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Purpose: This systematic review and dose–response meta-analysis aimed to investigate the relationship between hospital volume and outcomes for total knee arthroplasty (TKA). Methods: MEDLINE, Embase, CENTRAL and CINAHL were searched up to February 2020 for randomised controlled trials and cohort studies that reported TKA performed in hospitals with at least two different volumes and any associated patient-relevant outcomes. The adjusted effect estimates (odds ratios, OR) were pooled using a random-effects, linear dose–response meta-analysis. Heterogeneity was quantified using the I2-statistic. ROBINS-I and the GRADE approach were used to assess the risk of bias and the confidence in the cumulative evidence, respectively. Results: A total of 68 cohort studies with data from 1985 to 2018 were included. The risk of bias for all outcomes ranged from moderate to critical. Higher hospital volume may be associated with a lower rate of early revision ≤ 12 months (narrative synthesis of k = 7 studies, n = 301,378 patients) and is likely associated with lower mortality ≤ 3 months (OR = 0.91 per additional 50 TKAs/year, 95% confidence interval [0.87–0.95], k = 9, n = 2,638,996, I2 = 51%) and readmissions ≤ 3 months (OR = 0.98 [0.97–0.99], k = 3, n = 830,381, I2 = 44%). Hospital volume may not be associated with the rates of deep infections within 1–4 years, late revision (1–10 years) or adverse events ≤ 3 months. The confidence in the cumulative evidence was moderate for mortality and readmission rates; low for early revision rates; and very low for deep infection, late revision and adverse event rates. Conclusion: An inverse volume–outcome relationship probably exists for some TKA outcomes, including mortality and readmissions, and may exist for early revisions. Small reductions in unfavourable outcomes may be clinically relevant at the population level, supporting centralisation of TKA to high-volume hospitals. Level of evidence: III. Registration number: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019131209 available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=131209). [ABSTRACT FROM AUTHOR]

Rationale: It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. Objectives: The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Methods: Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). Results: L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively). Conclusions: The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD. [ABSTRACT FROM AUTHOR]

The results of a series of penetration experiments with cylindrical projectiles (diameter: 30 mm, length: 158 mm) of different tip geometries (hemispherical, conic and flat) impacting with approx. 380 m/s on cylindrical sand targets (diameter: 250 mm, length: 1 m) are presented. The projectiles are instrumented with an on-board data recorder system with acceleration sensor (G-Rec), allowing for in-situ measurement of the decelerations experienced during the impact and during the subsequent penetration process. During and after the acceleration stage inside the gun barrel, the velocities derived from the G-Rec data show a very good agreement with an independent reference velocity measurement obtained by a light barrier system. Immediately after the initial impact on the granular material (compacted sand for this study), the sensor signals indicate very strong amplitude oscillating decelerations in the range of 50,000 to 80,000 g. The measured penetration depth varied widely for identical conditions of projectile impact, using identical preparation procedures for the sand sample. Variables considered for the experimental program included projectile tip shape, initial sand compaction state, and projectile velocity. A data reduction procedure to obtain velocity and position information of the projectile while penetrating the sand assembly is presented, taking into account a constant value (offset) observed in the raw signals of G-Rec at the end of penetration process. The formation of a false tip of agglomerated quartz powder in front of the projectile was observed in all cases. The observed shape of the false tip (penetrator tip with comminuted sand) was found to be identical for all projectile tip shapes (flat, hemispherical, and conical) considered in this study. Initial examination results of the false tip using X-ray computed tomography are presented. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to demonstrate the safety and the efficacy of the self-gripping Parietex ProGrip™ mesh (Sofradim Production, Trévoux, France) used with the laparoscopic approach for inguinal hernia repair. The incidence of chronic pain, post-operative complications, patient satisfaction and hernia recurrence at follow-up after 12 months was evaluated.Methods: Data were collected retrospectively from patient files and were analyzed for 169 male and female patients with 220 primary inguinal hernias. All patients included had undergone surgical repair for inguinal hernia by the laparoscopic transabdominal preperitoneal approach using Parietex ProGrip™ meshes performed in the same clinical center in Germany. Pre-, per- and post-operative data were collected, and a follow-up after 12 months was performed prospectively. Complications, pain scored on a 0-10 numeric rating scale (NRS), patient satisfaction and hernia recurrence were assessed.Results: The only complications were minor and were post-operative: hematoma/seroma (3 cases), secondary hemorrhage through the trocar's site (2 cases), hematuria, emphysema in the inguinal regions (both sides) and swelling above the genital organs (1 case for each). At mean follow-up at 22.8 months, there were only 3 reports of hernia recurrence: 1.4 % of the hernias. Most patients (95.9 %) were satisfied or very satisfied with their hernia repair with only 1.2 % reporting severe pain (NRS score 7-10) and 3.6 % reported mild pain.Conclusion: This study demonstrates that in experienced hands, inguinal hernia repair surgery performed by laparoscopic transabdominal preperitoneal hernioplasty using Parietex ProGrip™ self-gripping meshes is rapid, efficient and safe with low pain and low hernia recurrence rate. [ABSTRACT FROM AUTHOR]

