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Adjuvant chemotherapy is recommended in high-risk breast cancer. However, no universally accepted guidelines exist on pre-chemotherapy assessment. In particular, the number and frequency of medical visits vary according to each institution's policy. We hypothesised that the Edmonton Symptom Assessment Scale (ESAS) may have a favourable impact on the pre-treatment assessment in candidates for adjuvant chemotherapy.To investigate whether the ESAS can be used to safely reduce the number of medical visits in women with breast cancer undergoing adjuvant chemotherapy.In a retrospectively prospective matched-pair analysis, 100 patients who completed the ESAS questionnaire before administration of adjuvant chemotherapy (ESAS Group) were compared with 100 patients who underwent chemotherapy according to the traditional modality, without ESAS (no-ESAS Group). Patients of the ESAS Group received additional visits before treatment if their ESAS score was3. The primary endpoint was the total number of medical visits during the entire duration of the chemotherapy period. The secondary endpoints were the occurrence of severe complications (grade 3-4) and the number of unplanned visits during the chemotherapy period.The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group (ageThe ESAS score may safely reduce the number of medical visits in candidates for adjuvant chemotherapy for early breast cancer. Our results suggest that the ESAS score may be used for selecting a group of breast cancer patients for whom it is safe to reduce the number of medical visits in the setting of adjuvant chemotherapy. This may translate into several advantages, such as a more rational utilization of human resources and a possible reduction of coronavirus pandemic infection risk in oncologic patients.

Purpose To develop and characterize a mouse model of spontaneous recurrent seizures following nerve agent-induced status epilepticus (SE) and test the efficacy of existing antiepileptic drugs. Methods SE was induced in telemeterized male C57Bl6/J mice by soman exposure, and electroencephalographic activity was recorded for 4–6 weeks. Mice were treated with antiepileptic drugs (levetiracetam, valproic acid, phenobarbital) or corresponding vehicles for 14 d after exposure, followed by 14 d of drug washout. Survival, body weight, seizure characteristics, and histopathology were used to characterize the acute and chronic effects of nerve agent exposure and to evaluate the efficacy of treatments in mitigating or preventing neurological effects. Results Spontaneous recurrent seizures manifested in all survivors, but the number and frequency of seizures varied considerably among mice. In untreated mice, seizures became longer over time. Moderate to severe histopathology was observed in the amygdala, piriform cortex, and CA1. Levetiracetam provided modest improvements in neurological parameters such as reduced spike rate and improved histopathology scores, whereas valproic acid and phenobarbital were largely ineffective. Conclusions This model of post-SE spontaneous recurrent seizures differs from other experimental models in the brief latency to seizure development, the occurrence of seizures in 100 % of exposed animals, and the lack of damage to CA4/dentate gyrus. It may serve as a useful tool for rapidly and efficiently screening novel therapies that would be effective against severe epilepsy cases.

Autophagy is an evolutionarily conserved pathway mediating the breakdown of cellular proteins and organelles. Emphasizing its pivotal nature, autophagy dysfunction contributes to many diseases; nevertheless, development of effective autophagy modulating drugs is hampered by fundamental deficiencies in available methods for measuring autophagic activity, or flux. To overcome these limitations, we introduced the photoconvertible protein Dendra2 into the MAP1LC3B locus of human cells via CRISPR/Cas9 genome editing, enabling accurate and sensitive assessments of autophagy in living cells by optical pulse labeling. High-content screening of 1,500 tool compounds provided construct validity for the assay and uncovered many new autophagy modulators. In an expanded screen of 24,000 diverse compounds, we identified additional hits with profound effects on autophagy. Further, the autophagy activator NVP-BEZ235 exhibited significant neuroprotective properties in a neurodegenerative disease model. These studies confirm the utility of the Dendra2-LC3 assay, while simultaneously highlighting new autophagy-modulating compounds that display promising therapeutic effects.

