Effects of medical interventions on health-related quality of life in chronic disease - systematic review and meta-analysis of the 19 most common diagnoses.

Introduction: The demographic shift leads to a tremendous increase in age-related diseases, which are often chronic. Therefore, a focus of chronic disease management should be set on the maintenance or even improvement of the patients' quality of life (QoL). One indicator to objectively measure QoL is the EQ-5D questionnaire, which was validated in a disease- and world region-specific manner. The aim of this study was to conduct a systematic literature review and meta-analysis on the QoL across the most frequent chronic diseases that utilized the EQ-5D and performed a disease-specific meta-analysis for treatment-dependent QoL improvement. Materials and methods: The most common chronic disease in Germany were identified by their ICD-10 codes, followed by a systematic literature review of these ICD-10 codes and the EQ-5D index values. Finally, out of 10,016 independently -screened studies by two persons, 538 studies were included in the systematic review and 216 studies in the meta-analysis, respectively. Results: We found significant medium to large effect sizes of treatment effects, i.e., effect size >0.5, in musculoskeletal conditions with the exception of fractures, for chronic depression and for stroke. The effect size did not differ significantly from zero for breast and lung cancer and were significantly negative for fractures. Conclusion: Our analysis showed a large variation between baseline and post-treatment scores on the EQ-5D health index, depending on the health condition. We found large gains in health-related quality of life mainly for interventions for musculoskeletal disease. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020150936, PROSPERO identifier CRD42020150936.

RNA-seq unravels distinct expression profiles of keloids and Dupuytren's disease.

Keloid scars and Dupuytren's disease are two common, chronic, and incurable fibroproliferative disorders that, among other shared clinical features, may induce joint contractures. We employed bulk RNA sequencing to discern potential shared gene expression patterns and underlying pathological pathways between these two conditions. Our aim was to uncover potential molecular targets that could pave the way for novel therapeutic strategies. Differentially expressed genes (DEGs) were functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein-interaction (PPI) networks were constructed by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The Molecular Complex Detection (MCODE) plugin was used for downstream analysis of the PPI networks. A total of 1922 DEGs were identified within Dupuytren's and keloid samples, yet no overlapping gene expression profiles were detected. Significantly enriched GO terms were related to skin development and tendon formation in keloid scars and Dupuytren's disease, respectively. The PPI network analysis revealed 10 genes and the module analysis provided six protein networks, which might play an integral part in disease development. These genes, including CDH1, ERBB2, CASP3 and RPS27A, may serve as new targets for future research to develop biomarkers and/or therapeutic agents.

Micro-Structural and Biomechanical Evaluation of Bioresorbable and Conventional Bone Cements for Augmentation of the Proximal Femoral Nail.

Osteoporotic proximal femur fractures are on the rise due to demographic change. The most dominant surgical treatment option for per/subtrochanteric fractures is cephalomedullary nailing. As it has been shown to increase primary stability, cement augmentation has become increasingly popular in the treatment of osteoporotic per/subtrochanteric femur fractures. The ultimate goal is to achieve stable osteosynthesis, allowing for rapid full weight-bearing to reduce possible postoperative complications. In recent years, bioresorbable bone cements have been developed and are now mainly used to fill bone voids. The aim of this study was to evaluate the biomechanical stability as well as the micro-structural behaviour of bioresorbable bone cements compared to conventional polymethylmethacrylate (PMMA)-cements in a subtrochanteric femur fracture model. Biomechanical as well as micro-computed tomography morphology analysis revealed no significant differences in both bone cements, as they showed equal mechanical stability and tight interdigitation into the spongious bone of the femoral head. Given the positive risk/benefit ratio for bioresorbable bone cements, their utilisation should be evaluated in future clinical studies, making them a promising alternative to PMMA-bone cements.

One bout of endurance exercise does not change gene expression or proliferation in a C26 colon carcinoma in immunocompetent mice.