Gastrointestinal complications are frequent after allogeneic stem cell transplantation (allo-SCT). Main differential diagnoses are graft-versus-host disease (GvHD) and viral infections. In this retrospective analysis, we included 50 patients with severe vomiting or diarrhea in the first year after allo-SCT. One hundred two biopsies obtained by colonoscopy or endoscopy of the upper gastrointestinal tract were analysed by conventional histology for signs of GvHD and by qualitative polymerase chain reaction (PCR) for viral DNA of human herpesvirus 6 (HHV-6) and other virus of the herpes family. DNA of HHV-6 was detected in 38 of 75 initial samples (51%) and in 19 of 27 follow-up biopsies (70%). In the initial samples ( n = 75), HHV-6 DNA was detected in 20/37 (54%) biopsies in the presence of GvHD compared to 18/38 (47%) biopsies without signs of GvHD. At the time of the first endoscopic investigation, most patients received antiviral prophylaxis with aciclovir. None of the follow-up biopsies was HHV-6 DNA negative after antiviral treatment with aciclovir, foscarnet or ganciclovir. By univariate analysis, no risk factor for HHV-6 detection could be demonstrated. In this cohort of patients with severe gastrointestinal complications, there was no significant difference in the overall survival between patients with or without HHV-6 DNA detection in the gastrointestinal tract. In summary, the detection of HHV-6 DNA had no impact on overall survival. Moreover, antiviral therapy against HHV-6 was without effect. Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT. [ABSTRACT FROM AUTHOR]

One- and few-electron ions traditionally serve as an important testing ground for fundamental atomic structure theories and for the effects of QED, relativity and electron correlation. In the domain of high nuclear charges, new opportunities open up for precise testing and consolidating of the present understanding of the atomic structure in the regime of extreme electromagnetic fields. In this review, the current progress in experimental investigations of the heaviest H- and He-like systems at GSI Darmstadt is presented together with the planned future developments. [ABSTRACT FROM AUTHOR]

Objectives: We report the 3-year clinical experience of a large new Danish PET/CT centre without capacity limitations in relation to national and European developments.Methods: The use of PET/CT in cancer was registered from early 2006 to early 2009 to judge the impact on patient management and to compare it with national and European trends.Results: 6056 PET/CT examinations were performed in 4327 patients. Activity increased by 86 examinations per month compared with the same month the year before. Referrals came primarily from oncology (23.0%), haematology (21.6%), surgery (12.6%), internal medicine (12.7%) and gynaecology (5.5%). Referral indications were diagnosis (31.3%), staging (22.3%), recurrence detection (21.2%), response evaluation (17.0%) and other (8.2%). Response from nearly 60% of users showed that PET/CT caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. During the study period, there was a steep increase in the national use of FDG and in the European use of PET/CT.Conclusions: We recorded a constantly increasing use of PET/CT that caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. In line with national and European trends this may suggest a shift in favour of functional rather than anatomical imaging. [ABSTRACT FROM AUTHOR]

