Good results with cemented total hip arthroplasty in patients between 40 and 50 years of age: 168 hips followed for 2–19 years

Background and purpose Total hip arthroplasties in young patients have lower long-term survival rates than in older patients. We evaluated the use of a unique treatment protocol in patients aged between 40 and 50 years. In all cases we used a cemented THA, and for acetabular deficiencies we also used impacted bone grafts together with a cemented cup

Single transverse-spin asymmetry in Drell-Yan lepton angular distribution

We calculate a single transverse-spin asymmetry for the Drell-Yan lepton-pair's angular distribution in perturbative QCD. At leading order in the strong coupling constant, the asymmetry is expressed in terms of a twist-3 quark-gluon correlation function T_F^{(V)}(x_1,x_2). In our calculation, the same result was obtained in both light-cone and covariant gauge in QCD, while keeping explicit electromagnetic current conservation for the virtual photon that decays into the lepton pair. We also present a numerical estimate of the asymmetry and compare the result to an existing other prediction.Comment: 15 pages, Revtex, 5 Postscript figures, uses aps.sty, epsfig.st

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid-base balance:secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

Sodium-glucose transporter (SGLT)2 inhibitors increase plasma magnesium and plasma phosphate and may cause ketoacidosis, but the contribution of improved glycemic control to these observations as well as effects on other electrolytes and acid-base parameters remain unknown. Therefore, our objective was to compare the effects of SGLT2 inhibitors dapagliflozin and sulfonylurea gliclazide on plasma electrolytes, urinary electrolyte excretion, and acid-base balance in people with Type 2 diabetes (T2D). We assessed the effects of dapagliflozin and gliclazide treatment on plasma electrolytes and bicarbonate, 24-hour urinary pH and excretions of electrolytes, ammonium, citrate, and sulfate in 44 metformin-treated people with T2D and preserved kidney function. Compared with gliclazide, dapagliflozin increased plasma chloride by 1.4 mmol/l (95% CI 0.4-2.4), plasma magnesium by 0.03 mmol/l (95% CI 0.01-0.06), and plasma sulfate by 0.02 mmol/l (95% CI 0.01-0.04). Compared with baseline, dapagliflozin also significantly increased plasma phosphate, but the same trend was observed with gliclazide. From baseline to week 12, dapagliflozin increased the urinary excretion of citrate by 0.93 ± 1.72 mmol/day, acetoacetate by 48 μmol/day (IQR 17-138), and β-hydroxybutyrate by 59 μmol/day (IQR 0-336), without disturbing acid-base balance. In conclusion, dapagliflozin increases plasma magnesium, chloride, and sulfate compared with gliclazide, while reaching similar glucose-lowering in people with T2D. Dapagliflozin also increases urinary ketone excretion without changing acid-base balance. Therefore, the increase in urinary citrate excretion by dapagliflozin may reflect an effect on cellular metabolism including the tricarboxylic acid cycle. This potentially contributes to kidney protection

Whole-body insulin clearance in people with type 2 diabetes and normal kidney function:Relationship with glomerular filtration rate, renal plasma flow, and insulin sensitivity