The opioid epidemic has been declared a US national public health emergency. Discrepancies in the rates of abuse and access to treatment exist among non-white minorities. A narrative literature review evaluated the minority racial disparities in opioid use, abuse, and care in the US. Racial disparities in the prescription of opioid-containing compounds are dramatic with the non-white individuals being prescribed at half the rate. Historical and cognitive biases may have insulated the non-white minorities, while the minorities have limited access to treatment. Physician bias, media portrayal of opioid abuse disorders, and governmental regulation are a polyfactorial root of racial inequity in the opioid epidemic. As part of the national response, addressing these issues will be an important factor in curbing this epidemic.

The opioid epidemic has been declared a US national public health emergency. Discrepancies in the rates of abuse and access to treatment exist among non-white minorities. A narrative literature review evaluated the minority racial disparities in opioid use, abuse, and care in the US. Racial disparities in the prescription of opioid-containing compounds are dramatic with the non-white individuals being prescribed at half the rate. Historical and cognitive biases may have insulated the non-white minorities, while the minorities have limited access to treatment. Physician bias, media portrayal of opioid abuse disorders, and governmental regulation are a polyfactorial root of racial inequity in the opioid epidemic. As part of the national response, addressing these issues will be an important factor in curbing this epidemic.

Though millions of people practice yoga to reduce stress and improve their mood, it is unclear which aspect of yoga is responsible for these effects. To investigate relevant aspects, or “limbs” of yoga, participants who were novices in the practice of yoga engaged in a single yoga manipulation (i.e., poses, breath work, meditation, or listening to a lecture about yoga) for 20 min before experiencing a mild stressor. Participants’ heart rate, blood pressure, mood, and anxiety level were assessed, both immediately after the yoga manipulation and after the mild stressor. The 20-min yoga manipulation did not differentially affect any of the measures, including participants’ stress response after the mild stressor. Results are discussed regarding the individual components of a yoga practice.

Melkersson-Rosenthal syndrome is a rare granulomatous neuro-mucocutaneous systemic disease that is characterized by relapsing peripheral facial paralysis, orofacial edema and fissured tongue. The disease etiology is still not well known, but it has been hypothesized that a possible role is played by various causal agents such as infectious diseases, genetic causes, allergic conditions, benign lymphogranulomatosis, various associations with other pathological conditions, particularly with immune-mediated diseases and food contact allergies. In this report we describe the case of a woman, 42 years old, with psoriatic arthritis who developed neurological episodes related to MRS after treatment with anti-TNF therapy. This finding further supports the hypothesis that TNF-α blockade, and particularly the use of the TNF-α receptor, could trigger the development of granulomatous lesions in predisposed patients. The case we report further sustains the importance for the clinician to take into account this potential adverse event in patients receiving anti-TNF-α therapies.

INTRODUCTION: Traffic-related air pollution causes fatty liver, inflammation, and fibrosis in animal models, but there have been few studies in humans. OBJECTIVES: To test the hypothesis that traffic-related air pollution causes non-alcoholic fatty liver disease (NAFLD) and increased markers for non-alcoholic steatohepatitis (NASH); and that NAFLD increases liver susceptibility to increased NASH risk. METHODS: Data collected prospectively from 74 overweight or obese children were obtained from the Yale Pediatric Obesity Clinic. Traffic-related air pollution was characterized as vehicle traffic volume on major roads within a one kilometer residential buffer, and as residential nitrogen dioxide (NO(2)) exposure. Outcomes were hepatic fat fraction (HFF) measured by magnetic resonance imaging, liver enzymes using standard assays, and plasma cytokeratin-18 (CK-18) by immunosorbent assays. RESULTS: Significant non-linear relationships with air pollution and CK-18 were found. Plasma CK-18 at follow-up increased from approximately 150U/L to almost 200U/L as residential traffic volume increased from 220,000vehicle-km to 330,000vehicle-km, after adjustment for baseline CK-18, age and gender. Among patients with NAFLD at baseline, CK-18 increased from 140U/L to 200U/L (a 1.5 standard deviation increase in CK-18) as NO(2) increased from 8ppb to 10ppb. CONCLUSIONS: Traffic-related air pollution was associated with CK-18. Effects were larger in children with pre-existing NAFLD at study entry.