The two-photon decay of the 2 S state to the ground state in dressed atoms and one- or two-electron ions has been studied for several decades. Relativistic calculations have shown an Z-dependence of the spectral shape of this two-photon transition in one- or two-electron ions. We have measured the spectral distribution of the 1 s2 s $^1\!S_0$ → 1 s $^1\!S_0$ two-photon transition in He-like tin at the ESR storage ring using a new approach for such experiments. In this method, relativistic collisions of initially Li-like projectiles with a gaseous target were used to populate exclusively the first excited state, 1 s2 s, of He-like tin, which provided a clean two-photon spectrum. The measured two-photon spectral distribution was compared with fully relativistic calculations. The obtained results show very good agreement with the calculations for He-like tin. [ABSTRACT FROM AUTHOR]

The orientational dynamics of rod-like particles with permanent (electric or magnetic) dipole moments in a plane Couette shear flow is investigated using mesoscopic relaxation equations combined with a generalized Landau free energy. The free energy contribution due to the coupling between average alignment and dipole orientation is derived on a microscopic basis. Numerical results of the resulting eight-dimensional dynamical system are presented for the case of longitudinal dipoles and thermodynamic conditions where the equilibrium state is a (polar or non-polar) nematic. Solution diagrams reveal presence of a large variety of periodic, transient chaotic, and chaotic dynamic states of the average alignment and dipole moment, respectively, appearing as a function of Deborah number and tumbling parameter. Compared to rods without dipoles we observe a significant preference of out-of-plane kayaking-tumbling states and, generally, a higher sensitivity to the initial conditions including bistability. We also demonstrate that the average (electric) dipole moment characterizing most of the observed states yields electrodynamic (magnetic) fields of measurable strength. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) infect keratinocytes of skin and mucosa. Persistent infection can lead to the formation of benign tumors. In cases of high-risk HPV, such as HPV16 or 18, these may further progress to cancer. In order to support viral replication in suprabasal keratinocytes, the HPV E7 protein employs various strategies to keep keratinocytes in cycle and counteracts anti-proliferative signals from outside. HPV16 E7 can directly interfere with transforming growth factor-β (TGF-β) signalling by binding to Smad proteins mediating growth arrest. It has been speculated that this property of HPV16 E7 contributes to HPV-associated carcinogenesis. Here, we show that E7 proteins from different low- and high-risk HPV types bind to Smad 1 to 4. The E7 protein from HPV1, a low-risk HPV causing plantar warts, efficiently inhibited Smad 3-induced transcription. Our data strongly indicate that the Smad-binding capacity of E7 proteins from different HPVs may preserve keratinocyte proliferation required for the productive viral life cycle rather than promoting carcinogenesis. [ABSTRACT FROM AUTHOR]

Leukemic cell growth in SCID mice has been reported as a predictor of disease relapse. However, there is a paucity of literature regarding xenograft growth and clinical outcomes in non-small cell lung cancer (NSCLC). Seventy-nine specimens from patients with NSCLC were either subcutaneously implanted into SCID mice and/or placed in tissue culture. Retrospective chart review was correlated with stage, histology, necrosis, disease-free interval, and survival. Tumor xenografts were successfully established with 17 of 37 (46%) tumor biopsy tissues. Thirteen of 59 (22%) specimens grew in cell culture. Patients whose tumors grew in SCID mice had no difference in survival compared to those with no growth (n=20, p=0.42). Median survival was 36 months in 13 patients whose tumors grew in cell culture compared to 39 months in 46 patients without growth. Eight of 12 (67%) patients with metastasis showed SCID/human xenograft growth, whereas nine of 25 (36%) without metastases did so (p=0.08). Growth of tumor cells in vitro occurred in 11 of 31 (35%) adenocarcinomas, one of 25 (4%) squamous cell carcinomas, and one of three (33%) large cell carcinomas (p=0.02). Well or moderately differentiated tumors grew in cell culture in only two of 22 (9%), whereas poorly or undifferentiated tumors grew in 11 of 32 (34%) cases (p=0.03). We conclude that neither the ability of a tumor to engraft and grow in SCID mice nor its ability to grow in vitro in cell culture is a reliable predictor of disease outcome or survival in patients with NSCLC. The ability to propagate tumors in vitro appears to be more dependent upon the histological type of tumor and its degree of differentiation. [ABSTRACT FROM AUTHOR]