OBJECTIVE: Kidney insulin clearance, proposed to be the main route of extra-hepatic insulin clearance, occurs in tubular cells following glomerular filtration and peritubular uptake, a process that may be impaired in people with type 2 diabetes (T2D) and/or impaired kidney function. Human studies that investigated kidney insulin clearance are limited by the invasive nature of the measurement. Instead, we evaluated relationships between whole-body insulin clearance, and gold-standard measured kidney function and insulin sensitivity in adults with T2D and normal kidney function. RESEARCH DESIGN AND METHODS: We determined insulin, inulin/iohexol and para-aminohippuric acid (PAH) clearances during a hyperinsulinemic-euglycemic clamp to measure whole-body insulin clearance and kidney function. Insulin sensitivity was expressed by glucose infusion rate (M value). Associations between whole-body insulin clearance, kidney function and insulin sensitivity were examined using univariable and multivariable linear regressions models. RESULTS: We investigated 44 predominantly male (77%) T2D adults aged 63 ± 7, with fat mass 34.5 ± 9 kg, lean body mass 63.0 ± 11.8 kg, and HbA1c 7.4 ± 0.6%. Average whole-body insulin clearance was 1188 ± 358 mL/min. Mean GFR was 110 ± 22 mL/min, mean ERPF 565 ± 141 mL/min, and M value averaged 3.9 ± 2.3 mg/min. Whole-body insulin clearance was positively correlated with lean body mass, ERPF and insulin sensitivity, but not with GFR. ERPF explained 6% of the variance when entered in a nested multivariable linear regression model op top of lean body mass (25%) and insulin sensitivity (15%). CONCLUSIONS: In adults with T2D and normal kidney function, whole-body insulin clearance was predicted best by lean body mass and insulin sensitivity, and to a lesser extent by ERPF. GFR was not associated with whole-body insulin clearance. In contrast to prior understanding, this suggests that in this population kidney insulin clearance may not play such a dominant role in whole-body insulin clearance

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial

AIMS/HYPOTHESIS: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. METHODS: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62.7 ± 6.9 years, HbA1c 7.3 ± 0.7% or 56 ± 1 mmol/mol) were allocated to once daily liraglutide 1.8 mg (n = 17), sitagliptin 100 mg (n = 18) or matching placebos (n = 17) by computer generated numbers. Both participants and researchers were blinded to group assignment. Hepatic fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS). Hepatic fibrosis was estimated using three validated formulae. RESULTS: One patient dropped out in the sitagliptin group owing to dizziness, but no serious adverse events occurred. At week 12, no between-group differences in hepatic steatosis were found. Liraglutide reduced steatosis by 10% (20.9 ± 3.4% to 18.8 ± 3.3%), sitagliptin reduced steatosis by 12.1% (23.9 ± 3.0% to 21.0 ± 2.7%) and placebo lessened it by 9.5% (18.7 ± 2.7% to 16.9 ± 2.7%). Neither drug affected hepatic fibrosis scores compared with placebo. CONCLUSIONS/INTERPRETATION: Twelve-week liraglutide or sitagliptin treatment does not reduce hepatic steatosis or fibrosis in type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01744236 FUNDING : Funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282521 - the SAFEGUARD project

In Defense of Consciousness: The Role of Conscious and Unconscious Inputs in Consumer Choice

