Using clinical estimate or catheter measurement of urethral mid-point result in similar retropubic mid-urethral sling position: a randomized trial.

INTRODUCTION AND HYPOTHESIS: The objective was to determine whether standardized, intraoperative urethral measurement improves retropubic mid-urethral sling (RPMUS) positioning and if the intraoperative position remains stable at 2 weeks postoperatively. METHODS: Participants undergoing a RPMUS were randomized to mid-urethral placement as per usual surgical care (no Foley catheter measurement, no-FCM) vs urethral mid-point Foley catheter measurement (FCM). The primary outcomes were RPMUS location as determined by 2D and 3D ultrasound 2 weeks postoperatively (as percentage from urethral meatus - relative to the urethral length) and intraoperatively following the RPMUS placement. RESULTS: Forty-four women enrolled, underwent RPMUS, and provided baseline data and intraoperative ultrasound measurements; of these, 36 (82%) had interpretable intraoperative and postoperative ultrasound measurements. Demographic data were similar in the two groups. The mean RPMUS mid-point was 57 % and 55 % in measured and controls (p = 0.685); this same measurement was relatively unchanged at 2 weeks postoperatively at 57% and 54% respectively (p = 0.538). Very much and much improvement was reported on the PGI-I by 84% and 85% of participants in the FCM and no-FCM groups respectively. CONCLUSIONS: Intraoperative RPMUS position at 2 weeks after surgery is similar to the intraoperative position. Compared with usual surgical care, intraoperative measurement of urethral mid-point with a Foley catheter did not affect RPMUS sling position.

The urobiome of continent adult women: a cross-sectional study.

OBJECTIVE: To characterise the bladder microbiota of continent adult women. DESIGN: Cross-sectional study of adult women who contributed catheterised urine samples, completed validated symptom questionnaires, and provided demographic data. SETTING: US academic medical centre. POPULATION: Well-characterised continent adult women. METHODS: Participants contributed symptoms questionnaires, demographic data, and catheterised urine samples that were analysed by enhanced urine culture methodology and 16S rRNA gene sequencing. MAIN OUTCOME MEASURES: Associations between demographics and microbial community state structures (urotypes, defined by the dominant taxon of each specimen). RESULTS: The bladder microbiota (urobiome) of a control group of 224 continent women were characterised, demonstrating variability in terms of urotype. The most common urotype was Lactobacillus (19%), which did not differ with any demographic. In contrast, the Gardnerella (P < 0.001) and Escherichia (P = 0.005) urotypes were more common in younger and older women, respectively. CONCLUSIONS: For urobiome research, enhanced culture methods and/or DNA sequencing are the preferred techniques for bacterial detection. The interpretation of clinical tests, such as the standard urine culture, should incorporate the knowledge that some women have Gardnerella or Escherichia urotypes without evidence of any clinical disorder. Clinical care strategies should preserve or restore the beneficial effects of the native urobiome, as disruption of that microbial community could result in unintended vulnerability to uropathogen invasion or opportunistic pathogen overgrowth. Longitudinal studies of urobiome responses to therapies should be encouraged. TWEETABLE ABSTRACT: In continent adult women bladder microbiome composition differs by age, with relevance for clinical practice.

CMAH genotyping survey for blood types A, B and C (AB) in purpose-bred cats.