The structure of a fluid as described by the pair-correlation function or by the static structure factor is modified by a viscous flow. This modification already exists in the linear flow regime (Newtonian behavior) but it becomes more pronounced at higher shear rates where non-Newtonian effects, such as a dependence of the viscosity on the shear rate and normal stress differences, prevail. Examples are presented for fluids composed of spherical particles, in particular, "simple fluids" and dense colloidal dispersions, and for "complex fluids" composed of nonspherical particles and polymeric chain molecules. Calculations based on kinetic equations for the pair-correlation function or for the orientational distribution function are compared with results obtained by nonequilibrium molecular dynamics (NEMD) computer simulations, as well as with rheological and neutron scattering experiments. [ABSTRACT FROM AUTHOR]

In this work we study the stability of similarity judgements of sentences in regard to the presentation order of stimuli through MINISSA (Michigan-Israel-Nijmegen Integrated Smallest Space Analysis), which allows a Multidimensional Scaling with a triangular matrix of global similarity indices. Two forms of the same questionnaire by inverting the order of presentation of all possible unidirectional comparisons were applied. Results indicate that both forms are equivalent with similar structures and a high correlation coefficient between the judgements. We conclude a high stability of the used procedure. Furthermore, in comparison with a previous study, it could be shown that the stability of solutions obtained by MINISSA is equivalent to that obtained by INDSCAL (INdividual Differences SCALing) which is not able to handle so many data as MINISSA. [ABSTRACT FROM AUTHOR]

Objective: Besides interleukin (IL)-10, accumulating evidence from in vitro studies has indicated a strong antiinflammatory capacity for IL-13. A prospective clinical study was undertaken to assess the influence of additional brain injury on systemic IL-10 and IL-13 levels as markers for the antiinflammatory state in trauma patients.¶ Material and methods: The course of IL-10 and IL-13 plasma levels from 32 patients with an isolated severe head trauma (SHT), 50 patients with multiple injuries and additional SHT and 39 patients with multiple injuries without SHT was detected using ELISA-technique. Blood samples from 37 healthy blood donors were analysed for control.¶ Results: IL-10 levels were significantly elevated in all 3 injury groups within 3 h after trauma. The lowest initial release was detected in patients with an isolated SHT (Injury severity score; ISS: 18.1 ± 5.6). No difference could be demonstrated for the IL-10 levels from multiple injured patients with (ISS: 35.3 ± 9.6) or without additional SHT (ISS: 25.5 ± 11.7), though there were relevant differences in the ISS. In contrast, the IL-13 plasma levels were not elevated systemically after trauma.¶ Conclusions: IL-10 but not IL-13 is a detectable antiinflammatory marker in trauma patients with or without brain injury and to a minor degree in patients with an isolated SHT.¶ [ABSTRACT FROM AUTHOR]