Muscari A, Puddu GM, Santoro N, Zoli M. A simple scoring system for outcome prediction of ischemic stroke. Acta Neurol Scand: 2011: 124: 334–342. © 2011 John Wiley & Sons A/S. Objectives – According to most existing models, a computer is usually needed for predicting stroke outcome. Our purpose was to construct a simple and reliable prognostic scale not requiring the use of a calculating machine. Materials and Methods – The scale [the Bologna Outcome Algorithm for Stroke (BOAS)] was obtained in 221 patients with ischemic stroke not undergoing thrombolysis and was then validated in a test group of 100 different patients. Outcome was assessed at 9 months as the number of dependent or dead patients (modified Rankin scale – mRS > 2). Results – By a preliminary systematic univariate analysis, 25 of 415 baseline variables were found to be associated with a mRS > 2 independently of stroke severity and age. Subsequent multivariable analyses led to a final model based on five dichotomous risk factors (RF): National Institutes of Health Stroke Scale score ≥10, age ≥78, need of urinary catheter, oxygen administration, and persistence of upper limb paralysis at discharge from stroke unit. The patients with two or more RF (53%) had a mRS > 2 in 91% of cases and were dead in 42% of cases. With 0–1 RF, the two percentages were 24% and 2%, respectively (overall accuracy of prediction 83.9%, area under ROC curve [AUC] 0.891). In the test group, the accuracy was 79.0% and the AUC was 0.839. Conclusions – The need of urinary catheter, oxygen administration, and persistence of upper limb paralysis, together with stroke severity and advanced age, allow a simple and accurate prediction of dependency or death after ischemic stroke.

Background: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. Methods: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. Results: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression

Various instruments based on acquisition and elaboration of images of pigmented skin lesions have been developed in an attempt to in vivo establish whether a lesion is a melanoma or not. Although encouraging, the response of these instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and fluorescence imaging, cannot currently replace the well-established diagnostic procedures. However, in place of the approach to instrumentally assess the diagnosis of the lesion, recent studies suggest that instruments should rather reproduce the assessment by an expert clinician of whether a lesion has to be excised or not. The aim of this study was to evaluate the performance of a spectrophotometric system to mimic such a decision. The study involved 1794 consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions excised for histopathological diagnosis and 348 patients with 1940 non-excised lesions because clinically reassuring. Images of all these lesions were acquired in vivo with a multispectral imaging system. The data set was randomly divided into a train (802 reassuring and 1003 excision-needing lesions, including 139 melanomas), a verify (464 reassuring and 439 excision-needing lesions, including 72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions, including 76 melanomas). An artificial neural network (ANN(1)) was set up to perform the classification of the lesions as excision-needing or reassuring, according to the expert clinicians' decision on how to manage each examined lesion. In the independent test set, the system was able to emulate the clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462 correctly classified as excision-needing lesions, 72 (95%) were melanomas. No major variations in receiver operating characteristic curves were found between the test and the train/verify sets. On the same data set, a further artificial neural network (ANN(2)) was then architected to perform classification of the lesions as melanoma or non-melanoma, according to the histological diagnosis. Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be significantly better in the classification of reassuring lesions than ANN(2). This study suggests that multispectral image analysis and artificial neural networks could be used to support primary care physicians or general practitioners in identifying pigmented skin lesions that require further investigations.

