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We aimed to analyze bone mineralization and the effect of different risk factors for osteoporosis in postmenopausal women. We studied 2,756 postmenopausal subjects out of ≥10,000 records from the ROIS registry in the frame of the PROF Project, a population study carried out in Salento (Taranto, Brindisi, Lecce) from 2009 to 2012. All subjects were assessed by phalangeal Quantitative Ultrasound (QUS) to evaluate their bone mineralization (assessed by Amplitude Dependent Speed of Sound, AD-SoS) and the association between demineralization and the presence of other conditions or risk factors. Mean age was 64±9.5 years and mean BMI was 28.7±3.5 Kg/m2. Pearson correlation analyses revealed a negative association between bone mineralization (AD-SoS) and BMI (P<0.001). By using multivariate logistic regression analysis, we observed significant values of Odds Ratios of osteoporosis (adjusted for age, physical activity and the use of drugs known to increase the risk of fractures) in subjects with diabetes and obesity: 1.39 (CI: 1,05–1,83) and 1.46 (CI: 1.20–1.78), respectively. A statistically significant linear trend of higher Odds Ratios of osteoporosis was found for increasing values of BMI. The percent change in the odds of vertebral fractures per single SD decrease of AD-SoS was 47% (P<0.001). Diabetes and obesity in postmenopausal women are likely to represent independent risk factors for osteoporosis. Phalangeal QUS showed a good power of predictivity in identifying subjects with vertebral fractures. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have suggested that nicotine could have beneficial effects on cognitive functioning. Objective: To explore the association between smoking and cognitive functioning in bipolar disorder and schizophrenia. Methods: Observational study. We analyzed data from 184 participants in 3 groups (61 healthy controls, 47 euthymic patients with bipolar-I disorder, 76 patients with clinically stable schizophrenia) assessed by a neuropsychological battery. Statistical analysis was performed comparing subgroups of smokers and non-smokers data. Both groups were demographic and clinically comparable. Results: Smoking rate was higher in participants with bipolar disorder and schizophrenia (X 2 =26.8, p=0.001). Bipolar Group: neuropsychological performance was similar in smokers (n=28) and non-smokers (n=19) except perseverative errors of the Wisconsin test, in which smokers performed significantly worse (t=−2.1, p=0,03). Schizophrenia group: smokers (n=46) performed significantly better than non-smokers (n=30) in the verbal fluency test (t=−2.46, p=0.046), finger tapping right (t=−2.19; p=0.03) and immediate (t=−2.84, p=0.006) and delayed recall (t=−2.59, p=0.01) of Rey figure test. Conclusions: This is the first study comparing these clinical groups. The global cognitive function in euthymic state was similar in both groups despite of smoking status. However, smoking could be associated with a worse executive function in bipolar disorder. In patients with schizophrenia smoking was associated with better performance in visual memory, verbal fluency and motor speed, but not attention. [ABSTRACT FROM AUTHOR]

Objective: To examine the role of leukemia inhibitory factor (LIF) during in vitro maturation (IVM) on human and mice cumulus expansion and mice oocyte competence by in vitro fertilization (IVF), culture, and embryo transfer (ET). Design: Prospective animal and human study. Setting: Serono laboratories and IVF clinic. Patient(s): Healthy women volunteers and 8-week-old female mice. Intervention(s): Cumulus compacted human and mice oocytes were matured in IVM media with and without recombinant follicle-stimulating hormone (FSH) and with and without LIF. Mice IVM oocytes with and without 0.2 IU/mL of recombinant FSH; or with and without recombinant FSH + LIF (0.1, 1.0, 1000.0 ng/mL) and ovulated oocytes were in vitro fertilized and cultured. We transferred 395 blastocysts to the uterine horn of 2.5-day pseudopregnant female mice. Main Outcome Measure(s): Cumulus expansion in human and mice oocytes, and two-cell rate, blastocyst rate, and delivered rate of live pups in mice. Result(s): In human and mouse oocytes, LIF induced cumulus expansion. When 1000 ng/mL of LIF was added in combination with recombinant FSH, a statistically significant increase in cleavage rate, embryo development rate, and birth rate was observed when compared with oocytes matured with FSH alone. Conclusion(s): Leukemia inhibitory factor induced cumulus expansion similarly in human and mouse cumulus–oocyte complexes, and recombinant FSH plus LIF supplementation during mouse IVM significantly improved oocyte competence as measured by cleavage rate, blastocyst development, and birth rate. [Copyright &y& Elsevier]

Abstract: Both neural development and prefrontal cortex function are known to be abnormal in schizophrenia and bipolar disorder. In order to test the hypothesis that these features may be related with genes that regulate neuronal migration, we analyzed two genomic regions: the lissencephaly critical region (chromosome 17p) encompassing the LIS1 gene and which is involved in human lissencephaly; and the genes related to the platelet-activating-factor, functionally related to LIS1, in 52 schizophrenic patients, 36 bipolar I patients and 65 normal control subjects. In addition, all patients and the 25 control subjects completed a neuropsychological battery. Thirteen (14.8%) patients showed genetic variations in either two markers related with lissencephaly or in the platelet-activating-factor receptor gene. These patients performed significantly worse in the Wisconsin Card Sorting Test–Perseverative Errors in comparison with patients with no lissencephaly critical region/platelet-activating-factor receptor variations. The presence of lissencephaly critical region/platelet-activating-factor receptor variations was parametrically related to perseverative errors, and this accounted for 17% of the variance (P=0.0001). Finally, logistic regression showed that poor Wisconsin Card Sorting Test–Perseverative Errors performance was the only predictor of belonging to the positive lissencephaly critical region/platelet-activating-factor receptor group. These preliminary findings suggest that the variations in genes involved in neuronal migration predict the severity of the prefrontal cognitive deficits in both disorders. [Copyright &y& Elsevier]

Follicle-stimulating hormone receptor (FSHR) plays a key role in reproduction through the activation of multiple signaling pathways. Low molecular weight (LMW) ligands composed of biased agonist properties are highly valuable tools to decipher complex signaling mechanisms as they allow selective activation of discrete signaling cascades. However, available LMW FSHR ligands have not been fully characterized yet. In this context, we explored the pharmacological diversity of three benzamide and two thiazolidinone derivatives compared to FSH. Concentration/activity curves were generated for Gαs, Gαq, Gαi, β-arrestin 2 recruitment, and cAMP production, using BRET assays in living cells. ERK phosphorylation was analyzed by Western blotting, and CRE-dependent transcription was assessed using a luciferase reporter assay. All assays were done in either wild-type, Gαs or β-arrestin 1/2 CRISPR knockout HEK293 cells. Bias factors were calculated for each pair of read-outs by using the operational model. Our results show that each ligand presented a discrete pharmacological efficacy compared to FSH, ranging from super-agonist for β-arrestin 2 recruitment to pure Gαs bias. Interestingly, LMW ligands generated kinetic profiles distinct from FSH (i.e., faster, slower or transient, depending on the ligand) and correlated with CRE-dependent transcription. In addition, clear system biases were observed in cells depleted of either Gαs or β-arrestin genes. Such LMW properties are useful pharmacological tools to better dissect the multiple signaling pathways activated by FSHR and assess their relative contributions at the cellular and physio-pathological levels. [ABSTRACT FROM AUTHOR]