Abstract. Polarization-resolved femtosecond experiments are shown to yield valuable insight into transition-state dynamics associated with ultra-fast photodissociation reactions of triatomic species in liquid solution. After the fundamental act of bond fission is completed, such experiments reveal rotational dynamics of the fragments, which can be used to extract information regarding fragment rotational excitation in the asymptotic limit of the reaction. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the prevalence of overweight and obesity in Swiss children and to obtain information on weight perceptions and weight control practices in this population.Design: Cross-sectional, three-stage, probability-proportionate-to-size cluster sampling.Setting: Middle schools throughout Switzerland.Subjects: A representative national sample of 595 6-12 y-old schoolchildren.Intervention: Measurement of weight and height; interview on weight perceptions and weight control practices.Results: Body mass index (BMI) was calculated and used as an indicator of overweight. The BMIs of the Swiss children were compared with US, UK, French and Swiss reference data. Depending on which reference data were used, the prevalence of obesity varied between 9.7 and 16.1% and the prevalence of overweight varied between 21.7 and 34.2%. Girls were significantly more likely to consider themselves too fat (26% and 15%, respectively) and to report currently trying to lose weight (30% and 18%, respectively) compared to boys (P<0.05).Conclusions: The prevalence of overweight in Swiss children, and its attendant health and social consequences, are important public health concerns.Sponsorship: The Swiss Foundation for Nutrition Research, Zürich, Switzerland. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the habitual salt intake of individuals living in the Côte d'Ivoire, and to monitor the iodine nutrition of adults, schoolchildren and pregnant women one year after implementation of a universal salt iodisation programme.Design: A three day weighed food records with estimation of food intake from a shared bowl based on changes on body weight, determination of sodium and iodine concentrations in 24 h (24 h) urine samples from adults, and determination of urinary iodine in spot urines from schoolchildren and pregnant women.Setting: A large coastal city (Abidjan) and a cluster of inland villages in the northern savannah region of the Côte d'Ivoire.Subjects: For the food records: 188 subjects (children and adults) in the northern villages; for the 24 h urine collections: 52 adults in Abidjan and 51 adults in the northern villages; for the spot urine collections: 110 children and 72 pregnant women in Abidjan and 104 children and 66 pregnant women in the north.Main Results: From the food survey data in the north, the total mean salt intake (s.d.) of all age groups and the adults was estimated to be 5.7 g/d (+/- 3.0), and 6.8 g/d (+/- 3.2), respectively. In the 24 h urine samples from adults, the mean sodium excretion was 2.9 g/d (+/- 1.9) in the north and 3.0 g/d (+/- 1.3) in Abidjan, corresponding to an intake of 7.3-7.5 g/d of sodium chloride. In the north the median 24 h urinary iodine excretion in adults was 163 microg/d, and the median urinary iodine in spot urines from children and pregnant women was 263 microg/l and 133 microg/l, respectively. In contrast, in Abidjan the median 24 h urinary iodine was 442 microg/d, with 40% of the subjects excreting > 500 microg/d, and the median urinary iodine in spot urines from children and pregnant women was 488 microg/l and 364 microg/l, respectively. Nearly half of the children in Abidjan and 32% of the pregnant women were excreting > 500 microg/l.Conclusion: Based on the estimates of salt intake in this study, an optimal iodine level for salt (at the point of consumption) would be 30 ppm. Therefore the current goals for the iodised salt programme--30-50 ppm iodine appear to be appropriate. However, in adults, children and pregnant women from Abidjan, high urinary iodine levels--levels potentially associated with increased risk of iodine-induced hyperthyroidism--are common. These results suggest an urgent need for improved monitoring and surveillance of the current salt iodisation programme in the Côte d'Ivoire. [ABSTRACT FROM AUTHOR]

Summary Background: Beside their role as the main energy source in the colonic mucosa, short chain fatty acids were found to act as potent antiproliferative and differentiation agents in various cancer cell lines. It has recently been shown that butyrate also induces TGF-β1 mRNA in human keratinocytes, suggesting that TGF-β1 may play a role in butyrate induced cell differentiation. Aim of the study: The objective of our study was to investigate the possible role of exogenous and endogenous TGF-β on butyrate induced differentiation of intestinal epithelium. Methods: Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in standard medium were studied over a 15-day period. Sodium butyrate (5 mM), TGF-β1 (2 ng/ml) or butyrate (5 mM)+anti-human TGF-β1 antibody (30 μg/ml) were added to the medium. At day 4, 8, 11 and 15 total protein content, alkaline phosphatase activity, lactate dehydrogenase activity and transepithelial resistance were measured. Results: Under culture conditions both, butyrate and TGF-β1 inhibited growth accompanied by an induction of cell differentiation approved by increased alkaline phosphatase activity and transepithelial resistance. The differentiating effect of butyrate was accompanied by an increased endogenous TGF-β1, but not TGF-β2 expression in Caco-2 cells. Co-incubation of butyrate with anti-human TGF-β1 antibody suppressed at least in part the differentiating effects of butyrate. Conclusions: Our results directly implicate that the TGF-β isoform TGF-β1 is necessary for butyrate-induced Caco-2 cell differentiation, but other molecular mechanisms may also play a role in the differentiation of this cell line. [ABSTRACT FROM AUTHOR]