Resume Les bisphosphonates sont utilises pour traiter non seulement l'osteoporose, mais aussi d'autres pathologies caracterisees par une resorption osseuse accrue, comme la maladie de Paget, l'hypercalcemie maligne du myelome, les metastases osseuses lytiques et la dysplasie fibreuse des os. Le principal effet biologique des bisphosphonates consiste en une reduction du remodelage osseux liee a une inhibition de l'activite des osteoclastes. Toutefois, de nombreuses observations cliniques et experimentales montrent que les bisphosphonates ont des effets extraosseux. Par exemple, en dehors de leur action sur les cellules osseuses, les bisphosphonates exercent un effet immunomodulateur sur les cellules immunitaires, influencant ainsi la production de cytokines pro- et anti-inflammatoires et modifiant l'expression des molecules qui participent aux phenomenes immunitaires et a la reponse anti-inflammatoire. Bien que les donnees soient contradictoires, plusieurs etudes decrivent un effet favorable des bisphosphonates sur l'evolution des rhumatismes inflammatoires chroniques, laissant penser que les indications cliniques de ces molecules pourraient s'etendre prochainement.

The objective of these three studies was to evaluate the effects of influenza vaccination on influenza-like illness (ILI), attack rates and indirect costs for the employers. They were observational studies involving two groups, vaccinated and non-vaccinated, retrospective in Argentina and prospective in Malaysia and Colombia. Data collected covered socio-economic and health status information, data on ILI symptoms and sick leaves. Vaccine adverse events were reported when they occurred. Cost–benefit analyses were performed from the employer perspective using labour costs and operating income, absenteeism and attendance were considered. Sample size varied from 528 to 1022 subjects with well-balanced vaccinated and non-vaccinated groups. In various epidemiological and influenza strains matching, vaccination effectiveness rates on ILI occurrence varied from 68.5% to 84.8%. Two scenarios were presented and the results of the cost–benefit analysis showed systematic net cost–savings per vaccinated employee of US$73.1–240 in Argentina, US$6.45–89.3 in Colombia and US$39.9–734 in Malaysia. This study showed that influenza has significant impact on productivity in different countries and industrial sectors facing epidemiological conditions and risk factors for influenza. In all studies, influenza vaccination showed high effectiveness rates leading to important cost–savings for the employer.

The objective of this study was to evaluate the effects of a 9-year influenza vaccination program measured in terms of health and economic benefits. A retrospective observational study was conducted among the workforce of an Argentinean chemical company from January 1994 to December 2002, involving two cohorts, vaccinated and nonvaccinated. The occupational health database was used to collect socioeconomic and health status information, occurrence and duration of ILI symptoms and sick leaves. Vaccine's adverse events were reported when occurred. Cost–benefit analyses were performed from the employer's perspective, monetarizing absenteeism and attendance with salary values and operating income. Costs of vaccination included vaccine price, cost of administration and adverse events if occurred. The total number of employees varied from 800 to 520 employees. An average of 57% were vaccinated and 43% not vaccinated; the attack rates of ILI were, respectively, 5.3±1.25% versus 26.2±7.02%, with presence of usual symptoms and fever in 100% of the reported ILI. Overall, the effectiveness rate of reducing the occurrence of ILI symptoms was 75.9±9.08%. The mean annual cost savings was 200 ARS (Argentinean pesos) per employee vaccinated. This study showed that influenza vaccination had significant impact on ILI occurrence and leads to important cost savings for the employer.

Mean platelet volume (MPV) has been associated with the prognosis in stroke patients. However, its spontaneous variability during the acute phase of the disease is unknown. Materials and Methods - One hundred and thirty-seven patients with ischemic stroke, aged 75.4+/-11.0 (SD) years, were classified according to several criteria: National Institutes of Health Stroke Scale (NIHSS) score, maximum lesion diameter on CT scan, Oxfordshire Community Stroke Projects (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) categories. Platelet parameters were determined 1.2 days after the onset of symptoms, and after 3.0 further days.The initial MPV was higher in non-lacunar than lacunar strokes (8.30+/-1.10 vs. 7.95+/-0.79 fl, P=0.04), and correlated with the sampling delay with respect to the onset of symptoms, especially in the strokes with lesions=4 cm (r=0.39, P=0.009), NIHSS=11 (r=0.35, P=0.02) and of cardioembolic origin (r=0.35, P=0.01). Subsequently a late MPV increment was observed in the remaining categories: from 8.20 to 8.38 fl (P=0.02) in the strokes with lesions4 cm, from 8.11 to 8.31 fl (P=0.01) in the presence of an NIHSS11 and from 8.20 to 8.61 fl (P=0.03) when the occlusion of a large artery was involved.Platelet volume is not stable during the acute phase in non-lacunar ischemic strokes, as it increases early in the most severe forms, and later in the remaining subtypes. The release of large and more reactive platelets may contribute to the thrombophilic state associated with ischemic events.