In domestic cats, the AB blood group system consists of the three types A, B and C (also called AB). Mismatches can cause acute hemolytic transfusion reactions and hemolysis of the newborn (neonatal isoerythrolysis, NI). As blood types B and C are inherited recessively to A, breeders need to know the genotype to predict blood types in offspring and avoid NI. Several CMAH variants have been described as being associated with the b and ac alleles, and different genotyping schemes exist. Here, we genotyped 2145 cats with the original SNV panel, including SNVs c.142G>A and ∆-53, and our new scheme, with SNVs c.179G>T, c.268T>A and c.1322delT, to differentiate types A and B and added the SNV for the common ac (c.364C>T). Based upon the new scheme, all samples were assigned the correct genotype. No discordances appeared for the A allele, and new breed-specific SNVs (c.179G>T, c.1322delT) for the b allele were discovered. Furthermore, the genotypes A/ac (type A), ac /ac (C) and ac /b (C) could be detected. We found the variant c.179G>T in additional breeds: Ragdoll, Siberian, Scottish Fold, Chartreux, Neva Masquerade, British Shorthair and Highlander. Also, the variant c.364C>T was detected in additional breeds: Bengal, British Shorthair, Maine Coon, and Scottish Fold. We conclude that our new SNV panel is superior in genotyping cats than the original SNV panel and assures correct assignments of types A, B and C to assist veterinary clinicians and breeders to recognize, confirm and avoid blood incompatibilities such as acute hemolytic transfusion reactions and NI.

Continuous-wave modulation of a femtosecond oscillator using coherent molecules.

We describe a new method to broaden the frequency spectrum of a femtosecond oscillator in the continuous-wave (CW) domain. The method relies on modulating the femtosecond laser using four-wave mixing inside a Raman-based optical modulator. We prepare the modulator by placing deuterium molecules inside a high-finesse cavity and driving their fundamental vibrational transition using intense pump and Stokes lasers that are locked to the cavity modes. With the molecules prepared, any laser within the optical region of the spectrum can pass through the system and be modulated in a single pass. This constitutes a CW optical modulator at a frequency of 90 THz with a steady-state single-pass efficiency of ∼10-6 and transient (10 µs-time-scale) single-pass efficiency of ∼10-4. Using our modulator, we broaden the initial Ti:sapphire spectrum centered at 800 nm and produce upshifted and downshifted sidebands centered at wavelengths of 650 nm and 1.04 µm, respectively.

Development, preclinical evaluation and validation of a novel quick vascular closure device for transluminal, cardiac and radiological arterial catheterization.

Following percutaneous coronary intervention, vascular closure devices (VCDs) are increasingly used to reduce time to ambulation, enhance patient comfort, and reduce potential complications compared with traditional manual compression. Newer techniques include complicated, more or less automated suture devices, local application of pads or the use of metal clips and staples. These techniques often have the disadvantage of being time consuming, expensive or not efficient enough. The VCD failure rate in association with vascular complications of 2.0-9.5%, depending on the type of VCD, is still not acceptable. Therefore, the aim of this study is to develop a self-expanding quick vascular closure device (QVCD) made from a bioabsorbable elastic polymer that can be easily applied through the placed introducer sheath. Bioabsorbable block-co-polymers were synthesized and the chemical and mechanical degradation were determined by in vitro tests. The best fitting polymer was selected for further investigation and for microinjection moulding. After comprehensive haemocompatibility analyses in vitro, QVCDs were implanted in arterial vessels following arteriotomy for different time points in sheep to investigate the healing process. The in vivo tests proved that the new QVCD can be safely placed in the arteriotomy hole through the existing sheath instantly sealing the vessel. The degradation time of 14 days found in vitro was sufficient for vessel healing. After 4 weeks, the remaining QVCD material was covered by neointima. Overall, our experiments showed the safety and feasibility of applying this novel QVCD through an existing arterial sheath and hence encourage future work with larger calibers.

Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits.

