bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactomedin-4 improves cutaneous wound healing by promoting skin cell proliferation and migration through POU5F1/OCT4 and ESR1 signalling cascades
Authors: Klaas Mariliis , Mäemets-Allas Kristina , Heinmäe Elizabeth , Lagus Heli , Arak Terje , Eller Mart , Kingo Külli , Kankuri Esko , Jaks Viljar
Published: February 2022

Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein, which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we investigated its role in skin regeneration. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 selectively stimulated keratinocyte proliferation and increased both keratinocyte and fibroblast migration. Using proteotranscriptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-induced signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing efficacy. Taken together, our results suggest that OLFM4 acts as a transiently upregulated inflammatory signal that promotes wound healing by regulating both dermal and epidermal cell compartments of the skin.
Vibration of an Incompressible viscoelastic shell of rate type
Authors: Farina Angiolo , Fusi Lorenzo , Rosso Fabio , Saccomandi Giuseppe
Published: February 2022

We study the oscillations of a spherical shell of a rate-type viscoelastic solid subject to a pressure difference between the inner and the outer surface. The stable equilibrium configurations, in the class of spherically symmetric deformations, correspond to the minima of the elastic energy function. Numerical simulations indicate that the way in which the equilibrium state is reached, strongly depends on the material parameters.
Social cognitive mechanisms in healthcare worker resilience across time during the pandemic
Authors: Smith Andrew J. , Shoji Kotaro , Griffin Brandon J. , Sippel Lauren M. , Dworkin Emily R. , Wright Hannah M. , Morrow Ellen , Locke Amy , Love Tiffany M. , Harris J. Irene , Kaniasty Krzysztof , Langenecker Scott A. , Benight Charles C.
Published: February 2022

Purpose

Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models.

Methods

Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy).

Results

The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity.

Conclusions

Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events.
Excellent clinical and radiological outcomes after both open flake refixation and autologous chondrocyte implantation following acute patella dislocation and concomitant flake fractures
Authors: Ehmann Yannick J. , Zuche Lea , Schmitt Andreas , Berthold Daniel P. , Rupp Marco-Christopher , Muench Lukas N. , Otto Alexander , Woertler Klaus , Imhoff Andreas B. , Mehl Julian
Published: February 2022

Purpose

To investigate clinical and magnetic resonance (MR) imaging results of patients undergoing patella stabilization with either open flake refixation (oFR) or autologous chondrocyte implantation (ACI) and concomitant soft tissue patella stabilization after sustaining primary, acute patella dislocation with confirmed chondral and/or osteochondral flake fractures. It was hypothesized that refixation will lead to better results than ACI at mid-term follow-up.

Methods

A retrospective chart review was conducted to identify all patients undergoing oFR or ACI after sustaining (osteo-)chondral flake fractures and concomitant soft tissue patella stabilization following primary, acute patella dislocation between 01/2012 and 09/2018 at the author’s institution. Patients were excluded if they were aged < 14 years or > 30 and had previous knee surgeries at the index knee. Clinical outcomes were assessed using the Tegner activity score, Kujala score, subjective IKDC score, and the KOOS score at a minimum follow-up of 24 months postoperatively. MR images were assessed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 knee score. Thirty patients were included in the study, with 16 patients assorted to the oFR group and 14 patients to the ACI group (Follow-up 81%).

Results

Demographic data did not show significant group differences (oFR: 6 females, 10 males; age 26.9 ± 5.6 years, FU: 57 months (27–97 months); ACI: 9 females, 5 males; age 25.5 ± 4.9 years, FU: 51 months (29–91 months); n.s.). Defect location was similar in both groups (oFR: 12 × patella/4 × lateral femoral condyle; ACI: 12/2; n.s.). Both groups showed excellent clinical outcomes, with no statistically significant difference between both the groups (oFR group vs. ACI group: Tegner: 5.1 ± 1.8 vs. 5.1 ± 1.4; Kujala: 86.1 ± 12.6 vs. 84.9 ± 9.1; IKDC: 83.8 ± 15.0 vs. 83.6 ± 11.3; KOOS: 83.3 ± 14.0 vs. 83.6 ± 12.0; n.s.). One patient in each group suffered a patella re-dislocation and needed revision surgery. The MOCART 2.0 score showed good results for the oFR group (68.2 ± 11.1) and the ACI group (61.1 ± 16.9) while no significant differences were noted between both the groups. The inter-rater reliability was excellent (0.847).

Conclusion

Open refixation of (osteo-)chondral fragments in patients after sustaining acute patella dislocation with (osteo)-chondral flake fractures led to good clinical and radiological results at a minimum follow of 24 months, showing that it is a good surgical option in the treatment algorithm. However, if open refixation is not possible, ACI may be an excellent fallback option in these younger patients with equally good clinical and radiological outcomes, but requiring a second minimally invasive surgery.