PURPOSE: Exercise typically reduces tumour growth, proliferation and improves outcomes. Many of these effects require exercise to change gene expression within a tumour, but whether exercise  actually affects gene expression within a tumour has not been investigated yet. The aim of this study was, therefore, to find out whether one bout of endurance exercise alters gene expression and proliferation in a C26 carcinoma in immunocompetent mice. METHODS: BALB/c were injected with C26 colon carcinoma cells. Once the tumours had formed, the mice either ran for 65 min with increasing intensity or rested before the tumour was dissected. The tumours were then analysed by RNA-Seq and stained for the proliferation marker KI67. RESULTS: One bout of running for 65 min did not systematically change gene expression in C26 carcinomas of BALB/c mice when compared to BALB/c mice that were rested. However, when analysed for sex, the expression of 17, mostly skeletal muscle-related genes was higher in the samples of the female mice taken post-exercise. Further histological analysis showed that this signal likely comes from the presence of muscle fibres from the panniculus carnosus muscle inside the tumours. Also, we found no differences in the positivity for the proliferation marker KI67 in the control and exercise C26 carcinomas. CONCLUSION: A bout of exercise did not systematically affect gene expression or proliferation in C26 carcinomas in immunocompetent BALB/c mice.

Development of a Machine Learning-Based Model to Predict Timed-Up-and-Go Test in Older Adults.

INTRODUCTION: The measurement of physical frailty in elderly patients with orthopedic impairments remains a challenge due to its subjectivity, unreliability, time-consuming nature, and limited applicability to uninjured individuals. Our study aims to address this gap by developing objective, multifactorial machine models that do not rely on mobility data and subsequently validating their predictive capacity concerning the Timed-up-and-Go test (TUG test) in orthogeriatric patients. METHODS: We utilized 67 multifactorial non-mobility parameters in a pre-processing phase, employing six feature selection algorithms. Subsequently, these parameters were used to train four distinct machine learning algorithms, including a generalized linear model, a support vector machine, a random forest algorithm, and an extreme gradient boost algorithm. The primary goal was to predict the time required for the TUG test without relying on mobility data. RESULTS: The random forest algorithm yielded the most accurate estimations of the TUG test time. The best-performing algorithm demonstrated a mean absolute error of 2.7 s, while the worst-performing algorithm exhibited an error of 7.8 s. The methodology used for variable selection appeared to exert minimal influence on the overall performance. It is essential to highlight that all the employed algorithms tended to overestimate the time for quick patients and underestimate it for slower patients. CONCLUSION: Our findings demonstrate the feasibility of predicting the TUG test time using a machine learning model that does not depend on mobility data. This establishes a basis for identifying patients at risk automatically and objectively assessing the physical capacity of currently immobilized patients. Such advancements could significantly contribute to enhancing patient care and treatment planning in orthogeriatric settings.

Systematic review of molecular pathways in burn wound healing.

Depending on extent and depth, burn injuries and resulting scars may be challenging and expensive to treat and above all heavily impact the patients' lives. This systematic review represents the current state of knowledge on molecular pathways activated during burn wound healing. All currently known molecular information about gene expression and molecular interactions in mammals has been summarized. An ample interaction of regenerative cytokines, growth factors, ECM-regenerative molecules and proinflammatory immune response became apparent. We identified three molecules to be most often involved in the pathways: TGFB1, ACTA1 and COL1A1. Yet, other factors including FLII, AKT1 and miR-145 were shown to play pivotal roles in burn wound healing as well. This systematic review helps to explain the fundamental molecular proceedings participating in burn wound healing. A number of new molecular interactions and functional connections were identified yielding intriguing new research targets. An interactive version of the first network about molecular pathways and interactions during burn wound healing is provided in the online edition and on WikiPathways.

The influence of vitamin D on handgrip strength in elderly trauma patients.

BACKGROUND AND OBJECTIVES: The treatment of elderly patients is an increasing challenge and the long-term sequelae often affect activities of daily living and quality of life in those patients. Handgrip strength (HGS) appears as a promising value to predict the outcome after trauma in elderly patients and to assess the overall muscle strength. Besides the possible role of psychological and hormonal factors, vitamin D may have a positive influence. Furthermore, some data suggest that Vitamin D is beneficial regarding muscle strength and possibly prevents further falls and injuries in orthogeriatric patients. The purpose of this study was to identify if Vitamin D is an influencing factor for HGSin elderly trauma patients. MATERIALS AND METHODS: 94 elderly patients in a Level I Trauma Center aged 60 years or older were prospectively enrolled and HGS as well as serum 25-OH Vitamin D concentration (VDC) were measured. In addition, the standardized questionnaires Barthel Index (BI), Parker Mobility Score (PMS), Short Physical Performance Battery (SPPB), Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) and European Quality of Life 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L), were used to record mental health status and demographic data. RESULTS: HGS is mainly related to age and sex in elderly trauma patients. HGS was higher in men (meanmale = 27.31 kg (± 8.11), meanfemale = 15.62 kg (± 5.63), p < 0.001 and decreased with age (ßage = - 0.58, p < 0.001). A significant negative correlation between HGS and VDC exists in the overall sample (ßVDC = - 0.27, pVDC < 0.008), which still remains after adjusting for age (pVDC < 0.004), but is not significant after adjustment for both main confounders, age and sex (pVDC < 0.08). Furthermore, the HGS was lower in pateints who reported frequent falls, stumbling, dizziness or a late onset of menopause, and decreased if patients felt anxious or depressed during measurements (ßanxiety+depression = - 0.26, panxiety+depression < 0.01). CONCLUSIONS: These results do not support the hypothesis that Vitamin D has a positive influence on muscle strength measured by HGS. Nevertheless, this study could confirm the usefulness of HGS as a tool to detect the risk for frequent falls or stumbling. Furthermore, HGS seems to be associated with dizziness and age at onset of menopause. A significant decrease of HGS could also be shown in patients with anxiety and depression. This underlines the importance of interdisciplinary treatment of elderly trauma patients and needs to be taken into account for further studies, as especially the psychological motivation seems to have a significant influence and is sometimes not considered enough in elderly musculo-skeletal patients.

