Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training

Introduction: The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT. Materials and Methods: Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women. Results: Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect. Conclusions: Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management

Design of a low band gap oxide ferroelectric: Bi6_6Ti4_4O17_{17}

A strategy for obtaining low band gap oxide ferroelectrics based on charge imbalance is described and illustrated by first principles studies of the hypothetical compound Bi$_6$Ti$_4$O$_{17}$, which is an alternate stacking of the ferroelectric Bi$_4$Ti$_3$O$_{12}$. We find that this compound is ferroelectric, similar to Bi$_4$Ti$_3$O$_{12}$ although with a reduced polarization. Importantly, calculations of the electronic structure with the recently developed functional of Tran and Blaha yield a much reduced band gap of 1.83 eV for this material compared to Bi$_4$Ti$_3$O$_{12}$. Therefore, Bi$_6$Ti$_4$O$_{17}$ is predicted to be a low band gap ferroelectric material

Messy entanglements: research assemblages in heart transplantation discourses and practices

The paper engages with a variety of data around a supposedly single biomedical event, that of heart transplantation. In conventional discourse, organ transplantation constitutes an unproblematised form of spare part surgery in which failing biological components are replaced by more efficient and enduring ones, but once that simple picture is complicated by employing a radically interdisciplinary approach, any biomedical certainty is profoundly disrupted. Our aim, as a cross-sectorial partnership, has been to explore the complexities of heart transplantation by explicitly entangling research from the arts, biosciences and humanities without privileging any one discourse. It has been no easy enterprise yet it has been highly productive of new insights. We draw on our own ongoing funded research with both heart donor families and recipients to explore our different perceptions of what constitutes data and to demonstrate how the dynamic entangling of multiple data produces a constitutive assemblage of elements in which no one can claim priority. Our claim is that the use of such research assemblages and the collaborations that we bring to our project breaks through disciplinary silos to enable a fuller comprehension of the significance and experience of heart transplantation in both theory and practice

Developing Central Nervous System and Vulnerability to Platinum Compounds

Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability

Pilanesbergite: a new rock-forming mineral occurring in nepheline syenite from the Pilanesberg Alkaline Complex, South Africa

peer reviewedWe report the description and the characterization of a new mineral species, found in a rock sample from the geological formation called the Pilanesberg Complex, South Africa. This is a silicate mineral that contains a significant amount of sodium, calcium, iron, titanium and fluorine. Its atomic structure shows that it is related to other wöhlerite-group minerals. This work provides new insights into the crystallization conditions that ruled the formation of the Pilanesberg complex

Viable tax constitutions

Taxation is only sustainable if the general public complies with it. This observation is uncontroversial with tax practitioners but has been ignored by the public finance tradition, which has interpreted tax constitutions as binding contracts by which the power to tax is irretrievably conferred by individuals to government, which can then levy any tax it chooses. However, in the absence of an outside party enforcing contracts between members of a group, no arrangement within groups can be considered to be a binding contract, and therefore the power of tax must be sanctioned by individuals on an ongoing basis. In this paper we offer, for the first time, a theoretical analysis of this fundamental compliance problem associated with taxation, obtaining predictions that in some cases point to a re-interptretation of the theoretical constructions of the public finance tradition while in others call them into question

Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia

In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules

SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL