A comparison of sacral neuromodulation vs. transvaginal electrical stimulation for the treatment of refractory overactive bladder: The impact on quality of life, body image, sexual function, and emotional well-being

Overactive bladder syndrome (OAB) is defined by the presence of urinary urgency, with or without urge incontinence, usually accompanied by an increase in urinary frequency and nocturia in the absence of urinary tract infections (UTI) or other diseases. The overall prevalence of OAB symptoms in the female population is reported to be 16.6% and increases with advancing age and menopause. The aetiology of OAB is not fully understood and is likely to affect a heterogeneous population of patients due to changes to their central and peripheral nervous systems. Although OAB is frequently associated with female sexual dysfunction (FSD), its real impact on sexual function in women has been evaluated only in a few studies. The first line of treatment for OAB includes behavioural modification and physical therapy, either as monotherapies or in combination. Many patients who have not had success in managing their symptoms with more conservative therapies may decide to resort to third-line treatments for refractory OAB. These treatments include neuromodulation therapies, particularly transvaginal electrical stimulation (TES) and sacral neuromodulation (SN). The aim of this short commentary is to provide an overview of the effectiveness of these treatments and of their impact on quality of life, body image, sexual function, and emotional well-being

An update on treatment options for interstitial cystitis

Interstitial cystitis or bladder pain syndrome (IC/BPS) is a chronic pelvic pain syndrome related to the urinary bladder. The ideal treatment should match as much as possible with the pathophysiologic causes of the IC/BPS, but the scarcely available evidence limits this approach, with the majority of available treatments that are primarily targeted to the control of symptoms. The treatment strategies have traditionally focused on the bladder, which is considered the primary end-organ and source of pain. Nevertheless, the growing body of evidence suggests a multifaceted nature of the disease with systemic components. In general, guidelines recommend the personalized and progressive approach, that starts from the more conservative options and then advances toward more invasive and combined treatments. The behavioral changes represent the first and most conservative steps. They can be combined with oral medications or progressively with intravesical instillation of drugs, up to more invasive techniques in a combined way. Despite the multiple available options, the optimal treatment is not easy to be found. Only further investigation on the etiopathogenetic mechanisms, taking into account the differences among subgroups, and the interaction between central and peripherical factors may allow providing a real improvement in the treatment and management of these patients

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

What’s really damaging the Reef?: Tracing the origin and fate of the ecologically detrimental sediment and associated bioavailable nutrients

This report addresses six key systematic questions to help inform the debate on the influence of anthropogenic sediment and associated particulate nutrients delivered to the Great Barrier Reef (GBR) lagoon. They are: 1. What is the influence of the newly-delivered sediment (i.e. from flood plumes) on turbidity regimes at coral reef and seagrass locations of the inshore GBR? 2. What is the contribution of the anthropogenic component of this sediment on turbidity regimes? 3. What are the characteristics of the suspended particulate matter (and associated particulate nutrients) that influence light and turbidity regimes and how do these change over the estuarine mixing gradient of flood plumes? 4. How does the particulate organic component of the suspended particulate matter and associated microbial community composition change from the catchment to reef? 5. How bioavailable is the suspended particulate matter along the estuarine mixing gradient 6. Where does the sediment (and associated particulate nutrients) that influence light and turbidity regimes in the GBR come from in the Burdekin catchment so that management efforts can be prioritised? This final project report is divided into eight separate stand-alone research chapters which collectively address these six key questions

Use of camera trapping in determining Iberian lynx population parameters: The use area and its limitations

Below are the results of the survey of the Iberian lynx obtained with camera-trapping between 2000 and 2007 in Sierra Morena. Two very important aspects of camera-trapping concerning its efficiency are also analyzed. The first is the evolution along years according to the camera-trapping type used of two efficiency indicators. The results obtained demonstrate that the most efficient lure is rabbit, though it is the less proven (92 trap-nights), followed by camera-trapping in the most frequent marking places (latrines). And, we propose as a novel the concept of use area as a spatial reference unit for the camera-trapping monitoring of non radio-marked animals is proposed, and its validity discussed

