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Objective: The objective of this study was to analyse the use of bisphosphonates in women with rheumatoid arthritis (RA) in the Canary Islands. Material and methods: This multicentre observational study included women aged 50 years or over. At a single visit, demographic variables and those relating to the RA, history of fragility fractures, use of corticoids, performance of bone densitometry (DXA) and current treatment with bisphosphonates were recorded. The simplified FRAX ® tool was used and the recommendations of the American College of Rheumatology (ACR) for the prophylaxis of osteoporosis with corticoids were applied. Results: 192 women were included, with an average age of 62 years. A total of 91 (48%) patients were receiving corticoids; 17 of these (9%) had suffered a fracture; 123 (66%) had had a DXA; and 52 (28%) were taking bisphosphonates (70% of the patients with osteoporosis or fracture and 45% of those with criteria for prophylactic use of corticoids for osteoporosis). Those factors having a significant association with the use of bisphosphonates were age, duration of the disease, the HAQ functional capacity questionnaire, the risk of fracture determined by FRAX®, treatment with corticoids, history of fracture and the previous performance of DXA. In the multivariate study only the DXA (p=0.03) and history of fracture (p=0.02) were significantly associated. Conclusions: In postmenopausal women from the Canary Islands with RA the prescription of bisphosphonates could conform better to the guidelines, especially in patients receiving treatment with corticoids. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to analyse the use of bisphosphonates in women with rheumatoid arthritis (RA) in the Canary Islands. Material and methods: This multicentre observational study included women aged 50 years or over. At a single visit, demographic variables and those relating to the RA, history of fragility fractures, use of corticoids, performance of bone densitometry (DXA) and current treatment with bisphosphonates were recorded. The simplified FRAX ® tool was used and the recommendations of the American College of Rheumatology (ACR) for the prophylaxis of osteoporosis with corticoids were applied. Results: 192 women were included, with an average age of 62 years. A total of 91 (48%) patients were receiving corticoids; 17 of these (9%) had suffered a fracture; 123 (66%) had had a DXA; and 52 (28%) were taking bisphosphonates (70% of the patients with osteoporosis or fracture and 45% of those with criteria for prophylactic use of corticoids for osteoporosis). Those factors having a significant association with the use of bisphosphonates were age, duration of the disease, the HAQ functional capacity questionnaire, the risk of fracture determined by FRAX®, treatment with corticoids, history of fracture and the previous performance of DXA. In the multivariate study only the DXA (p=0.03) and history of fracture (p=0.02) were significantly associated. Conclusions: In postmenopausal women from the Canary Islands with RA the prescription of bisphosphonates could conform better to the guidelines, especially in patients receiving treatment with corticoids. [ABSTRACT FROM AUTHOR]

Background: Oxytocin (OT) is produced by granulosa cells (GCs) of pre-ovulatory ovarian follicles and the corpus luteum (CL) in some mammalian species. Actions of OT in the ovary have been linked to luteinization, steroidogenesis and luteolysis. Human IVF-derived (h)GCs possess a functional OT receptor (OTR), linked to elevation of intracellular Ca(2+), but molecular identity of the receptor for OT in human granulosa cells (hGCs) and down-stream consequences are not known.Methods and Results: RT-PCR, sequencing and immunocytochemistry identified the genuine OTR in hGCs. OT (10 nM-10 microM) induced elevations of intracellular Ca(2+) levels (Fluo-4 measurements), which were blocked by tocinoic acid (TA; 50 microM, a selective OTR-antagonist). Down-stream effects of OTR-activation include a concentration dependent decrease in cell viability/metabolism, manifested by reduced ATP-levels, increased caspase3/7-activity (P < 0.05) and electron microscopical signs of cellular regression. TA blocked all of these changes. Immunoreactive OTR was found in the CL and GCs of large and, surprisingly, also small pre-antral follicles of the human ovary. Immunoreactive OTR in the rhesus monkey ovary was detected in primordial and growing primary follicles in the infantile ovary and in follicles at all stages of development in the adult ovary, as well as the CL: these results were corroborated by RT-PCR analysis of GCs excised by laser capture microdissection.Conclusions: Our study identifies genuine OTRs in human and rhesus monkey GCs. Activation by high levels of OT leads to cellular regression in hGCs. As GCs of small follicles also express OTRs, OT may have as yet unknown functions in follicular development. [ABSTRACT FROM AUTHOR]

The excitatory tone to gonadotrophin-releasing hormone (GnRH) neurones is a critical component underlying the pubertal increase in GnRH secretion. However, the homeostatic mechanisms modulating the response of GnRH neurones to excitatory inputs remain poorly understood. A basic mechanism of neuronal homeostasis is the Na+,K+-ATPase-dependent restoration of Na+ and K+ transmembrane gradients after neuronal excitation. This activity is reduced in a mouse model of Rett syndrome (RTT), a neurodevelopmental disorder in which expression of FXYD1, a modulator of Na+,K+-ATPase activity, is increased. We now report that the initiation, but not the completion of puberty, is advanced in girls with RTT, and that, in rodents, FXYD1 may contribute to the neuroendocrine regulation of female puberty by modulating GnRH neuronal excitability. Fxyd1 mRNA abundance reaches maximal levels in the female rat hypothalamus by the fourth postnatal week of life (i.e., around the time when the mode of GnRH secretion acquires an adult pattern of release). Although Fxyd1 mRNA expression is low in the hypothalamus, approximately 50% of GnRH neurones contain Fxyd1 transcripts. Whole-cell patch recording of GnRH–EGFP neurones revealed that the neurones of Fxyd1-null female mice respond to somatic current injections with a lower number of action potentials than wild-type cells. Both the age at vaginal opening and at first oestrous were delayed in Fxyd1 −/− mice, but adult reproductive capacity was normal. These results suggest that FXYD1 contributes to facilitating the advent of puberty by maintaining GnRH neuronal excitability to incoming transsynaptic stimulatory inputs. [ABSTRACT FROM AUTHOR]