Copyright of Rheologica Acta is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The anisotropy of the viscosity and shear-induced structural changes are studied via nonequilibrium molecular dynamics (NEMD) simulations for two types of model liquid crystals which possess both isotropic and smectic phases. These models are (a) perfectly oriented Gay–Berne particles and (b) r−12-soft-spheres plus an r−6-interaction with a P2-anisotropy. Results are presented for the Miesowicz viscosity coefficients in the nematic phase. Presmectic effects are observed. Structural changes are revealed by snapshots of configurations and by the static structure factor, presented in analogy to scattering experiments. The shear-induced transition from the smectic to the nematic phase is analyzed. Similarities between magnetorheological fluids and discotic systems which can form columnar phases are discussed. [ABSTRACT FROM AUTHOR]

The persistent internal quadrupole moment which has been observed in Li-doped ZnO crystals is studied theoretically. The quadrupole moment is expressed in terms of relaxation coefficients and effective cross sections characterizing the scattering and capture processes of the photo carriers. Furthermore, it is related to the anisotropy of the mobility and of the persistent internal polarization. [ABSTRACT FROM AUTHOR]

A theory is presented for the anisotropy of the persistent internal polarization, i.e. for its dependence on the angle between the applied electric field and the c-axis as it has been observed with Li-doped ZnO crystals. Starting point is a Boltzmann equation with anisotropic collision and capture terms. From it, a relation is derived between the ratios of the polarizations for electric fields perpendicular and parallel to the c-axis and of the effective capture cross sections for photo electrons moving parallel and perpendicular to the c-axis. [ABSTRACT FROM AUTHOR]

Cinanserin, 2′-(3-dimethylaminopropylthio)cinnamanilide, was compared in phytohemagglutinin (PHA)-treated human lymphocytes in vitro to two analogs, 2′-(3-dimethylaminopropoxy)-5′-methylcinnamanilide (SQ 11,276) and 5′- tert.-butyl-2′-(3-dimethylaminopropoxy) cinnamanilide (SQ 11,332). These analogs, like cinanserin, exhibit immunosuppressive activity but, unlike cinanserin, possess low antiserotonin activity. Within 1-1.5 hours after addition of the drugs (0.15 m M), incorporation ofH-uridine,C-leucine, andH-thymidine into a macromolecular fraction of PHA-treated cells were inhibited, in an increasing order, by cinanserin, SQ 11,276 and SQ 11,332. At this concentration cellular recovery and viability wre unaltered by cinanserin and SQ 11,276 and substantially decreased by SQ 11,332. SQ 11,332 was less cytotoxic at lower concentrations and 4-7 times more active than cinanserin as an inhibitor of the incorporation of the nucleosides into the macromolecular fraction. [ABSTRACT FROM AUTHOR]

Laparoscopic colposuspension is one of many new operations for treating female urinary stress incontinence. With initially reported success rates similar to those of the traditional open procedure, it appears to combine the advantages of laparoscopy (such as minimal invasiveness and quicker return to normal activities) with the effectiveness of the standard procedure. Different methods and approaches are used, but endoscopic suture techniques remain difficult and time-consuming. The use of endostapling devices for fixation of alloplastic material has been a tempting alternative. We present a case during which laparoscopic colposuspension was performed using staples and mesh. Incontinence did not improve, and the patient suffered severe chronic pain for 18 months postoperatively. Removal of the alloplastic material and traditional abdominal resuspension led to complete cure. [ABSTRACT FROM AUTHOR]

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in refs. 1-3 ). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood 1-3 . Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system 4 . Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.