Level of evidence

III.
Effect of electroacupuncture on the degradation of collagen in pelvic floor supporting tissue of stress urinary incontinence rats
Authors: Li Chaonan , Yang Mengyi , Qu Zhiyu , Ruan Shuoquan , Chen Bingli , Ran Jinchuan , Shu Wen , Chen Yuelai , Hou Wenguang
Published: February 2022

Introduction and hypothesis

To examine the changes induced by electroacupuncture in stress urinary incontinence (SUI) rats, including the urodynamics and collagen degradation-related cytokine molecular biological expression changes, and to explore the effect and mechanism of EA treatment in SUI.

Methods

Female SPF Sprague-Dawley rats were randomly assigned to five groups (n = 10): sham, model, electroacupuncture control, electroacupuncture, and blocker. The leak point pressure (LPP) and maximum bladder capacity (MBC) were measured for each group of rats, and collagen I, collagen III, matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMPs) in the anterior vaginal wall of rats in each group were determined by reverse transcription-polymerase chain reaction and western blotting. The data were analyzed by one-way analysis of variance or Kruskal-Wallis test.

Results

Electroacupuncture Shenshu (BL23) and Huiyang (BL35) increased the LPP and MBC in SUI rats (P < 0.05). Electroacupuncture treatment significantly increased the protein expression of collagen I and collagen III in the anterior vaginal wall of SUI rats (P < 0.05) and significantly reduced the protein expression of MMP1, MMP2, and MMP9 (P < 0.05).

Conclusions

Electroacupuncture stimulation can alleviate the signs of SUI, and its mechanism is related to the degradation of collagen in the anterior vaginal wall.
Development of reconstructed intestinal micronucleus cytome (RICyt) assay in 3D human gut model for genotoxicity assessment of orally ingested substances
Authors: Lim Hui Kheng , Hughes Christopher Owen , Lim Michelle Jing Sin , Li Jia’En Jasmine , Rakshit Moumita , Yeo Calvin , Chng Kern Rei , Li Angela , Chan Joanne Sheot Harn , Ng Kee Woei , Leavesley David Ian , Smith Benjamin Paul Chapman
Published: February 2022

The micronucleus (MN) assay is widely used as part of a battery of tests applied to evaluate the genotoxic potential of chemicals, including new food additives and novel food ingredients. Micronucleus assays typically utilise homogenous in vitro cell lines which poorly recapitulate the physiology, biochemistry and genomic events in the gut, the site of first contact for ingested materials. Here we have adapted and validated the MN endpoint assay protocol for use with complex 3D reconstructed intestinal microtissues; we have named this new protocol the reconstructed intestine micronucleus cytome (RICyt) assay. Our data suggest the commercial 3D microtissues replicate the physiological, biochemical and genomic responses of native human small intestine to exogenous compounds. Tissues were shown to maintain log-phase proliferation throughout the period of exposure and expressed low background MN. Analysis using the RICyt assay protocol revealed the presence of diverse cell types and nuclear anomalies (cytome) in addition to MN, indicating evidence for comprehensive DNA damage and mode(s) of cell death reported by the assay. The assay correctly identified and discriminated direct-acting clastogen, aneugen and clastogen requiring exogenous metabolic activation, and a non-genotoxic chemical. We are confident that the genotoxic response in the 3D microtissues more closely resembles the native tissues due to the inherent tissue architecture, surface area, barrier effects and tissue matrix interactions. This proof-of-concept study highlights the RICyt MN cytome assay in 3D reconstructed intestinal microtissues is a promising tool for applications in predictive toxicology.
Approximation types describing extensions of valuations to rational function fields
Authors: Kuhlmann F.-V.
Published: February 2022

We introduce the notion of approximation type for the partial, and in certain cases the total description of extensions of a given valuation from a field K to the rational function field K(x). To every extension, a unique approximation type of x over K is associated, while x may be the limit of many pseudo Cauchy sequences. Approximation types also provide information in cases where the extensions are not immediate, and we prove that they correspond bijectively to the extensions when K is algebraically closed or, more generally, lies dense in its algebraic closure with respect to the topology induced by the valuation.
The Hawking–Penrose Singularity Theorem for $$C^1$$-Lorentzian Metrics
Authors: Kunzinger Michael , Ohanyan Argam , Schinnerl Benedict , Steinbauer Roland
Published: February 2022

We extend both the Hawking–Penrose theorem and its generalisation due to Galloway and Senovilla to Lorentzian metrics of regularity $$C^1$$

C
1

. For metrics of such low regularity, two main obstacles have to be addressed. On the one hand, the Ricci tensor now is distributional, and on the other hand, unique solvability of the geodesic equation is lost. To deal with the first issue in a consistent way, we develop a theory of tensor distributions of finite order, which also provides a framework for the recent proofs of the theorems of Hawking and of Penrose for $$C^1$$