BACKGROUND/OBJECTIVES: The forkhead factor Foxa3 is involved in the early transcriptional events controlling adipocyte differentiation and plays a critical function in fat depot expansion in response to high-fat diet regimens and during aging in mice. No studies to date have assessed the potential associations of genetic variants in FOXA3 with human metabolic outcomes. SUBJECTS/METHODS: In this study, we sequenced FOXA3 in 392 children, adolescents and young adults selected from several cohorts of subjects recruited at the National Institute of Child Health and Human Development of the National Institutes of Health based on the availability of dual-energy X-ray absorptiometry data, magnetic resonance imaging scans and DNA samples. We assessed the association between variants present in these subjects and metabolic traits and performed in vitro functional analysis of two novel FOXA3 missense mutations identified. RESULTS: Our analysis identified 14 novel variants and showed that the common single-nucleotide polymorphism (SNP) rs28666870 is significantly associated with greater body mass index, lean body mass and appendicular lean mass (P values 0.009, 0.010 and 0.013 respectively). In vitro functional studies showed increased adipogenic function for the FOXA3 missense mutations c.185C>T (p.Ser62Leu) and c.731C>T (p.Ala244Val) compared with FOXA3-WT. CONCLUSIONS: Our study identified novel FOXA3 variants and mutations, assessed the adipogenic capacity of two novel missense alterations in vitro and demonstrated for the first time the associations between FOXA3 SNP rs28666870 with metabolic phenotypes in humans.

Urethral sensation following reconstructive pelvic surgery.

INTRODUCTION AND HYPOTHESIS: Most urethral neuromuscular function data focus on efferent rather than afferent innervation. We aimed to determine if changes exist in urethral afferent nerve function before and after reconstructive pelvic surgery (RPS). Secondarily, we compared afferent urethral innervation in women with and without stress urinary incontinence undergoing RPS. METHODS: Participants underwent current perception threshold (CPT) and urethral anal reflex (UAR) testing prior to surgery and again post-operatively. Wilcoxon signed ranked test and Spearman's correlations were used and all tests were two-sided. p = 0.05 was considered to indicate statistical significance. RESULTS: Urethral CPT thresholds increased significantly after RPS, consistent with decreased urethral afferent function. Pre-operative urethral CPT thresholds at 5 and 250 Hz were lower in SUI women (10 [IQR 5-29], 40 [32-750]) compared with continent women (63 [14-99], 73 [51-109]; p = 0.45, p = 0.020), signifying increased urethral sensation or easier activation of urethral afferents in SUI women. CONCLUSIONS: Reconstructive pelvic surgery is associated with a short-term deleterious impact on urethral afferent function, as demonstrated by the higher levels of stimuli required to activate urethral afferent nerves (decreased urethral sensation) immediately after RPS. Women with SUI required lower levels of stimuli to activate urethral afferent nerves prior to RPS, although UAR latencies were similar regardless of concomitant SUI.

Using crowdsourcing to compare temporal, social temporal, and probability discounting among obese and non-obese individuals.

Previous research comparing obese and non-obese samples on the delayed discounting procedure has produced mixed results. The aim of the current study was to clarify these discrepant findings by comparing a variety of temporal discounting measures in a large sample of internet users (n=1163) obtained from a crowdsourcing service, Amazon Mechanical Turk (AMT). Measures of temporal, social-temporal (a combination of standard and social temporal), and probability discounting were obtained. Significant differences were obtained on all discounting measures except probability discounting, but the obtained effect sizes were small. These data suggest that larger-N studies will be more likely to detect differences between obese and non-obese samples, and may afford the opportunity, in future studies, to decompose a large obese sample into different subgroups to examine the effect of other relevant measures, such as the reinforcing value of food, on discounting.

Current evidence supporting obstetric fistula prevention strategies in sub Saharan Africa: a systematic review of the literature.

Obstetric fistula has been eliminated in developed countries, but remains highly prevalent in sub-Saharan Africa. The End fistula campaign is the first concerted effort to eradicate the disease. The objective of this review is to retrieve and link available evidence to obstetric fistula prevention strategies in sub-Saharan Africa, since the campaign began. We searched databases for original research on obstetric fistula prevention. Fifteen articles meeting inclusion criteria were assessed for quality, and data extraction was performed. Grey literature provided context. Evidences from the articles were linked to prevention strategies retrieved from grey literature. The strategies were classified using an innovative target-focused method. Gaps in the literature show the need for fistula prevention research to aim at systematically measuring incidence and prevalence of the disease, identify the most effective and cost-effective strategies for fistula prevention and utilise innovative tools to measure impact of strategies in order to ensure eradication of fistula.