In the last years there is an increasing interest for the question of whether patients treated with antitumour necrosis factor-α (TNF-α) agents are at increased risk of infections. We aim to assess the possible role of anti-TNF-α treatment in the increase of the risk of infections in a population of patients affected by rheumatoid arthritis or psoriatic arthritis.We analyzed data of patients affected by chronic arthritis treated with anti-TNF-α to investigate the risk of infections. Statistical analysis was done using STATA software.The odds ratio for patients treated with anti-TNF-α who developed infections was 1.61 (CI: 0.88, 2.92, P0.11). We found an odds ratio of 1.41 (CI: 0.74, 2.68, P0.29) in patients treated with anti-TNF-α who developed urinary tract infection, and an odds ratio of 2.63 (CI: 0.31, 22.19, P0.37) in patients treated with anti-TNF-α who developed herpes zoster.These results seems to indicate a role of anti-TNF-α treatment in the risk of infection. Nevertheless, our results are not statistically significant probably because the sample sizes are too small and the time of observation among patients is variable. Moreover, other confounding factors may be gender, age and the different degrees of disease activity and comorbidity. In conclusion, limitations in the study size and design preclude definitive conclusions about the question of whether patients treated with anti-TNF-α agents are at increased risk of infections. The performance of additional research are needed to answer this question.

Atomic force microscopy (AFM) has been used to observe modifications induced by a 50-Hz 2-mT sinusoidal magnetic field on human B-lymphoblastoid cells (Raji). Cells exposed up to 64 h showed a drastic decrease in cell height during the first 13 h, reflecting the disappearance of microvilli, and a slower variation of the same parameter during the following 51 h together with a widening and loss of the cell's domed shape that corresponds to modifications at the cytoskeleton level.

Introduction Estetrol (E4), a naturally occurring estrogen only produced by the human fetal liver, is being evaluated in human studies for potential use in contraception and menopausal care. The present study was designed to profile E4 in the central nervous system, to assess the in vivo effects of E4 administration on allopregnanolone (AP) synthesis in specific brain structures and to evaluate whether E4 has synergic or antagonistic effects on estradiol-mediated AP synthesis. Material and methods Intact female adult rats received different doses of E4, and ovariectomized OVX rats received different doses of E4 or E2V or combinations of both drugs. The concentrations of AP were assessed in the frontal and parietal cortex, hippocampus, hypothalamus, anterior pituitary, and serum. Results E4 did not alter AP in intact animals in any region. E4 at a dosage of 5 mg/kg/day increased AP levels in different brain areas and in the serum of OVX animals. However, in the presence of estradiol, E4 showed an estrogen-antagonistic effect on the brain and serum levels of AP. Conclusion E4 increases the CNS and peripheral levels of AP, behaving as a weak estrogen-agonist in OVX rats. The antagonistic effect observed with E2V co-administration further profile E4 as a natural SERM.

Summary Selective targeting of drugs or oligonucleotide for the treatment of viral diseases or cancer is the objective of new strategies that pursue therapy optimization and reduction of toxicity. In this work we report two protocols based on encapsulation of antihuman immunodeficiency virus drugs within targeted liposomes or erythrocytes. Both have been shown to be effective for the specific delivery of drugs or oligonucleotide in the treatment of viral infection.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system and peripheral nervous system. Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids during fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. The brain metabolism of synthetic progestins and the implications of DHEA treatment in postmenopausal women will also be discussed.