C
1

-metrics (Graf in Commun Math Phys 378(2):1417–1450, 2020). For the second issue, we study geodesic branching and add a further alternative to causal geodesic incompleteness to the theorem, namely a condition of maximal causal non-branching. The genericity condition is re-cast in a distributional form that applies to the current reduced regularity while still being fully compatible with the smooth and $$C^{1,1}$$

C

1
,
1

-settings. In addition, we develop refinements of the comparison techniques used in the proof of the $$C^{1,1}$$

C

1
,
1

-version of the theorem (Graf in Commun Math Phys 360:1009–1042, 2018). The necessary results from low regularity causality theory are collected in an appendix.
Fighting ability and the toxicity of raiding pheromone in an obligate kleptoparasite, the stingless bee Lestrimelitta niitkib
Authors: James Chase C. , Sánchez Daniel , Cruz-López Leopoldo , Nieh James
Published: February 2022

The evolution of obligate kleptoparasitism, the theft of food, has led to remarkable innovations, including physical weapons and chemical signals that can evolve into chemical weapons. Stingless bees in the genus Lestrimelitta are excellent examples of this phenomenon because they are obligate kleptoparasites that no longer collect floral resources and instead steal brood resources from other bees. Their ability to raid successfully is thus essential to their fitness even when they fight species that are physically bigger, have larger defense forces, or both. We conducted morphometric analyses, quantified Lestrimelitta niitkib mandibular gland pheromone (MGP) components, and carried out individual fighting trials between L. niitkib and the stingless bee Scaptotrigona mexicana, a common victim species, to shed light on the detailed reasons for their success at robbing. Measurements showed that L. niitkib mandibles have thicker exoskeleton cuticles and overall greater width, particularly in the medial and proximal sections, than S. mexicana, which is quite similar in body size. In all fights, L. niitkib bit victims and released MGP, as it does during raids. Scaptotrigona mexicana victims exhibited significantly increased uncoordinated behaviors and showed partial or complete paralysis. We analyzed and quantified the major components of MGP, which consisted of large quantities of geranial (mean of 253 μg) and neral (48 μg) per bee. Microinjections of 1 bee equivalent (BE) of natural or synthetic MGP and ≥ 0.1 BE of geranial significantly increased deleterious behaviors and paralysis as compared to control injections. We suggest that the large quantities of MGP used during raiding have led to an unexpected outcome, a semiochemical evolving the additional function of a toxin, and contribute to the ability of Lestrimelitta to rob its victims.

Significance statement

Kleptoparasites, organisms that steal food resources, employ multiple physical and chemical tools to survive. The success of kleptoparasitism requires a balance between honesty and coercion in interspecific communication. The genus Lestrimellita consists of a group of kleptoparasitic stingless bee species that raid other bee colonies for food and therefore depend upon winning these raids. However, why they succeed remains not fully understood. We studied differences in morphology between L. niitkib and its victims, the pheromones they release during raids, and ran individual fight trials between L. niitkib and a common victim to identify why they are successful. We suggest that the release of pheromones at the beginning of raids, in concert with the pheromone’s toxicity, has been combined to improve L. niitkib’s ability to successfully rob.
Impact on Patient’s Appearance Perception of Autologous and Implant Based Breast Reconstruction Following Mastectomy Using BREAST-Q
Authors: Persichetti Paolo , Barone Mauro , Salzillo Rosa , Cogliandro Annalisa , Brunetti Beniamino , Ciarrocchi Silvia , Alessandri Bonetti Mario , Tenna Stefania , Sorotos Michail , Santanelli Di Pompeo Fabio
Published: February 2022

Introduction

The purpose of this study is to determine if there is a better quality of life with one of the two techniques and if the results are in line with those already present in the literature. The hypothesis from which we started is to demonstrate that cancer patients who undergo a deep inferior epigastric perforator flap (DIEP) breast reconstruction surgery are more satisfied and have a higher level of quality of life compared to those subjected to an intervention of reconstruction with prosthesis.

Materials and Methods

All patients undergoing reconstruction from January 2010 to July 2018 were eligible for inclusion. This is a retrospective cohort study carried out using the patients of two plastic surgery departments who have undergone monolateral or bilateral implant-based or DIEP flap breast reconstruction. We administered BREAST-Q questionnaire electronically almost 2 year after surgery. Patients were divided into two groups: implant-based and autologous breast reconstruction with DIEP flaps. Baseline demographics and patient characteristics were analyzed using a Students t-test (continuous variables) or Chi-square/Fisher’s exact test (categorical variables). Mean standard deviation BREAST-Q scores were reported for the overall cohort and by modality for the postoperative period. The linear regression model was applied to all BREAST-Q score with all predictor factors.

Results

Of the 1125 patients involved, only 325 met the inclusion criteria and were enrolled in this study; specifically, 133 (41%) DIEP and 192 (59%) prosthetic reconstructions. We summarized the results of the principal scales of BREAST-Q module: satisfaction with breast, psychosocial well-being, satisfaction with outcome, and sexual well-being in which the autologous group was always more satisfied. We reported results of all linear regression models with higher values for the DIEP group independently from predictors.

