The decline in available oestrogen after menopause is a possible etiological factor in pelvic floor disorders like vaginal atrophy (VA), urinary incontinence (UI), overactive bladder (OAB) and pelvic ...organ prolapse (POP). This systematic review will examine the evidence for local oestrogen therapy in the treatment of these pelvic floor disorders.
We performed a systematic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the non-MEDLINE subset of PubMed from inception to May 2014. We searched for local oestrogens and VA (I), UI/OAB (II) and POP (III). Part I was combined with broad methodological filters for randomized controlled trials (RCTs) and secondary evidence. For part I and II two reviewers independently selected RCTs evaluating the effect of topical oestrogens on symptoms and signs of VA and UI/OAB. In part III all studies of topical oestrogen therapy in the treatment of POP were selected. Data extraction and the assessment of risk of bias using the Cochrane Risk of Bias Tool was undertaken independently by two reviewers.
The included studies varied in ways of topical application, types of oestrogen, dosage and treatment durations. Objective and subjective outcomes were assessed by a variety of measures. Overall, subjective and urodynamic outcomes, vaginal maturation and vaginal pH changed in favor of vaginal oestrogens compared to placebo. No obvious differences between different application methods were revealed. Low doses already seemed to have a beneficial effect. Studies evaluating the effect of topical oestrogen in women with POP are scarce and mainly assessed symptoms and signs associated with VA instead of POP symptoms.
Topical oestrogen administration is effective for the treatment of VA and seems to decrease complaints of OAB and UI. The potential for local oestrogens in the prevention as well as treatment of POP needs further research.
Rapidly changing light conditions can reduce carbon gain and productivity in field crops because photosynthetic responses to light fluctuations are not instantaneous. Plant responses to fluctuating ...light occur across levels of organizational complexity from entire canopies to the biochemistry of a single reaction and across orders of magnitude of time. Although light availability and variation at the top of the canopy are largely dependent on the solar angle and degree of cloudiness, lower crop canopies rely more heavily on light in the form of sunflecks, the quantity of which depends mostly on canopy structure but also may be affected by wind. The ability of leaf photosynthesis to respond rapidly to these variations in light intensity is restricted by the relatively slow opening/closing of stomata, activation/deactivation of C₃ cycle enzymes, and up-regulation/down-regulation of photoprotective processes. The metabolic complexity of C₄ photosynthesis creates the apparently contradictory possibilities that C₄ photosynthesis may be both more and less resilient than C₃ to dynamic light regimes, depending on the frequency at which these light fluctuations occur. We review the current understanding of the underlying mechanisms of these limitations to photosynthesis in fluctuating light that have shown promise in improving the response times of photosynthesis-related processes to changes in light intensity.
Metabolomic and lipidomic studies measure and discover metabolic and lipid profiles in biological samples, enabling a better understanding of the metabolism of specific biological phenotypes. ...Accurate biological interpretations require high analytical reproducibility and sensitivity, and standardized and transparent data processing. Here we describe a complete workflow for nanoelectrospray ionization (nESI) direct-infusion mass spectrometry (DIMS) metabolomics and lipidomics. After metabolite and lipid extraction from tissues and biofluids, samples are directly infused into a high-resolution mass spectrometer (e.g., Orbitrap) using a chip-based nESI sample delivery system. nESI functions to minimize ionization suppression or enhancement effects as compared with standard electrospray ionization (ESI). Our analytical technique-named spectral stitching-measures data as several overlapping mass-to-charge (m/z) windows that are subsequently 'stitched' together, creating a complete mass spectrum. This considerably increases the dynamic range and detection sensitivity-about a fivefold increase in peak detection-as compared with the collection of DIMS data as a single wide mass-to-charge (m/z ratio) window. Data processing, statistical analysis and metabolite annotation are executed as a workflow within the user-friendly, transparent and freely available Galaxy platform (galaxyproject.org). Generated data have high mass accuracy that enables molecular formulae peak annotations. The workflow is compatible with any sample-extraction method; in this protocol, the examples are extracted using a biphasic method, with methanol, chloroform and water as the solvents. The complete workflow is reproducible, rapid and automated, which enables cost-effective analysis of >10,000 samples per year, making it ideal for high-throughput metabolomics and lipidomics screening-e.g., for clinical phenotyping, drug screening and toxicity testing.
Photorespiration is frequently considered a wasteful and inefficient process. However, mutant analysis demonstrated that photorespiration is essential for recycling of 2-phosphoglycolate in C₃ and C₄ ...land plants, in algae, and even in cyanobacteria operating carboxysome-based carbon (C) concentrating mechanisms. Photorespiration links photosynthetic C assimilation with other metabolic processes, such as nitrogen and sulfur assimilation, as well as C₁ metabolism, and it may contribute to balancing the redox poise between chloroplasts, peroxisomes, mitochondria and cytoplasm. The high degree of metabolic interdependencies and the pleiotropic phenotypes of photorespiratory mutants impedes the distinction between core and accessory functions. Newly developed synthetic bypasses of photorespiration, beyond holding potential for significant yield increases in C₃ crops, will enable us to differentiate between essential and accessory functions of photorespiration.
Thuillier
et al.
(
Solar Phys.
,
2015
, DOI:10.1007/s11207-015-0704-1) discuss the apparent discrepancy between the ATLAS-3 composite solar spectral irradiances (SSI) covering the ...ultraviolet/visible/near-infrared (NIR) spectral region with more recent SSI measurements in the NIR. Recent measurements from IRSPERAD, CAVIAR, SCIAMACHY, SOLSPEC/ISS (the SOLAR2 spectrum from 2008), and unadjusted SIM show that above about 1600 nm, SSI is lower by about 8 % with respect to ATLAS-3. A new correction is presented in Thuillier
et al.