Improving the health care of geriatric patients: management of urinary incontinence: a position paper.

A multidisciplinary German expert group met in 2012 to discuss the current status and prospects of health care of geriatric patients with urinary incontinence in Germany. The purpose of this position paper is to raise awareness among health care providers for the challenges associated with adequate management of urinary incontinence in frail elderly. The experts agree that a multidisciplinary collaboration is essential for the successful treatment of urinary incontinence symptoms which are often associated with loss of autonomy and social isolation. For most geriatric patients, usually the general practitioner is the first contact when seeking help. Hence, the general practitioner plays a crucial role in the coordination of diagnosis and treatment. The involved health care providers should have adequate education and training in their respective disciplines and should be networked allowing quick turnaround times. Non-pharmacological treatments (e.g. behavioural interventions) should have been tried before any pharmacotherapy is initiated. If pharmacological treatment of urinary incontinence involves the use of anticholinergic agents, cognitive performance should be monitored regularly. If indicated, anticholinergic agents with a documented efficacy and safety profile, explicitly assessed in the elderly population, should be preferred.

Supercooling of the A phase of 3He.

Because of the extreme purity, lack of disorder, and complex order parameter, the first-order superfluid 3He A-B transition is the leading model system for first order transitions in the early universe. Here we report on the path dependence of the supercooling of the A phase over a wide range of pressures below 29.3 bar at nearly zero magnetic field. The A phase can be cooled significantly below the thermodynamic A-B transition temperature. While the extent of supercooling is highly reproducible, it depends strongly upon the cooling trajectory: The metastability of the A phase is enhanced by transiting through regions where the A phase is more stable. We provide evidence that some of the additional supercooling is due to the elimination of B phase nucleation precursors formed upon passage through the superfluid transition. A greater understanding of the physics is essential before 3He can be exploited to model transitions in the early universe.

Crop and Non-Crop Plants as Potential Reservoir Hosts of Alfalfa mosaic virus and Cucumber mosaic virus for Spread to Commercial Snap Bean.

Diseases caused by aphid-transmitted viruses such as Alfalfa mosaic virus (AMV) and Cucumber mosaic virus (CMV) have increased in snap bean (Phaseolus vulgaris) in the Midwestern United States. Plants immediately surrounding agricultural fields may serve as primary virus inocula for aphids to acquire and transmit to bean crops. The project objectives were to (i) identify potentially important AMV and CMV reservoirs among naturally infected plants and (ii) determine the relationship between the virus inoculum potential (VIP) in adjacent crop field margins and virus incidence in P. vulgaris. From 2006 to 2008, surveys were conducted to quantify the virus incidence and percentage cover (2008 only) of plants present within 5 m of the P. vulgaris crop. In all, 4,350 individual plants representing 44 species were assayed, with overall AMV and CMV incidences averaging 12 and 1.5%, respectively. A VIP index was developed and used to rank the importance of virus-susceptible plants in adjacent field margins. The overall VIP index for AMV in field margins was weakly associated with AMV incidence in P. vulgaris and no relationship was observed between local CMV inoculum and P. vulgaris incidence, suggesting that factors additional to local inoculum sources may influence CMV epidemics in P. vulgaris.

Differentiation and reversal of malignant changes in colon cancer through PPARgamma.

PPARgamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPARgamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.

The behavioral economics and neuroeconomics of reinforcer pathologies: implications for etiology and treatment of addiction.

The current paper presents a novel approach to understanding and treating addiction. Drawing from work in behavioral economics and developments in the new field of neuroeconomics, we describe addiction as pathological patterns of responding resulting from the persistently high valuation of a reinforcer and/or an excessive preference for the immediate consumption of that reinforcer. We further suggest that, as indicated by the competing neurobehavioral decision systems theory, these patterns of pathological choice and consumption result from an imbalance between two distinct neurobehavioral systems. Specifically, pathological patterns of responding result from hyperactivity in the evolutionarily older impulsive system (which values immediate and low-cost reinforcers) and/or hypoactivity in the more recently evolved executive system (which is involved in the valuation of delayed reinforcers). This approach is then used to explain five phenomena that we believe any adequate theory of addiction must address.