Conclusion

This is the first study performed on the Italian population that compares autologous surgical techniques with the implantation of breast implants. In this population, DIEP is considered the technique that leads to the highest satisfaction in all BREAST-Q scores.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Laparoscopic Heller Myotomy and Toupet Fundoplication
Authors: Alimi Yewande R. , Esquivel Micaela M. , Hawn Mary T.
Published: February 2022

Esophageal achalasia is a primary motility disorder of unknown origin. The goal of treatment is to eliminate the resistance caused by a non‐relaxing lower esophageal sphincter, therefore allowing passage of food and liquid from the esophagus into the stomach. A myotomy with a partial fundoplication (anterior Dor or posterior Toupet) is considered the standard of care for patients with achalasia. In the following review, we describe the indications and technique for a posterior partial fundoplication (Toupet).
Acute pain after total hip and knee arthroplasty does not affect chronic pain during the first postoperative year: observational cohort study of 389 patients
Authors: Latijnhouwers D. A. J. M. , Martini C. H. , Nelissen R. G. H. H. , Verdegaal S. H. M. , Vliet Vlieland T. P. M. , Gademan M. G. J. ,   the Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study (LOAS) Group, van der Linden H. M. J. , Kaptein B. L. , Damen P. J. , Kaptijn H. H. , Vehmeijer S. B. W. , Marijnissen W. C. M. , Onstenk R.
Published: February 2022

Chronic pain is frequently reported after total hip and knee arthroplasties (THA/TKA) in osteoarthritis (OA) patients. We investigated if severity of acute postoperative pain following THA/TKA in OA patients was associated with pain during the first postoperative year. From an observational study, OA patients scheduled for primary THA/TKA (June 2012–December 2017) were included from two hospitals in the Netherlands. Acute postoperative pain scores were collected within 72 h postoperatively and categorized as no/mild (NRS ≤ 4) or moderate/severe (NRS > 4). Pain was assessed preoperatively, 3, 6 and 12 months postoperatively using the HOOS/KOOS subscale pain. With Multilevel Mixed-effects-analyses, we estimated associations between acute and chronic pain until one year postoperative, adjusted for confounders and including an interaction term (Time*Acute pain). 193 THA and 196 TKA patients were included, 29% of THA and 51% of TKA patients reported moderate/severe pain acutely after surgery. In the THA group, the difference in pain at 3 months between the no/mild and moderate/severe groups, was approximately six points, in favor of the no/mild group (95% CI [−12.4 to 0.9]) this difference became smaller over time. In the TKA group we found similar differences, with approximately four points (95% CI [−9.6 to 1.3]) difference between the no/mild and moderate/severe group at 6 months, this difference attenuated at 12 months. No association between severity of acute postoperative pain and pain during the first postoperative year was found. These findings suggest that measures to limit acute postoperative pain will likely not impact development of chronic pain.
Maximal Convergence and Interpolation on Unconnected Sets
Authors: Blatt Hans-Peter
Published: February 2022

A theorem of Grothmann states that interpolating polynomials to a holomorphic function on a compact set E is maximally convergent to f only if a subsequence of the interpolation points converges to the equilibrium distribution of E in the weak* sense. Grothmann’s proof applies only for connected sets E. The objective of this paper is to provide a new necessary condition for maximal convergence which is the crucial tool to prove Grothmann’s theorem for unconnected sets E.
Patient satisfaction, joint stability and return to sports following simple elbow dislocations: surgical versus non-surgical treatment
Authors: Geyer Stephanie , Lacheta Lucca , Seilern und Aspang Jesse , Willinger Lukas , Lutz Patricia M. , Lappen Sebastian , Imhoff Andreas B. , Siebenlist Sebastian
Published: February 2022

Purpose

While conservative management is commonly promoted for simple elbow dislocations, the importance of primary surgical treatment in these injuries is still undetermined. The objective of this study was to report patient-reported outcome measures (PROMs), return to sports (RTS) and joint stability using ultrasound in patients following conservative or surgical treatment after simple elbow dislocation.

Methods

Patients with a minimum follow-up of 24 months after conservative (CT) or surgical treatment (ST) following simple elbow dislocation were included in this retrospective study. To evaluate patients’ postoperative outcome and satisfaction, the Elbow Self-Assessment Score (ESAS) was used, and validated scores such as the Mayo elbow performance score (MEPS), the Quick Disability of Arm and Shoulder Score (Quick-DASH) and RTS were assessed. For objective assessment of residual joint instability, a standardized clinical examination as well as a dynamic ultrasound evaluation of the affected and the contralateral elbow was performed.

