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Secondary metabolites often function as antipredator defenses, but when bioactive at low concentrations, their off-target effects on other organisms may be overlooked. Candidate "keystone molecules" are proposed to affect community structure and ecosystem functions, generally originating as defenses of primary producers; the broader effects of animal chemistry remain largely unexplored, however. Here, we characterize five previously unreported polyketides (alderenes A to E) biosynthesized by sea slugs reaching exceptional densities (up to 9000 slugs per square meter) in Northern Hemisphere estuaries. Alderenes comprise only 0.1% of slug wet weight, yet rendered live slugs or dead flesh unpalatable to three co-occurring consumers, making a potential food resource unavailable and redirecting energy flow in critical nursery habitat. Alderenes also displaced infauna from the upper sediment of the mudflat but attracted ovipositing snails. By altering communities, such compounds may have unexpected cascading effects on processes ranging from bioturbation to reproduction of species not obviously connected to the producing organisms, warranting greater attention by ecologists.

Objective: The quality of histopathological specimens obtained from the upper urinary tract with conventional flexible ureterorenoscopic biopsy needs to be improved. We investigated the feasibility and biopsy quality of specimens obtained by cryobiopsy, compared with standard ureterorenoscopic biopsy techniques in a human ex vivo model., Materials and Methods: Human ureters obtained from nephrectomy specimens (N=12) were dissected and canulated with an ureteral access sheath. Ureterorenoscopic biopsies were randomly obtained from different sites of the renal pelvic caliceal system using different types of instruments. The performance of two newly developed flexible cryoprobes with outer diameters of 1.1 mm (CB11) and 0.9 mm (CB09) was compared with that of the biopsy forceps(FB) and Bigopsy®(BiG) and two different Dormia baskets N-Gage (NG) and Zero-Tip (ZT). We assessed the feasibility of the various biopsy techniques based on the number of biopsy attempts needed to obtain macroscopically discernible biopsies. The specimens were examined histopathologically for size, biopsy quality, presence of various artifact types, and representativeness., Results: Biopsies taken with the cryoprobes showed a higher biopsy quality than biopsies taken with the comparative instruments. The CB11 provided significantly larger biopsies than forceps biopsies and also than biopsies with ZT. The CB09 was able to collect larger samples when compared with the FB and BiG biopsy forceps. There were no significant differences in artifact area, except for the CB11 cryoprobe compared with the NG. To clarify the results a subdivision of larger or smaller than 20% artifact area was performed. A significant difference was found between CB11 and the forceps biopsies, as well as between CB11 and NG and ZT in favor of the cryoprobe. The representation of the histopathological sample was also determined. Biopsies taken with CB11 were more representative compared with forceps biopsies BiG and FB and basket biopsies NG and ZT., Conclusions: In a standardized comparative ex vivo setting, larger biopsies were obtained by using the cryobiopsy technique with the CB11 probe. Qualitatively, cryobiopsy specimens were overlaid by fewer artifacts and a higher biopsy quality was achieved in histopathologic examination compared with standard instrumentation. Further stepwise development will transfer the promising cryobiopsy technique into the clinical setting., Competing Interests: ME and WL are employed by Erbe Elektromedizin GmbH, Tuebingen Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Klein, John, Bohnert, Enderle, Linzenbold and Bolenz.)

Purpose: The use of reverse shoulder arthroplasty (RSA) to treat complex humerus fractures is increasing, especially in older, osteoporotic patients. Refixation and tuberosity healing are needed to achieve an optimal range of motion (ROM), external rotation, active forward elevation, and patient satisfaction. Proper healing has been reported, however, in only 40-84% of cases. Our study's aim was to describe a simple, reproducible fixation technique designed to improve tuberosity healing., Methods: We included 30 patients with acute proximal humerus fractures undergoing RSA (Global Unite Reverse Fracture, DePuy Synthes, Warsaw, IN, USA) with tuberosity reattachment. The humerus stem was cemented in 24 cases. A standardized suture technique with two fiber tapes was used to reattach tuberosities. Clinical and radiological parameters, which were collected one year post-operatively, included ROM, pain level, Constant scores, subjective shoulder value (SSV), and tuberosity healing., Results: The mean age of the patients was 79.3 years (± 7; range 65-92), and the tuberosity healing rate was 90.0% (27 of 30). Two patients showed migration (one nonunion, one malunion), and another had complete resorption after an initial period of proper healing. Radiolucent lines around the humerus stem occurred in one case, and three patients had scapular notching. The mean SSV was 86% (± 11; range 60-100), the Constant score was 72 (± 10.3; range 48-92), the active forward flexion was 140° (± 14.3; range 115-165), and external rotation was 23° (± 16.5; range 0-50)., Conclusions: This reattachment technique, which is simple and reproducible, achieved a higher tuberosity healing rate than previously published rates.