Transsynaptic and glial–neuronal communication are important components of the mechanism underlying the pubertal activation of luteinizing hormone-releasing hormone (LHRH) secretion. The molecules required for the architectural organization of these cell–cell interactions have not been identified. We now show that the hypothalamus of the prepubertal female rhesus monkey expresses a multiplicity of genes encoding three families of adhesion/signalling proteins involved in the structural definition of both neurone-to-neurone and bi-directional neurone–glia communication. These include the neurexin/neuroligin (NRX/NRL) and protocadherin-α (PCDHα) families of synaptic specifiers/adhesion molecules, and key components of the contactin-dependent neuronal–glial adhesiveness complex, including contactin/F3 itself, the contactin-associated protein-1 (CASPR1), and the glial receptor protein tyrosine phosphataseβ. Prominently expressed among members of the NRX family is the neurexin isoform involved in the specification of glutamatergic synapses. Although NRXs, PCDHαs and CASPR1 transcripts are mostly detected in neurones, the topography of expression appears different. NRX1 mRNA-containing neurones are scattered throughout the hypothalamus, PCDHα mRNA transcripts appear more abundant in neurones of the arcuate nucleus and periventricular region, and neurones positive for CASPR1 mRNA exhibit a particularly striking distribution pattern that delineates the hypothalamus. Examination of LHRH neurones, using the LHRH-secreting cell line GT1-7, showed that these cells contain transcripts encoding NRXs and one of their ligands (NRL1), at least one PCDHα (CNR-8/PCDHα10), and the CASPR1/contactin complex. The results indicate that the prepubertal female monkey hypothalamus contains a plethora of adhesion/signalling molecules with different but complementary functions, and that an LHRH neuronal cell line expresses key components of this structural complex. The presence of such cell–cell communication machinery in the neuroendocrine brain suggests an integrated participation of their individual components in the central control of female sexual development. [ABSTRACT FROM AUTHOR]

Different percutaneous interventions can be used lo treat coarctation of the aorta. However, a great amount of information is still needed regarding the long-term course. This article reviews our experience spanning 21 years in the percutaneous treatment of aortic coarctation. Four different conditions for treatment were considered. The first condition 1 (group 1) was balloon angioplasty in neonates and infants with untractable heart failure (n = 54: mean age. 1.2 ± 1.4 months). After balloon angioplasty. most infants sustained significant clinical improvement. However, 9 patients died in the hospital (17%). As a result, we monitored the course of the 45 survivors during a mean period of 10 ± 6 years (range. 1-19). During this follow-up period, 17 patients needed a single additional intervention on coarctation (8 underwent surgery and 9 were treated percutaneously). After this second treatment. 11 patients needed one or more further interventions. The actuarial survival probability was 83% at 19 years, with 43% of patients remaining surgery free and 23% reintervention free. The second condition (group 2) was balloon angioplasty in children and adults with coarctation of the aorta before the stenting era (n = 28; mean age. 13 ± 8 years). After treatment, serial hemodynamic and angiographic studies were performed. The long-term relief was higher in patients with a discrete type of coarctation. The rate of late aneurysm formation was 6%. The third condition (group 3) was stent palliation in infants and children younger than the age of 6 years (n = 17; mean age, 2.1 ± 1.7 years). The stent was implanted for nondilatable stenoses, as a nondefinitive procedure. Stent palliation provides complete initial relief in hypoplastic coarctations or life-threatening conditions. However, further stent expansion is required to ensure adequate stent diameter in the growing aortic wall. In addition, late intrastent proliferation may occur in small stent diameters (18%) and aneurysm formation in hypoplastic coarctations (18%). Both late complications can be managed percutaneously. The fourth condition (group 4) was stent repair of severe aortic coarctation in adults, adolescents, and children older than the age of 6 years (n = 73; mean age. 20 ± 12 years). Significant relief was observed after treatment, which persisted at follow-up. One patient died at treatment (1.3%). After a mean follow- up of 5 ± 3 years, all 72 patients remained symptom free and no restenosis or late ancurysm were detected. [ABSTRACT FROM AUTHOR]

By first-principles total-energy calculations, we investigated the thermodynamic stability of the MAX solid solution MoxV4-xAlC3 in the 0 ≤ x ≤ 4 range. Results evidence that lattice parameter a increases as a function of Mo content, while the c parameter reaches its maximum expansion at x = 2.5. After that, a contraction is noticed. Mo occupies VI sites randomly until the out-of-plane ordered Mo2V2AlC3 alloy is formed. We employed the Defect Formation Energy (DFE) formalism to evaluate the thermodynamic stability of the alloys. Calculations show five stable compounds. At V-rich conditions and from Mo-rich to Mo-moderated conditions, the pristine V4AlC3 MAX is stable. In the region of V-poor conditions, from Mo-rich to Mo-moderated growth conditions, the solid solutions with x = 0.5, 1, and 1.5 and the o-MAX Mo2V2AlC3 are thermodynamically stable. The line profiles of the Electron Localization Function and Bader charge analysis show that the V-C interaction is mainly ionic, while the Mo-C is covalent. Also, the exfoliation energy to obtain a MXene layer is ~ 0.4 eV/Å2. DFE also shows that MXenes exfoliated from the MAX phase with the same Mo content and atomic arrangement are thermodynamically stable. Our results get a deeper atomic scale understanding of the previously reported experimental evidence. [ABSTRACT FROM AUTHOR]