Results

Forty-four patients (26 women, 18 men) with an average age of 41.5 ± 15.3 years were available for follow-up survey (65.5 ± 30.4 months; range 26–123). 21 patients were treated conservatively and twenty-three patients received surgical treatment. CT and ST resulted in similar outcome with regard to ROM, ESAS (CT: 99.4 ± 1.5; ST: 99.8 ± 0.3), MEPS (CT: 97.3 ± 6.8 points; ST: 98.7 ± 3.3) and Quick-DASH (CT: 7.8 ± 10.4; ST: 6.3 ± 7.9) (n.s.). There was no difference in elbow stability and laxity measured by ultrasound between the study groups and compared to the healthy elbow (n.s.). Two patients of the CT group (10%) complained about persistent subjective elbow instability. RTS was faster after surgical compared to conservative treatment (p = 0.036).

Conclusion

Both, conservative and surgical treatment results in high patient satisfaction and good-to-excellent functional outcome after simple elbow dislocation. Even though ultrasound evaluation showed no significant differences in joint gapping between groups, 10% of conservatively treated patients complained about severe subjective instability. Surgically treated patients returned faster to their preoperatively performed sports. Thus, primary surgical treatment may be beneficial for high demanding patients.

Level of evidence

Therapeutic study, Level III.
Retinometer predicts visual outcome in Descemet membrane endothelial keratoplasty
Authors: Wald Caroline Sophie , Unterlauft Jan Darius , Rehak Matus , Girbardt Christian
Published: February 2022

Purpose

To analyze the preoperative predictive value of retinometer visual acuity (VA) in eyes following Descemet membrane endothelial keratoplasty (DMEK).

Methods

Patients undergoing DMEK between August 2011 and July 2020 were included. Preoperative interference visual acuity was assessed using Heine Lambda 100 Retinometer. Depending on the presence or absence of concomitant ocular disease, the Retinometer was evaluated for its ability to preoperatively predict best-corrected visual acuity (BCVA) six months after surgery using correlation, simple and multiple linear regression, contingency analyses, and receiver operating characteristic (ROC) analysis. Preoperative corneal backscatter was correlated with Retinometer prediction accuracy.

Results

A total of 198 eyes were included in the analysis. There was a significant correlation between Retinometer VA and postoperative BCVA (r = 0.647, P < 0.001). Regardless of the presence or absence of concomitant ocular disease and the surgery procedure (DMEK & triple DMEK), Retinometer VA was the most significant predictor of postoperative BCVA (P < 0.001). ROC analysis revealed reliable diagnostic performance of the Retinometer (AUC = 0.829, P < 0.001). A Retinometer VA ≥ 0.5 accurately predicted a postoperative BCVA ≥ 0.5 in 91% of cases. No association was found between corneal backscatter and prediction accuracy (P = 0.566).

Conclusions

Retinometer VA can be used for preoperative prediction of postoperative BCVA in DMEK and triple DMEK patients, independent of increased backscatter values and the presence or absence of concomitant ocular disease. By using this simple but effective tool, indication for DMEK can be facilitated and postoperative outcomes can be realistically predicted preoperatively.
Angiotensin II type 1 receptor localizes at the blood–bile barrier in humans and pigs
Authors: Pryymachuk Galyna , El-Awaad Ehab , Piekarek Nadin , Drebber Uta , Maul Alexandra C. , Hescheler Juergen , Wodarz Andreas , Pfitzer Gabriele , Neiss Wolfram F. , Pietsch Markus , Schroeter Mechthild M.
Published: February 2022

Animal models and clinical studies suggest an influence of angiotensin II (AngII) on the pathogenesis of liver diseases via the renin–angiotensin system. AngII application increases portal blood pressure, reduces bile flow, and increases permeability of liver tight junctions. Establishing the subcellular localization of angiotensin II receptor type 1 (AT1R), the main AngII receptor, helps to understand the effects of AngII on the liver. We localized AT1R in situ in human and porcine liver and porcine gallbladder by immunohistochemistry. In order to do so, we characterized commercial anti-AT1R antibodies regarding their capability to recognize heterologous human AT1R in immunocytochemistry and on western blots, and to detect AT1R using overlap studies and AT1R-specific blocking peptides. In hepatocytes and canals of Hering, AT1R displayed a tram-track-like distribution, while in cholangiocytes AT1R appeared in a honeycomb-like pattern; i.e., in liver epithelia, AT1R showed an equivalent distribution to that in the apical junctional network, which seals bile canaliculi and bile ducts along the blood–bile barrier. In intrahepatic blood vessels, AT1R was most prominent in the tunica media. We confirmed AT1R localization in situ to the plasma membrane domain, particularly between tight and adherens junctions in both human and porcine hepatocytes, cholangiocytes, and gallbladder epithelial cells using different anti-AT1R antibodies. Localization of AT1R at the junctional complex could explain previously reported AngII effects and predestines AT1R as a transmitter of tight junction permeability.
A century of exercise physiology: key concepts on coupling respiratory oxygen flow to muscle energy demand during exercise
Authors: Ferretti Guido , Fagoni Nazzareno , Taboni Anna , Vinetti Giovanni , di Prampero Pietro Enrico
Published: February 2022