Three experiments demonstrate that the same primed construct (e.g., a formal event) has different effects on the subsequent choices of different groups of people (e.g., men and women). Further, these differences in prime effects are attributable to the different associations these groups have with the primed construct. These effects are demonstrated with three different primes and choice domains, and differences in effects are shown with both demographic (e.g., gender) and personality (e.g., extraversion) characteristics. These results highlight the importance of understanding unique, personal associations to primes and demonstrate that segmentation is also important for predicting more automatically driven choices. [url]: http://www.acrwebsite.org/volumes/12797/volumes/v34/NA-34 [copyright notice]: This work is copyrighted by The Association for Consumer Research. For permission to copy or use this work in whole or in part, please contact the Copyright Clearance Center at http://www.copyright.com/. 155 Advances in Consumer Research Volume 34, © 2007 SPECIAL SESSION SUMMARY From First to Second Generation: Moderated Nonconscious Behavior Effects Christian Wheeler, Stanford University, USA SESSION SUMMARY Consumer behavior researchers are becoming increasingly aware of the variety of nonconscious influences on behavior (e.g., The first presentation, by Wheeler and Berger, shows that the same prime can have different, and sometimes opposite effects on choice, depending on the unique personal associations recipients have with the prime. Across three experiments and using both demographic and individual difference segmentation variables, they show that the effects of primes on choices of different groups of people can be predicted by understanding their personal prime associations. The experiments further demonstrate that the differential priming effects are be mediated by the unique personal associations the recipients have with the prime. The second presentation, by Dalton and Chartrand, examines how exposure to relationship partners affects goal pursuit. Whereas previous research has demonstrated that exposure to relationship partners leads to pursuit of the goals they have for the prime recipient, the current studies show that these effects can be reversed. The first study shows that accessibility of overly controlling relationship partners actually leads to pursuit of goals incompatible with those the relationship partner has for recipients, presumably in an attempt to restore personal freedom. The second study lends additional evidence for this account by showing that low reactance individuals pursue the goals of salient relationship partners, but high reactance individuals do not. Hence, reactance can automatically moderate nonconscious goal pursuit and can manifest both as a function of prime targets and individual differences. The final presentation, by Smeesters, Wheeler, and Kay, examines direction of focus as a moderator of whether primes will affect behavior via perceptions of others or more directly. They hypothesized that when features promote focus on other individuals in the situation, perceptions of those individuals will be biased by activated constructs, and changes in behavior will be mediated by such perceptions. When features promote self-focus, on the other hand, behavioral changes will not be mediated by perceptions of other people. Across a series of studies, and using both manipulations and measurements of self-focus vs. other-focus, they supported these hypotheses. Their studies show that primes can generate the same effects on economic decisions, but via different mechanisms, depending on the level of other focus. References EXTENDED ABSTRACTS "Same Prime, Different Effects: Segmentation in Nonconscious Behavior Influence" S. Christian Wheeler, Stanford University Jonah Berger, Stanford University Segmentation has long been recognized as a critical procedure in influencing consumer behavior. The varying needs, wants, experiences, and psychological characteristics of different consumer groups require individualized marketing attempts tailored to these subsets of people. Although the need for segmentation has been widely acknowledged for traditional marketing campaigns, the importance of segmentation for more non-conscious influence attempts has not been recognized. Indeed, one part of the power of such influence techniques is the assumed potential for them to influence different people in similar ways. Because such influence techniques rely on basic associative processes, it has been implicitly assumed that stimuli should exert consistent effects across different types of people. In the present experiments, we demonstrate that the same primes can exert different, and sometimes opposite effects on recipients, depending on the unique personal associations they have to the primed stimulus. Much as unique experiences and associations can affect responses to more deliberate influence attempts, we show that they can also affect less overt influences. Across three studies, and using both demographic and individual difference segmentation variables, we show that different subgroups of consumers exhibit predictable differences in their responses to primes. Specifically, we show that primes can significantly affect consumer choice, but that the effects differ across subgroups of individuals who tend to have different prime associations. The first experiment used the domain of clothing shopping. Pretests indicated that men and women have different shopping associations. Whereas men tend to be more "purpose-driven" or pragmatic and efficient, women tend to be more "possibilitydriven" and browse just to see what is out there. We predicted that these different tendencies, once activated, would influence participants' subsequent choices in an unrelated task. Thus in the main experiment, men and women were randomly assigned to write about either clothes shopping or a control topic (i.e. geography). / From First to Second Generation: Moderated Nonconscious Behavior Effects Then in an ostensibly unrelated study they were asked to make a series of hypothetical choices, some of which between more "purpose-driven" and "possibility-driven" options (e.g., driving a direct route cross-country vs. taking the scenic route). Results indicated that the effect of the prime on subsequent choices differed based on participants' gender; writing about shopping (versus geography) led women to make more possibility-driven choices in the subsequent context whereas it led men to make more purpose-driven choices. The second experiment used the domain of formal events. Pretests indicated that when attending a formal event, men have a goal to dress rather similar to others, whereas women have a goal to dress rather differently from others. Thus in the main experiment, men and women were instructed to write about attending a formal event (or geography) before choosing between different products. Results again indicated different effects of the prime based on gender; women who wrote about the formal event (versus geography) subsequently chose more unique items whereas men who wrote about the formal event tended to choose more common items. In the final experiment, introverts and extroverts were instructed to write about attending a party (or geography) before selecting different items they would like to receive in a drawing. Previous research has demonstrated that introverts and extroverts have different optimal levels of arousal. Introverts are aroused more easily than extroverts. As a result, they prefer lower-arousal situations and tend to be more easily over-aroused than extroverts. Consequently we predicted that thinking about a party would affect the subsequent choice of introverts and extraverts differently; introverts should be subsequently more likely to choose more lowarousal prizes, consistent with their desire to lower arousal at parties, whereas extroverts should be less affected by the prime. Results confirmed this hypothesis. Further, additional analyses showed that these different effects were mediated by the different associations (i.e. level of stimulation) that introverts and extroverts have with parties