The aim of this paper was to evaluate by clinical and non-invasive instrumental evaluations, the efficacy and the tolerance of a cosmetic slimming treatment for menopausal women used topically (for at least 3 years) under dermatological control.A controlled double blind, randomised study was performed to compare the slimming efficacy of the cosmetic slimming treatment versus placebo after 4 weeks of treatment.Cosmetic slimming treatment twice a day for 4 weeks reduced abdomen and hips fat, with no significant variation in body weight in comparison with the placebo.The present study evidenced the clinical effectiveness and women satisfaction of a slimming treatment specifically studies for postmenopausal adipose tissue with potential interesting consequences on measures of quality of life and on health-care programs.

The purpose of this study was to evaluate whether or not, using sensitive analytical methods for the measurement of coagulation and fibrinolysis enzyme activity, there was a hypercoagulable state in patients with melanoma, and whether differences existed between those with or without metastases. Seventy-one patients were studied, 45 with localized tumors (stages Ia and Ib) and 26 with metastases (stages II-IV). Plasma level of activated factor VII, prothrombin fragment 1 + 2, thrombin-antithrombin complex, fibrinopeptide A, plasmin-antiplasmin complex and D-dimer were much higher in the whole group of 71 patients than in 45 controls with benign nevi. However, when melanoma patients with or without metastases were compared, there were smaller differences, with only thrombin-antithrombin complex, plasmin-antiplasmin and D-dimer significantly higher in metastatic melanoma. These results indicate that in patients carrying a tumor endowed with high procoagulant activity in vitro, there is a laboratory picture of hypercoagulability with secondary hyperfibrinolysis in vivo. However, differences between patients with localized and metastatic tumors for markers of hypercoagulability are not striking, in spite of the fact that metastatic cells support greater coagulant activity than primary cells in vitro.

The presence of high-affinity brain-derived neurotrophic factor receptor Trk B in mouse and in human fetal oocytes, together with the presence of neurotrophins in human follicular fluid suggests a paracrine role for brain-derived neurotrophic factor (BDNF) in female biology. This study aims to evaluate if BDNF is present and quantitatively determined in human menstrual blood and endometrium. Twenty-one women were studied and subdivided in two groups: A, 11 fertile women (27 ± 2 days cycle length) and B, 10 anovulatory women and/or women with inadequate luteal phase (36 ± 2 days cycle length). In fertile women menstrual BDNF levels was higher than plasma (679.3 ± 92.2 vs 301.9 ± 46.7 pg/ml p

In the graph searching game the opponents are a set of searchers and a fugitive in a graph. The searchers try to capture the fugitive by applying some sequence of moves that include placement, removal, or sliding of a searcher along an edge. The fugitive tries to avoid capture by moving along unguarded paths. The search number of a graph is the minimum number of searchers required to guarantee the capture of the fugitive. In this paper, we initiate the study of this game under the natural restriction of connectivity where we demand that in each step of the search the locations of the graph that are clean (i.e. non-accessible to the fugitive) remain connected. We give evidence that many of the standard mathematical tools used so far in classic graph searching fail under the connectivity requirement. We also settle the question on the price of connectivity, that is, how many searchers more are required for searching a graph when the connectivity demand is imposed. We make estimations of the price of connectivity on general graphs and we provide tight bounds for the case of trees. In particular, for an n-vertex graph the ratio between the connected searching number and the non-connected one is O(logn) while for trees this ratio is always at most 2. We also conjecture that this constant-ratio upper bound for trees holds also for all graphs. Our combinatorial results imply a complete characterization of connected graph searching on trees. It is based on a forbidden-graph characterization of the connected search number. We prove that the connected search game is monotone for trees, i.e. restricting search strategies to only those where the clean territories increase monotonically does not require more searchers. A consequence of our results is that the connected search number can be computed in polynomial time on trees, moreover, we show how to make this algorithm distributed. Finally, we reveal connections of this parameter to other invariants on trees such as the Horton-Strahler number. © 2012 Elsevier Inc.