(
2015
) that leads to SOLSPEC/ISS (SOLAR2rev) which is in better agreement with ATLAS-3. SOLSPEC/ISS SSI underwent a +10 % change from 2008 to 2010, leading to better agreement with ATLAS-3, but it remains unclear which year provided the proper radiometric level, 2008 (SOLAR2) or 2010 (SOLAR2rev) as no link to pre-launch calibration is established. Before interpreting the NIR SSI observations using our current physical understanding (constraints by the total solar irradiance and solar models), the cause for the discrepancy between the early ATLAS-3 and all recent measurements (without a-posteriori adjustments) needs to be understood considering instrument and calibration performance alone.
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) ...conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.
Density functional theory (DFT) is widely applied in calculations of molecules and materials. Yet, it suffers from a well-known over-emphasis on charge delocalization arising from self-interaction ...error that destabilizes localized states. Here, using the symmetric diamine N,N'-dimethylpiperazine as a model, we have experimentally determined the relative energy of a state with positive charge localized on one of the two nitrogen atoms, and a state with positive charge delocalized over both nitrogen atoms. The charge-localized state was found to be 0.33 (0.04) eV higher in energy than the charge-delocalized state. This provides an important test of theoretical approaches to electronic structure calculations. Calculations with all DFT functionals commonly used today, including hybrid functionals with exact exchange, fail to predict a stable charge-localized state. However, the application of an explicit self-interaction correction to a semi-local functional identifies both states and gives relative energy in excellent agreement with both experiment and CCSD(T) calculations.
We integrate a long-lived memory qubit into a mixed-species trapped-ion quantum network node. Ion-photon entanglement first generated with a network qubit in ^{88}Sr^{+} is transferred to ^{43}Ca^{+} ...with 0.977(7) fidelity, and mapped to a robust memory qubit. We then entangle the network qubit with a second photon, without affecting the memory qubit. We perform quantum state tomography to show that the fidelity of ion-photon entanglement decays ∼70 times slower on the memory qubit. Dynamical decoupling further extends the storage duration; we measure an ion-photon entanglement fidelity of 0.81(4) after 10 s.
Abstract An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic ...cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging computed tomography (CT) or magnetic resonance imaging (MRI), but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions.
Pseudolesions of joints are known as focal irregularities of chondral or subchondral bone in typical joint areas and occur frequent but without clinical relevance. This study aims to report the ...prevalence and describe MRI findings of a previously unreported chondral, mostly posterior located pseudolesion of the distal tibia, and to define criteria to distinguish it from pathologic osteochondral lesions, as well as from another known pseudolesion of this area - the so called “Notch of Harty”.
A tri-centric retrospective case-control study included a total of 2,428 patients with ankle MRI examinations performed over a period of 6 years. MRI scans were evaluated by three radiologists in consensus for any cartilage irregularity of the distal tibial articular surface. For this purpose, the tibial articular surface was divided into 9 topographic regions. Proton-density weighted, fat-suppressed sequences in sagittal and coronal acquisition were used to assess the postero-medial articular surface of the tibia.
Imaging features such as size and localization of cartilage irregularity and/or a cortical mould as well as presence of associated edema and/or subchondral cysts were reported. Demographic data (sex, age, and weight) was also recorded. Clinical data comprised presence of pain, movement impairment, and concomitant pathologies.
A total of 68 patients (34 male, 34 female) with a lesion of the distal tibia were identified that had a new pseudolesion (prevalence of 3%). These lesions occurred most frequently (50 out of 68, 74%) in the postero-medial distal tibia plafond and were more commonly detected in the age group of 9–30 years (47%).
In 13 of these 68 cases, the cartilage irregularity was the sole lesion without subchondral abnormalities. By defining these cases as definite pseudolesions, the prevalence was 1% and their age distribution was similar to that of the 55 other lesions with subchondral changes.
Here with 11 of the 13 cases the majority (85%) were seen in the posterior part, especially in the postero-medial part (55%) of the distal tibia. The size of the cartilage defect ranged from 1 to 7 mm, and the majority (69%) sized from 2 to 3 mm.
In 36 of 68 patients, we have seen subchondral alterations such as edema and/or cysts in addition to cartilage irregularity. 66% (n = 45) of these changes were edema and 37% (n = 25) were cysts.
None of these 68 new pseudolesions with or without subchondral changes needed surgical or arthroscopic intervention. In the radiological and orthopaedic reports, clinical symptoms such as pain or instability were never associated with our observed lesions and there was no significant correlation between the presence of motion-related pain and imaging findings of cartilage irregularity, subchondral edema, and subchondral cysts. Thirteen patients had MRI follow-up examinations. Here the lesions did not show any MR morphological changes or clinical deterioration.
Besides the new pseudolesion, which occured mainly in the posterior part of the tibia surface, we observed the “Notch of Harty” with a higher prevalence (25%) in our patient cohort. The typical localization was in the antero-medial tibial articular surface, without any edema or cysts. There were no coincidences of patients with both a new pseudolesion and the “Notch of Harty”
A new pseudolesion is typically seen in the postero-central and postero-medial tibial articular surface with a prevalence of 3% and may be associated with only a small cartilage irregularity. In many cases, however, additional findings such as bone edema and/or an adjacent bone cysts were found, which impairs differentiation of these lesions from pathologic osteochondral lesions. The latter are obviously often associated with a larger cartilage defect and clinical symptoms. Due to the balanced age distribution between those pseudolesions with and without subchondral changes and the lack of clinical symptoms, we conclude that the here reported pseudolesions are not a predilection for a clinically manifest osteochondral lesion (OCL). At the very least, the apparent lack of clinical relevance increases the likelihood that we are dealing with a new true pseudolesion.
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