The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet

Introduction: Proximal tubule sodium uptake is diminished following sodium glucose cotransporter 2 (SGLT2) inhibition. We previously showed that during SGLT2 inhibition, the kidneys adapt by increasing sodium uptake at distal tubular segments, thereby maintaining body sodium balance. Despite continuous glycosuria, we detected no increased urine volumes. We therefore assessed the adaptive renal responses to prevent excessive fluid loss. Methods: We conducted a mechanistic open-label study in people with type 2 diabetes mellitus with preserved kidney function, who received a standardized sodium intake (150 mmol/d) to evaluate the effects of dapagliflozin on renin-angiotensin-aldosterone system (RAAS) hormones, volume-related biomarkers, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), at start of treatment (day 4), end of treatment (day 14), and follow-up (day 18). Results: A total of 14 people were enrolled. Plasma renin and angiotensin II and urinary aldosterone and angiotensinogen were acutely and persistently increased during treatment with dapagliflozin. Plasma copeptin level was numerically increased after 4 days (21%). Similarly, fractional urea excretion was significantly decreased at start of treatment (−17%). Free water clearance was significantly decreased after 4 days (−74%) and 14 days (−41%). All changes reversed after dapagliflozin discontinuation. Conclusion: Dapagliflozin-induced osmotic diuresis triggers kidney adaptive mechanisms to maintain volume and sodium balance in people with type 2 diabetes and preserved kidney function. ClinicalTrials.gov (identification: NCT03152084)

A Fluorescence Polarization Activity-Based Protein Profiling Assay in the Discovery of Potent, Selective Inhibitors for Human Nonlysosomal Glucosylceramidase

Human nonlysosomal glucosylceramidase (GBA2) is one of several enzymes that controls levels of glycolipids and whose activity is linked to several human disease states. There is a major need to design or discover selective GBA2 inhibitors both as chemical tools and as potential therapeutic agents. Here, we describe the development of a fluorescence polarization activity-based protein profiling (FluoPol-ABPP) assay for the rapid identification, from a 350+ library of iminosugars, of GBA2 inhibitors. A focused library is generated based on leads from the FluoPol-ABPP screen and assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA), and the cytosolic retaining β-glucosidase, GBA3. Our work, yielding potent and selective GBA2 inhibitors, also provides a roadmap for the development of high-throughput assays for identifying retaining glycosidase inhibitors by FluoPol-ABPP on cell extracts containing recombinant, overexpressed glycosidase as the easily accessible enzyme source

No positive effect of autologous platelet gel after total knee arthroplasty: A double-blind randomized controlled trial: 102 patients with a 3-month follow-up

Background and purpose Activated platelets release a cocktail of growth factors, some of which are thought to stimulate repair. We investigated whether the use of autologous platelet gel (PG) in total knee arthroplasty (TKA) would improve wound healing and knee function, and reduce blood loss and the use of analgesics. Patients and methods 102 patients undergoing TKA were randomly assigned to a PG group (n 50) or to a control (C) group (n 52). The primary analysis was based on 73 participants (PG: 32; C: 41) with comparison of postoperative wound scores, VAS, WOMAC, knee function, use of analgesics, and the pre- and postoperative hemoglobin values after a follow-up of 3 months. 29 participants were excluded due to insufficient data. Results The characteristics of the protocol-compliant patients were similar to those of the patients who w