoagulated with aspirin and heparin. A bypass was made using end-to-side anastomoses of a graft to a partially occluded descending thoracic aorta. Experimental anastomoses (EXP, n = 9) were treated with BioGlue, and control anastomoses (CON, n = 5) were treated with Surgicel to gain intraoperative hemostasis. RESULTS: EXP animals exhibited significantly reduced postsurgical bleeding (CON median 955 mL versus EXP median 470 mL, p < 0.003), a reduced rate of blood loss over the first 2 postoperative hours (CON median 210 mL/hr versus EXP median 92.5 mL/hr, p < 0.006), and over the entire recovery period (CON median 158 mL/hr versus EXP median 86 mL/hr, p < 0.05), and reduced total blood loss (CON mean 1,497 +/- 691 mL versus EXP mean 668 +/- 285 mL, p < 0.008). On histologic examination of tissues explanted after 3 months, BioGlue was relatively inert and demonstrated a minimal inflammatory response. CONCLUSIONS: The use of BioGlue significantly reduced the volume and rate of postsurgical bleeding in a coagulopathic sheep model for thoracic aortic operations. Histopathologically, BioGlue generated only a minimal inflammatory response. This new surgical tissue bioadhesive should prove extremely beneficial for coagulopathic patients undergoing thoracic aortic or vascular procedures.

A novel technique in a sheep model for evaluating prosthetic heart valve performance.

There have been many various animal studies to evaluate the structural integrity and antithrombogenicity of prosthetic heart valves. We were interested in developing a novel sheep model to study the thrombogenicity of mechanical heart valves placed into the systemic circulation but without the need for cardiac bypass. Also, we wanted to minimize the risk ofparaplegia from complete thoracic aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a mechanical heart valve in parallel with the descending thoracic aorta. A valved conduit with a dacron tube graft sutured to the back end was fashioned. Employing partial aortic occlusion with a side-biting clamp, the proximal and distal ends were anastomosed in an end-to-side fashion. Once flow was confirmed through the graft, the native aorta was occulded with umbilical tape. The sheep received no postoperative anticoagulation. The median operative time and estimated blood loss (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was confirmed during the initial procedure, and there was no incidence of paraplegia postoperatively. Two animals expired shortly after extubation and at necropsy the valved conduits were patent with preserved valve function. The four survivors were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the valved conduits were evaluated in situ with ultrasound. In all cases, the valves had clot formation at the hinges, which prevented active movement of the leaflets. This novel in vivo technique provides an alternative in testing the thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of paraplegia in an animal that is extremely sensitive to complete aortic cross-clamp.