The hypothalamic-pituitary-ovarian (HPO) axis goes through a series of complicated, but well coordinated changes as a women enters the menopausal transition. The reproductive consequences of these changes are obvious, but there are also a number of general health consequences as well. As our understanding of the complex inter-workings of the HPO axis evolves, we will be better able to predict menopausal events and create strategies and treatments to optimize women's health as the progress through the menopausal transition.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system (CNS) and peripheral nervous system (PNS). Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another therapeutical strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach is so far hampered by the lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by peripheral glands. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neuro-steroids during the fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. Brain metabolism of synthethic progestins and the implication of dehydroepiandrosterone (DHEA) treatment in post-menopausal women will be also discussed.

Objectives Statins have antioxidant, anti-inflammatory, anticoagulant, and profibrinolytic properties that might play a useful role in the acute phase of ischemic stroke. This pilot study assessed the possible neuroprotective action of high-dose atorvastatin administration during the first week after an ischemic stroke, to obtain data for planning a wider multicenter study. Methods Sixty-two patients with ischemic stroke, aged 75.3 (SD, ±11.9) years (68% women), were randomized into a placebo (n = 31) and an atorvastatin 80 mg/d (n = 31) group. The double-blind treatment lasted 7 days. The primary end point was a decrease of National Institutes of Health Stroke Scale score of 4 points or higher after 7 days. Infarct volume measured on computed tomographic scan after 3 days and a modified Rankin Scale of less than 2 at 3 months were secondary end points. Results There was no difference in the primary end point between the 2 groups (odds ratio, atorvastatin vs placebo, 0.74; 95% confidence interval, 0.26-2.17). Infarct volume also was similar in the 2 groups. Instead, there were more patients with modified Rankin Scale of less than 2 at 3 months in the atorvastatin than in the placebo group (adjusted odds ratio, 6.7; 95% confidence interval, 1.0-45.0; P = 0.05). This prevalence concerned only the subgroup with mild strokes (National Institutes of Health Stroke Scale, ≤10; 53.8% vs 15.4%, respectively; P = 0.04). Atorvastatin was well tolerated. Conclusions This pilot study was unable to show any short-term benefit of atorvastatin during the acute phase of ischemic stroke. However, it suggested a possible favorable functional effect at 3 months in the least severe strokes, which could be the primary end point for a future multicenter trial.

Objectives – According to most existing models, a computer is usually needed for predicting stroke outcome. Our purpose was to construct a simple and reliable prognostic scale not requiring the use of a calculating machine. Materials and Methods – The scale (the Bologna Outcome Algorithm for Stroke-BOAS) was obtained in 221 patients with ischemic stroke not undergoing thrombolysis, and was then validated in a test group of 100 different patients. Outcome was assessed at 9 months as the number of dependent or dead patients (modified Rankin scale – mRS >2). Results – By a preliminary systematic univariate analysis, 25 out of 415 baseline variables were found to be associated with a mRS>2 independently of stroke severity and age. Subsequent multivariable analyses led to a final model based on 5 dichotomous risk factors (RF): National Institutes of Health Stroke Scale score >=10, age >=78 years, need of urinary catheter, oxygen administration and persistence of upper limb paralysis at discharge from stroke unit. The patients with 2 or more RF (53%) had a mRS>2 in 91% of cases, and were dead in 42% of cases. With 0-1 RF the two percentages were 24% and 2% respectively (overall accuracy of prediction 83.9%, area under ROC curve [AUC] 0.891). In the test group the accuracy was 79.0% and the AUC was 0.839. Conclusions – The need of urinary catheter, oxygen administration and persistence of upper limb paralysis, together with stroke severity and advanced age, allow a simple and accurate prediction of dependency or death after ischemic stroke.

A nosocomial outbreak of 2009 pandemic influenza A(H1N1), with eight confirmed cases, occurred in a paediatric oncology ward in Italy, in October/November 2009. The fact that one case was infected despite being isolated and without contact to a symptomatic patient, hints towards potential transmission through a health care worker (HCW) and underlines the importance of vaccination of HCW who are involved in the care of critically ill patients.