After a short historical account, and a discussion of Hill and Meyerhof’s theory of the energetics of muscular exercise, we analyse steady-state rest and exercise as the condition wherein coupling of respiration to metabolism is most perfect. The quantitative relationships show that the homeostatic equilibrium, centred around arterial pH of 7.4 and arterial carbon dioxide partial pressure of 40 mmHg, is attained when the ratio of alveolar ventilation to carbon dioxide flow ($${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$V˙A/V˙RCO2) is − 21.6. Several combinations, exploited during exercise, of pertinent respiratory variables are compatible with this equilibrium, allowing adjustment of oxygen flow to oxygen demand without its alteration. During exercise transients, the balance is broken, but the coupling of respiration to metabolism is preserved when, as during moderate exercise, the respiratory system responds faster than the metabolic pathways. At higher exercise intensities, early blood lactate accumulation suggests that the coupling of respiration to metabolism is transiently broken, to be re-established when, at steady state, blood lactate stabilizes at higher levels than resting. In the severe exercise domain, coupling cannot be re-established, so that anaerobic lactic metabolism also contributes to sustain energy demand, lactate concentration goes up and arterial pH falls continuously. The$${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$V˙A/V˙RCO2decreases below − 21.6, because of ensuing hyperventilation, while lactate keeps being accumulated, so that exercise is rapidly interrupted. The most extreme rupture of the homeostatic equilibrium occurs during breath-holding, because oxygen flow from ambient air to mitochondria is interrupted. No coupling at all is possible between respiration and metabolism in this case.
Solidarity, support and acceptance: a celebration of the person, not the disease
Authors: Page Tamara
Published: February 2022

St Andrew’s Hospital provides care for more than 700 patients diagnosed with breast cancer annually. Each person’s experience is individual, but created by their interactions with the healthcare providers from diagnosis through to treatment. The ability of St Andrew’s Hospital to deliver this care and create the best possible outcomes is crucial to each person’s recovery. Those affected by breast cancer and having undergone treatment at St Andrew’s Hospital are invited to an annual luncheon where guest speakers provide powerful presentations that align with each person’s personal journey post-treatment, providing them the ability to reflect on what bought them here, and how to plan moving forward. A number of exhibitors offering both free and for purchase items or services are available for people to look at, book into or purchase. The highlight of the day is the lingerie fashion parade where women gather the courage to display custom-made lingerie and swimwear, enabling women post-mastectomy to celebrate themselves and not the disease.
Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage — a multicentre subanalysis of the German PBM Network Registry
Authors: Schmitt Elke , Meybohm Patrick , Neef Vanessa , Baumgarten Peter , Bayer Alexandra , Choorapoikayil Suma , Friederich Patrick , Friedrich Jens , Geisen Christof , Güresir Erdem , Grünewald Matthias , Gutjahr Martin , Helmer Philipp , Herrmann Eva , Müller Markus , Narita Diana , Raadts Ansgar , Schwendner Klaus , Seifried Erhard , Stark Patrick , Steinbicker Andrea U. , Thoma Josef , Velten Markus , Weigt Henry , Wiesenack Christoph , Wittmann Maria , Zacharowski Kai , Piekarski Florian ,   German PBM Network Collaborators
Published: February 2022

Purpose

Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period.

Methods

This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH.

Results

A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications.

Conclusions

Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH.

Trial registration

ClinicalTrials.gov, NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795
Synthesis of [7-15N]-GTPs for RNA structure and dynamics by NMR spectroscopy
Authors: Taiwo Kehinde M. , Olenginski Lukasz T. , Nußbaumer Felix , Nam Hyeyeon , Hilber Stefan , Kreutz Christoph , Dayie T. Kwaku
Published: February 2022

Several isotope-labeling strategies have been developed for the study of RNA by nuclear magnetic resonance (NMR) spectroscopy. Here, we report a combined chemical and enzymatic synthesis of [7-15N]-guanosine-5′-triphosphates for incorporation into RNA via T7 RNA polymerase-based in vitro transcription. We showcase the utility of these labels to probe both structure and dynamics in two biologically important RNAs.

Graphical abstract
Improving the microbial sampling and analysis of secondary infected root canals by passive ultrasonic irrigation
Authors: Kluge Milena , Trüschler Johanna , Elamin Fadil , Anderson Annette , Hellwig Elmar , Altenburger Markus , Vach Kirstin , Wittmer Annette , Al-Ahmad Ali
Published: February 2022

Objective

The persistence of pathogenic microorganisms in root canals is the most common reason for the failure of root canal treatment and the necessity of a root filling treatment, which results in an uncertain prognosis due to technical complexity and the variety of highly adaptable microorganisms.

This study evaluated the effect of passive ultrasonic irrigation (PUI) on the outcome of the microbial analysis of root canal-treated teeth with persistent or recurrent apical inflammation in vivo.