Salzburg Skiing for the Elderly Study: changes in cardiovascular risk factors through skiing in the elderly.

Numerous studies have shown that treatment of the modifiable cardiovascular risk factors (CVRF) results in a decreased risk to suffer from stroke or myocardial infarction. Despite the fact that exercise training is a potent treatment choice for CVRF, this is the first randomized study to assess the effects of alpine skiing on CVRF in elderly skiers. Subjects (n=42) were randomized into an intervention group (IG; n=22; 12 males/10 females; age: 66.6 ± 2.1 years) completing 12 weeks of guided skiing or a control group (CG; n=20; 10 males/10 females; age: 67.3 ± 4.4 years). CVRF were assessed before and after the intervention period. No cardiovascular event occurred within a total of 795.1 h of skiing. A significant increase in exercise capacity in IG (ΔVO(2 max) : +2.0 mL/kg/min, P=0.005) but not in CG (ΔVO(2 max) : -0.1 mL/kg/min, P=0.858; IG vs CG: P=0.008) as well as a decrease in body fat mass [IG: -2.3%, P<0.0001; CG: ± 0.0%, P=0.866; IG vs CG: P<0.0001] was achieved. Blood pressure, blood lipids, heart rate and everyday physical activity remained essentially unchanged. Alpine skiing in the elderly is safe with respect to cardiovascular events, and improves some, but not all CVRF.

Skeletal muscle remodeling in response to alpine skiing training in older individuals.

This study investigated whether regular alpine skiing could reverse sarcopenia and muscle weakness in older individuals. Twenty-two older men and women (67 ± 2 years) underwent 12 weeks of recreational skiing, two to three times a week, each session lasting ∼ 3.5 h. An age-matched, inactive group (n=20, 67 ± 4 years) served as a control (CTRL). Before and after the training period, knee extensors muscle thickness (T(m) ), pennation angle (θ) and fascicle length (L(f) ) of the vastus lateralis muscle were measured by ultrasound. Maximum isokinetic knee extensor torque (MIT) at an angular velocity of 60°/s was measured by dynamometry. After the training, T(m) increased by 7.1% (P<0.001), L(f) by 5.4% (P<0.02) and θ by 3.4% (P<0.05). The increase in T(m) was matched by a significant gain in MIT (13.3%, P<0.001). No significant changes, except for a decrease in θ (2.1%, P<0.02), were found in the CTRL group. The gain in T(m) in the training group correlated significantly with an increase in the focal adhesion kinase content, pointing to a primary role of this mechano-sensitive protein in sarcomere remodeling with muscle hypertrophy. Overall, the results show that alpine skiing is an effective intervention for combating sarcopenia and weakness in old age.

Load-sensitive adhesion factor expression in the elderly with skiing: relation to fiber type and muscle strength.

We hypothesized that 12 weeks of downhill skiing mitigates the functional deficits of knee extensor muscles in elderly subjects due to the specific recruitment of fast motor units during forceful turns on the slope. Downhill skiing led to a 1.4-fold increase in the mean cross-sectional area of slow (P=0.04)- and fast (P=0.08)-type muscle fibers. Fold changes in the expression of the structural component of focal adhesions, gamma-vinculin, were correlated with alterations in concentric force (r=0.64). Hypertrophy of fast fibers was more pronounced in women than in men (1.7 vs 1.1). Gender-specific structural-functional adjustments of knee extensor muscles and attached patellar tendon were reflected by altered expression of pro- vs de-adhesive proteins and a number of correlations. The de-adhesive protein tenascin-C was selectively increased in women compared with men (1.7 vs 1.1) while the content of the adhesive collagen XII was specifically reduced in women. The pro-adhesive focal adhesion kinase showed a specific increase in men compared with women (1.9 vs 1.1). Our findings indicate that quantitatively matched adaptations in slow and fast motor units of extensor muscle underlie the preventive effect of skiing against sarcopenia and support that hypertrophy and reinforcement of fiber adhesion operate in the improvement of muscle strength.