Rare anatomical variants in the human knee joint include the anomalous insertion of the medial meniscus (AIMM) into the anterior cruciate ligament (ACL) or the presence of a triple bundle ACL. The functional implications of those anomalies have not yet been fully elucidated and might be important in reconstructive surgery of the damaged knee. We report the case of a 35-year-old female patient with an AIMM into a triple bundle ACL associated with tears of the medial meniscus in both of her knees. Arthroscopic partial meniscectomy was performed on one side, and conservative treatment with physiotherapy was chosen for the other side with good clinical outcomes., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that they have no competing interests to declare., (© 2020 The Authors.)

The purpose of the present study was to biomechanically compare the primary stability of our formerly described inside-out plate fixation to the classic double screw fixation for scarf osteotomy in the treatment of hallux valgus. We performed 20 scarf osteotomies on first metatarsal composite bone models. One half were fixed using a double screw technique and the other half using a locking plate inside-out technique. Using a testing device to simulate the physiologic load, the specimen was loaded until failure, and the load at failure, displacement at failure, and work at failure were recorded. The results were compared between the 2 groups and against the findings from intact sawbones. Compared with the intact bone models, the energy absorption was low for both types of osteotomy fixation. Between the 2 fixation groups, the load at failure was greater for plate fixation, although the difference was not statistically significant (p = .051). However, a statistically significant difference was found between both groups comparing work and displacement at failure (p < .001). In conclusion, the formerly described inside-out plating technique is a biomechanically reasonable alternative to screw fixation because of its primary stability after scarf osteotomy for hallux valgus., (Copyright © 2018 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Scope: Curcuminoids are poorly bioavailable, but potentially lipid- and inflammation-lowering phytochemicals. We hypothesized that curcuminoids, when administered as a micellar formulation with hundredfold enhanced bioavailability, decrease blood lipids and inflammation in subjects with moderately elevated cholesterol and C-reactive protein concentrations., Methods and Results: We carried out a randomized, double-blind, crossover study (4-wk washout phase) with 42 subjects consuming 294 mg curcuminoids per day (as micelles) or placebo for 6 wk. At the beginning, after 3 wk and at the end (6 wk) of each intervention, we collected fasting blood samples to determine curcuminoids, blood lipids, and markers of inflammation, glucose and iron homeostasis, and liver toxicity. Daily ingestion of 98 mg micellar curcuminoids with each principal meal for as little as 3 wk resulted in fasting curcuminoid plasma concentrations of 49 nmol/L. Neither blood lipids, nor markers of inflammation, glucose and iron homeostasis, or liver enzymes differed between curcuminoid and placebo interventions., Conclusion: Consumption of 98 mg of highly bioavailable curcuminoids with each principal meal sufficed to achieve curcuminoid accumulation in the blood, was safe, and did not alter blood lipids, inflammation, glucose, or iron homeostasis in healthy subjects with slightly elevated blood cholesterol and C-reactive protein., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity-from molecular, to physiological, to social. Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data. A White Adipose Tissue Health Reference Network (WATRefNet) was constructed as a resource for discovery and prioritization of mechanism-based biomarkers for white adipose tissue (WAT) health status and the effect of food and drug compounds on WAT health status. The WATRefNet (6,797 nodes and 32,171 edges) is based on (1) experimental data obtained from 10 studies addressing different adiposity states, (2) seven public knowledge bases of molecular interactions, (3) expert's definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and (4) a collection of relevant biomarkers of these processes identified by BIOCLAIMS ( http://bioclaims.uib.es ). The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions. We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes. Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet. This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.

Introduction: Total hip arthroplasty (THA) is one of the most frequently performed procedures in orthopaedics and weakness of external rotators is often recognized thereafter. However, the etiology of lateral hip pain is multifaceted. For the diagnosis of abductor tendon rupture, magnetic resonance imaging (MRI) is the gold standard. As not every patient can be subjected to MRI, a clinical diagnostic test for easy detection of lesions of the abductor tendon is missing. Here, we present the internal rotation lack sign indicating abductor tendon pathology., Methods: The patient is placed in lateral position on a stretcher with hips and knees in neutral position. The knee is flexed to 45° and the hip passively abducted and elevated by the investigator. With the foot passively abducted, the patient is then asked to bring his knee in direction to the examination table. This motion is also tested passively. The test is regarded positive, if no internal rotation is possible and/or if this is painful. If groin pain is elicited during either of the exercises, the test is also rated positive., Results: We evaluated this test in 20 patients clinically and by magnetic resonance imaging (MRI). All patients demonstrated a positive internal rotation lag sign. Twelve of them lag of internal rotation and evidence of anterior abductor tendon rupture on MRI, 8 with lag of internal rotation and no evidence of abductor tendon rupture., Conclusion: The new clinical diagnostic sign presented here may improve the diagnosis of abductor tendon rupture in the future., Level of Evidence: Diagnostic study, level I.