Materials and methods

Sample collection was performed after root filling removal (sample S1, control group) and after PUI with NaCl (sample S2) using sterile paper points. In total, 19 samples were obtained. Quantification was performed by means of serial dilution of the samples. Subcultivated pure cultures were identified using MALDI-TOF MS complemented by the Vitek-2-System or PCR, followed by sequencing of the 16S rRNA gene. The results of the samples (S1 and S2) were evaluated regarding their bacterial count and composition.

Results

The total count of bacteria and the number of aerobic/facultative anaerobic microorganisms significantly increased in the S2-samples after application of PUI. The number of obligate anaerobic microorganisms showed an increase after PUI, although it was not significant. We detected 12 different aerobic/facultative anaerobic microorganisms before PUI, and in 21 cases after PUI. Two different obligate anaerobic microorganisms were found in S1 samples compared to nine different species in S2 samples.

Conclusions

PUI is a powerful method for detaching bacteria in infected root canals and enables a more precise analysis of the etiology of persistent endodontic infections.

Clinical relevance

This study indicates that PUI exerts a positive cleansing effect and adds to the accessibility of microorganisms during the application of bactericidal rinsing solution in root canal treatments.
Parameterized verification of systems with component identities, using view abstraction
Authors: Lowe Gavin
Published: February 2022

The parameterized verification problem seeks to verify all members of some collection of systems. We consider the parameterized verification problem applied to systems that are composed of an arbitrary number of component processes, together with some fixed processes. The components are taken from one or more families, each family representing one role in the system; all components within a family are symmetric to one another. Processes communicate via synchronous message passing. In particular, each component process has an identity, which may be included in messages, and passed to third parties. We extend Abdulla et al.’s technique of view abstraction, together with techniques based on symmetry reduction, to this setting. We give an algorithm and implementation that allows such systems to be verified for an arbitrary number of components: we do this for both safety and deadlock-freedom properties. We apply the techniques to a number of examples. We can model both active components, such as threads, and passive components, such as nodes in a linked list: thus our approach allows the verification of unbounded concurrent datatypes operated on by an unbounded number of threads. We show how to combine view abstraction with additional techniques in order to deal with other potentially infinite aspects of the analysis: for example, we deal with potentially infinite specifications, such as a datatype being a queue; and we deal with unbounded types of data stored in a datatype.
Comparison of antimicrobial and wound-healing effects of silver nanoparticle and chlorhexidine mouthwashes: an in vivo study in rabbits
Authors: Moaddabi Amirhossein , Soltani Parisa , Rengo Carlo , Molaei Sahar , Mousavi Seyed Jaber , Mehdizadeh Mojdeh , Spagnuolo Gianrico
Published: February 2022

The objective is to formulate a silver nanoparticle mouthwash and then evaluate its antimicrobial and wound-healing effects in rabbit animal models. Microbial samples were collected from the oral cavity of 60 rabbits. Thereafter, standardized wounds were created in the lateral border of the tongue on the right side for all rabbits. After surgery, digital photographs were obtained from the wounds with standardized settings. To characterize the silver nanoparticles used in the synthetic mouthwash, transmission electron microscopy (TEM) and digital light scattering analysis were used. The animal models were then randomly divided into 4 groups: group 1 received 9.80 wt% silver nanoparticle mouthwash; group 2 received all the ingredients of the formulated mouthwash except for silver nanoparticles; group 3 received chlorhexidine 2.0% mouthwash; and the negative control group did not receive any postoperative mouthwash. Microbial samples were collected from oral cavity of the rabbits each day for four postoperative days. Colony-forming unit (CFU) counts were compared post-operatively with the pre-operative counts. In addition, standardized digital photographs were taken each day from the wounds and the area of the wounds was compared in postoperative and pre-operative images. Data were statistically analyzed using one-way ANOVA and repeated measures variance analysis (α = 0.05). TEM revealed spherical morphology of silver nanoparticles and digital light scattering showed an average size of 5 nm and optimal distribution of the nanoparticles. CFU count significantly decreased in groups 1 and 3 (P < 0.001), while it significantly increased in groups 2 and 4 (P < 0.001). Moreover, a significant difference was observed between the experimental groups (P < 0.001). In addition, wound area decreased significantly in all groups (P < 0.001). However, the difference between wound areas in the groups was not significant, except for the 4th postoperative day (P < 0.001). However, the antibacterial effects and the wound-healing characteristics of the synthetic silver nanoparticle and chlorhexidine mouthwashes were not significantly different (P > 0.05). Silver nanoparticle mouthwash possesses favorable antibacterial and wound-healing effects. The formulated 9.80 wt% silver nanoparticle mouthwash with a particle size of 5 nm can be a promising alternative for application after oral surgical procedures.
Development of 3D Printed Mitral Valve Constructs for Transcatheter Device Modeling of Tissue and Device Deformation
Authors: Vukicevic Marija , Mehta Shail Maharshi , Grande-Allen K. Jane , Little Stephen H.
Published: February 2022