NHLRC1 homozygous dodecamer expansion in a Newfoundland dog with Lafora disease.

Lafora disease is a genetic disease caused, in humans, by mutations in EPM2A and NHLRC1 genes, resulting in accumulation of polyglucosan bodies within neurons. Affected subjects present progressive neurological signs characterised primarily by myoclonic epilepsy. In dogs, Lafora disease has been described mainly in miniature wire-haired Dachshunds, where a dodecamer expansion in NHLRC1 gene has been identified. The same mutation has then been detected in the Basset Hound, Beagle, Chihuahua and Pembroke Welsh Corgi breeds. This is the first case of a Newfoundland dog with myoclonic epilepsy diagnosed with Lafora disease based on confirmed dodecamer expansion in the NHLRC1 gene. Lafora disease is being progressively recognised in different unrelated breeds suggesting a wider distribution in the canine population than previously thought.

An innovative local treatment for staphylococcal scalded skin syndrome.

Staphylococcal scalded skin syndrome (SSSS) is the clinical term used to describe a range of blistering skin disorders induced by the exfoliative toxins of Staphylococcus aureus and prevalently affects neonates, infants and toddlers who lack antibodies to S. aureus toxins. SSSS is a highly contagious disease and is characterised by erythema and fever, followed by the formation of large fragile superficial blisters, which rupture only to leave extensive areas of denuded skin. A diagnosis of SSSS relies on the clinical picture, as well as on histological and microbiological findings. Neonates and young infants are particularly susceptible to a lack of the protective skin barrier, which may cause excessive protein and fluid losses, hypothermia and secondary infection. Due to a complete denudation of skin, the patients also suffer from almost unbearable pain. In our communication, we present an innovative temporary coverage of the denuded skin with Suprathel (PolyMedics Innovations GmbH, Denkendorf, Germany). Suprathel relieves pain, prevents heat loss and secondary infection, accelerates wound healing, does not need to be changed and makes daily care easy for the nurses and is well tolerable for the patient.

Seasonal phenology of Aphis glycines (Hemiptera: Aphididae) and other aphid species in cultivated bean and noncrop habitats in Wisconsin.

The occurrence of aphid-transmitted viruses in agricultural crops of the Midwest and northeastern United States has become more frequent since the arrival and establishment of the soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae). A. glycines is a competent vector of plant viruses and may be responsible for recent virus epidemics in Wisconsin snap bean, Phaseolus vulgaris L., fields. To determine whether vegetation surrounding crop fields could serve as sources of virus inocula, we examined the settling activity ofA. glycines and other aphid species in agricultural crops and noncrop field margins adjacent to snap bean fields. Noncrop field margins were made up of numerous virus-susceptible plant species within 10 m from snap bean field edges. During summers 2006 and 2007, horizontal pan traps were placed in commercial soybean [Glycine max (L.) Merr.], snap bean, and surrounding field margins to characterize aphid flight activity patterns in the different habitat types. Alate abundance and peak occurrence across years varied between crop and noncrop field margins and differed among patches of plants in field margins. Overall aphid activity peaked late in the season (21 August in 2006 and 28 July in 2007); with the majority (52%) of total aphids trapped in all habitats being A. glycines. Susceptibility to viral infection and confirmed visitation of A. glycines to these forage plants suggests the importance ofnoncrop habitats as potential sources of primary virus inoculum. Viral disease onset followed peak aphid flights and further implicates A. glycines as a likely vector of viruses in commercial bean and other crops in Wisconsin.