Film Edge Nonlocal Spin Valves

Spintronics is a new paradigm for integrated digital electronics. Recently established as a niche for nonvolatile magnetic random access memory (MRAM), it offers new functionality while demonstrating low power and high speed performance. However, to reach high density spintronic technology must make a transition to the nanometer scale. Prototype devices are presently made using a planar geometry and have an area determined by the lithographic feature size, currently about 100 nm. Here we present a new nonplanar geometry in which one lateral dimension is given by a film thickness, the order of 10 nm. With this new approach, cell sizes can shrink by an order of magnitude. The geometry is demonstrated with a nonlocal spin valve, where we study devices with an injector/detector separation much less than the spin diffusion length.Comment: 10 pages, 3 figure

Sediment tracing from the catchment to reef 2016 to 2018: Flood plume, marine sediment trap and logger data time series

The sediment dynamics at marine sites in the inshore GBRL region likely fall into three separate categories including sites where: 1. input of new terrigenous sediments have by far the greatest influence on sediment exposure and subsequent resuspension (e.g. Dunk Island, Orpheus Island, Havannah Island, Cleveland Bay?); 2. input of new terrigenous sediments are at least equivalent to resuspension events which likely increases upon larger river discharge events (e.g. Cleveland Bay?, Orchard Rocks). 3. input of new terrigenous sediments are less than or equal to common resuspension events (e.g. Middle Reef, Geoffrey Bay). This provides some of the first empirical data to support the findings of the satellite photic depth modelling of Fabricius et al. (2014, 2016) where the delivery of new terrigenous sediment considerably influences water clarity on the inshore Great Barrier Reef

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged \u3e/=60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P \u3c 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P \u3c 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P \u3c 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival

A major star formation region in the receding tip of the stellar Galactic bar

We present an analysis of the optical spectroscopy of 58 stars in the Galactic plane at $l=27$\arcdeg, where a prominent excess in the flux distribution and star counts have been observed in several spectral regions, in particular in the Two Micron Galactic Survey (TMGS) catalog. The sources were selected from the TMGS, to have a $K$ magnitude brighter than +5 mag and be within 2 degrees of the Galactic plane. More than 60% of the spectra correspond to stars of luminosity class I, and a significant proportion of the remainder are very late giants which would also be fast evolving. This very high concentration of young sources points to the existence of a major star formation region in the Galactic plane, located just inside the assumed origin of the Scutum spiral arm. Such regions can form due to the concentrations of shocked gas where a galactic bar meets a spiral arm, as is observed at the ends of the bars of face-on external galaxies. Thus, the presence of a massive star formation region is very strong supporting evidence for the presence of a bar in our Galaxy.Comment: 13 pages (latex) + 4 figures (eps), accepted in ApJ Let

Lysogenization of a lactococcal host with three distinct temperate phages provides homologous and heterologous phage resistance

Lactococcus lactis is the most widely exploited microorganism in global dairy fermentations. Lactococcal strains are described as typically harboring a number of prophages in their chromosomes. The presence of such prophages may provide both advantages and disadvantages to the carrying host. Here, we describe the deliberate generation of three distinct lysogens of the model lactococcal strain 3107 and the impact of additional prophage carriage on phage-resistance and anti-microbial susceptibility. Lysogen-specific responses were observed, highlighting the unique relationship and impact of each lysogenic phage on its host. Both homologous and heterologous phage-resistance profiles were observed, highlighting the presence of possible prophage-encoded phage-resistance factors. Superinfection exclusion was among the most notable causes of heterologous phage-resistance profiles with resistance observed against members of the Skunavirus, P335, P087, and 949 lactococcal phage groups. Through these analyses, it is now possible to identify phages that may pursue similar DNA injection pathways. The generated lysogenic strains exhibited increased sensitivity to the antimicrobial compounds, nisin and lysozyme, relative to the parent strain, although it is noteworthy that the degree of sensitivity was specific to the individual (pro)phages. Overall, the findings highlight the unique impact of each prophage on a given strain and the requirement for strain-level analysis when considering the implications of lysogeny