Transcatheter mitral valve repair (TMVR) therapies offer a minimally invasive alternative to surgical mitral valve (MV) repair for patients with prohibitive surgical risks. Pre-procedural planning and associated medical device modeling is primarily performed in silico, which does not account for the physical interactions between the implanted TMVR device and surrounding tissue and may result in poor outcomes. We developed 3D printed tissue mimics for modeling TMVR therapies. Structural properties of the mitral annuli, leaflets, and chordae were replicated from multi-material blends. Uniaxial tensile testing was performed on the resulting composites and their mechanical properties were compared to those of their target native components. Mimics of the MV annulus printed in homogeneous strips approximated the tangent moduli of the native mitral annulus at 2% and 6% strain. Mimics of the valve leaflets printed in layers of different stiffnesses approximated the force–strain and stress–strain behavior of native MV leaflets. Finally, mimics of the chordae printed as reinforced cylinders approximated the force–strain and stress–strain behavior of native chordae. We demonstrated that multi-material 3D printing is a viable approach to the development of tissue phantoms, and that printed patient-specific geometries can approximate the local deformation force which may act upon devices used for TMVR therapies.
Extent and hierarchy of seismic induced inelastic demands in the substructure system of bridges on piled foundation crossing waterways
Authors: Tawadros H. W. S. , Farag M. M. N. , Mehanny S. S. F.
Published: February 2022

The effect of the exposed length of piles supporting bridges crossing waterways on the spread of inelasticity along the pile shaft compared with the extent of plasticity in the body of the column, and hence on the precedence of the formation of plastic hinges in the substructure system is of paramount importance. Plastic hinges may form ideally and preferably at the bottom of the column just above the pile cap, or undesirably either at the pile’s head or at any other section within the pile be it along its free/exposed length immersed in water or its embedded part in soil. A set of bridges are designed according to Eurocode for multiple configurations with various relative stiffness between the column and the group of piles featuring partly exposed shaft. Pushover as well as time history inelastic analyses under a set of ten earthquake records are performed accounting for soil-structure interaction. Results demonstrate that it is likely in some cases characterized by a remarkable increase in the flexural stiffness of the column relative to the group of piles to have spread of inelasticity and plastic hinges forming in piles prior to the column. This is undesirable for a robust, reliable and resilient seismic design as devised by universal design standards for bridges on piled foundation. While there is no clear consensus on the most effective corrective measure to such undesirable response, a few proposed remedial design actions have been formulated in order to preclude (or at least improve the behavior for the case featuring) plastic hinges deplorably forming in the piles prior to the base of the column.
ATGL deficiency aggravates pressure overload-triggered myocardial hypertrophic remodeling associated with the proteasome-PTEN-mTOR-autophagy pathway
Authors: Han Xiao , Zhang Yun-Long , Lin Qiu-Yue , Li Hui-Hua , Guo Shu-Bin
Published: February 2022

Persistent myocardial hypertrophy frequently leads to heart failure (HF). Intramyocardial triacylglycerol (TAG) accumulation is closely related with cardiac remodeling and abnormal contractile function. Adipose triglyceride lipase (ATGL), a key enzyme in TAG metabolism, regulates cardiac function. However, its associated molecular pathways have not been fully defined. Here, cardiac hypertrophy and HF were induced in wild-type (WT) or ATGL knockout (KO) mice through transverse aortic constriction (TAC) for up to 4 weeks. TAC in WT mice significantly reduced cardiac function and autophagy while enhancing left ventricular hypertrophy, interstitial fibrosis, inflammatory response, superoxide generation, and cardiomyocyte apoptosis, accompanied with upregulation of the proteasome activity, reduction of PTEN level and activation of AKT-mTOR signaling, and these effects were further aggravated in ATGL KO mice. Interestingly, ATGL KO-mediated cardiac dysfunction and remodeling were markedly reversed by proteasome inhibitor (epoxomicin) or autophagic activator (rapamycin), but accelerated by PTEN inhibitor (VO-OHpic) or autophagy inhibitor 3-MA. Mechanistically, ATGL KO upregulated proteasome expression and activity, which in turn mediates PTEN degradation leading to activation of AKT-mTOR signaling and inhibition of autophagy, thereby enhancing hypertrophic remodeling and HF. In conclusion, ATGL KO contributes to TAC-induced cardiac dysfunction and adverse remodeling probably associated with the proteasome-PTEN-mTOR-autophagy pathway. Therefore, modulation of this pathway may have a therapeutic effect potential for hypertrophic heart disease.

Graphical abstract

TAC-induced downregulation of ATGL results in increased proteasome (β1i/β2i/β5i) activity, which in turn promotes degradation of PTEN and activation of AKT-mTOR signaling and then inhibits autophagy and ATP production, thereby leading to cardiac hypertrophic remodeling and dysfunction. Conversely, blocking proteasome activity or activating autophagy attenuates these effects.