Gene Expression of Disease-related Genes in Alzheimer's Disease is Impaired by Tau Aggregation.

Neuronal hyperexcitability linked to an increase in glutamate signalling is a peculiar trait of the early stages of Alzheimer's disease (AD) and tauopathies, however, a progressive reduction in glutamate release follows in advanced stages. We recently reported that in the early phases of the neurodegenerative process, soluble, non-aggregated Tau accumulates in the nucleus and modulates the expression of disease-relevant genes directly involved in glutamatergic transmission, thus establishing a link between Tau instability and altered neurotransmission. Here we report that while the nuclear translocation of Tau in cultured cells is not impaired by its own aggregation, the nuclear amyloid inclusions of aggregated Tau abolish Tau-dependent increased expression of the glutamate transporter. Remarkably, we observed that in the prefrontal cortex (PFC) of AD patient brain, the glutamate transporter is upregulated at early stages and is downregulated at late stages. The Gene Set Enrichment Analysis indicates that the modulation of Tau-dependent gene expression along the disease progression can be extended to all protein pathways of the glutamatergic synapse. Together, this evidence links the altered glutamatergic function in the PFC during AD progression to the newly discovered function of nuclear Tau.

Contraceptive use and sexual function: a comparison of Italian female medical students and women attending family planning services.

Objectives: The aims of the study were to understand how education relates to contraceptive choice and how sexual function can vary in relation to the use of a contraceptive method.Methods: We surveyed female medical students and women attending a family planning service (FPS) in Italy. Participants completed an online questionnaire which asked for information on sociodemographics, lifestyle, sexuality and contraceptive use and also included items of the Female Sexual Function Index (FSFI).Results: The questionnaire was completed by 413 women (362 students and 51 women attending the FPS) between the ages of 18 and 30 years. FSFI scores revealed a lower risk of sexual dysfunction among women in the control group who did not use oral hormonal contraception. The differences in FSFI total scores between the two study groups, when subdivided by the primary contraceptive method used, was statistically significant (p < 0.005). Women using the vaginal ring had the lowest risk of sexual dysfunction, compared with all other women, and had a positive sexual function profile. In particular, the highest FSFI domain scores were lubrication, orgasm and satisfaction, also among the control group. Expensive contraception, such as long-acting reversible contraception, was not preferred by this young population, even though such methods are more contemporary and manageable. Compared with controls, students had lower compliance with contraception and a negative attitude towards voluntary termination of pregnancy.Conclusion: Despite their scientific knowledge, Italian female medical students were found to need sexual and contraceptive assistance. A woman's sexual function responds to her awareness of her body and varies in relation to how she is guided in her contraceptive choice. Contraceptive counselling is an excellent means to improve female sexuality.

A new long-term reversible contraception method: sexual and metabolic impact.

BACKGROUND: Data relating to the influence of hormonal contraception on sexual life are conflicting and mostly they refer to oral contraceptives. In this study we evaluated the effect of a long-acting contraceptive on sexual function, metabolism and bleeding pattern variations. METHODS: 23 women with a permanent partner and an active sexual life completed a specific questionnaire at the start of the study and after cycles 3 and 6 of contraceptive use; a blood sample was performed or metabolic evaluation and a "bleeding calendar" was compiled by the patients. CONCLUSION: There is an increase of quality and frequency of sexual function after 6 month of contraception; there aren't significant change in metabolic parameters and is detectable a modification of bleeding patterns.

[Idiopathic dilatation of the atria: a syndrome? Description of a case of idiopathic biatrial dilatation, review of the literature and a proposal for a pathogenetic interpretation]. / La dilatazione idiopatica degli atri: una sindrome? Descrizione di un caso di dilatazione idiopatica biatriale, revisione della letteratura e proposta di interpretazione patogenetica.

Idiopathic severe dilatation of bilateral atrial and urethero-pelvic systems was found in a 53-year-old woman. Degeneration of muscle fibers without inflammation is a constant feature of idiopathic atrial enlargement. Degenerative process can extensively involve atrial wall (generalized dilatation) or can be localized (aneurysmal dilatation). In both types of lesion clinical features are related to atrial arrhythmias and to compression on atrio-ventricular valves and ventricles by the enlarged atria. Only the outcome of the atrial arrhythmias can help to distinguish between the two conditions: development of irreversible atrial standstill in generalized dilatation and definitive restoration of sinus rhythm, following surgery, in aneurysmal dilatation. In each atrium, a different rate of incidence of the two types of dilatation has been documented in the literature: as for the right atrium, more than 40 cases of generalized dilatation have been reported and only 4 of the aneurysmal type. On the other hand, isolated left atrial enlargement was of aneurysmal type in all 30 reported cases. Biatrial dilatation was generalized in 7 cases and due to multiple aneurysms in a single case. The Authors support the hypothesis that idiopathic atrial dilatation could be due to a degenerative process affecting the atrial components derived from primitive atria, in which the muscular layer is structured into pectinate muscles. They also suggest to distinguish, even from the etiopathogenetic point of view, between aneurysmal dilatation (localized and fortuitous lesion) and generalized dilatation (diffuse degeneration of pectinate muscles). This distinction could well related with the different outcome of atrial arrhythmia in the two types of dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

[AQRS left axial deviation of more than -30 degrees and incomplete right branch block in isolated ventricular septal defects]. / Deviazione assiale sinistra di AQRS oltre -30 gradi e blocco di branca destra incompleto nei difetti isolati del setto ventricolare.

Electrocardiographic findings in five out of forty-three cases of isolated Ventricular Septal Defects (VSD) demonstrated incomplete Right Bundle Branch Block (RBBB) with left AQRS deviation of more than -30 degrees. These features are said to be characteristic of VSD of the Persistent Common Atrioventricular Canal type. However, in two of our five cases a defect of the Inlet Septum was documented angiographically; in the remaining three cases a defect of the peri-Membranous septum was clearly demonstrated. Moreover hemodynamic data in our patients indicate that right ventricular diastolic overload could not account for RBBB in all of the cases. The clinical importance derived from this experience is that ECG findings of RBBB and left AQRS deviation of more than -30 degrees are not necessarily associated with, and therefore do not represent certain proof of the presence of VSD of the A-V Canal type. The association of this ECG pattern with VSD's other than the A-V Canal type, as previously observed, appears to have an anatomic explanation, which however needs further substantiation through electrophysiologic studies.