Clinical Acuity in the Emergency Department and Injury Severity Determine Hospital Admission of Older Patients with Low Energy Falls: Outcomes from a Prospective Feasibility Study.

BACKGROUND: Low energy falls (LEF) in older adults constitute a relevant cause for emergency department (ED) visits, hospital admission and in-hospital mortality. Patient-reported outcome measures containing information about patients' medical, mental and social health problems might support disposition and therapy decisions. We investigated the value of a tablet-based (self-)assessment in predicting hospital admission and in-hospital mortality. METHODS: Patients 65 years or older, consecutively presenting with LEF to our level I trauma center ED (from November 2020 to March 2021), were eligible for inclusion in this prospective observational study. The primary endpoint was hospital admission; secondary endpoints were in-hospital mortality and the use of the tablet for self-reported assessment. Multivariate logistic regression models were calculated to measure the association between clinical findings and endpoints. RESULTS: Of 618 eligible patients, 201 patients were included. The median age was 82 years (62.7% women). The hospital admission rate was 45.3% (110/201), with an in-hospital mortality rate of 3.6% (4/110). Polypharmacy (odds ratio (OR): 8.48; 95% confidence interval (95%CI) 1.21-59.37, p = 0.03), lower emergency severity index (ESI) scores (OR: 0.33; 95%CI 0.17-0.64, p = 0.001) and increasing injury severity score (ISS) (OR: 1.54; 95%CI 1.32-1.79, p < 0.001) were associated with hospital admission. The Charlson comorbidity index (CCI) was significantly associated with in-hospital mortality (OR: 2.60; 95%CI: 1.17-5.81, p = 0.03). Increasing age (OR: 0.94; 95%CI: 0.89-0.99, p = 0.03) and frailty (OR: 0.71; 95%CI: 0.51-0.99, p = 0.04) were associated with the incapability of tablet use. CONCLUSIONS: The severity of fall-related injuries and the clinical acuity are easily accessible, relevant predictors for hospital admission. Tablet-based (self-)assessment may be feasible and acceptable during ED visits and might help facilitate comprehensive geriatric assessments during ED stay.

A Review of Biomechanical and Physiological Effects of Using Poles in Sports.

The use of poles in sports, to support propulsion, is an integral and inherent component of some sports disciplines such as skiing (cross-country and roller), Nordic walking, and trail running. The aim of this review is to summarize the current state-of-the-art of literature on multiple influencing factors of poles in terms of biomechanical and physiological effects. We evaluated publications in the subfields of biomechanics, physiology, coordination, and pole properties. Plantar pressure and ground reaction forces decreased with the use of poles in all included studies. The upper body and trunk muscles were more active. The lower body muscles were either less active or no different from walking without poles. The use of poles led to a higher oxygen consumption (VO2) without increasing the level of perceived exertion (RPE). Furthermore, the heart rate (HR) tended to be higher. Longer poles reduced the VO2 and provided a longer thrust phase and greater propulsive impulse. The mass of the poles showed no major influence on VO2, RPE, or HR. Solely the activity of the biceps brachii increased with the pole mass.

Patients With Dupuytren Disease Use Excessive Grip Force When Lifting and Holding Small Objects, Independent of the Degree of Contracture.

OBJECTIVE: To identify the extent and quality of fine motor skill alteration in patients with Dupuytren disease (DD) using an instrumented device measuring grip forces, beyond the commonly used measurement of contracture. DESIGN: Case-control study. SETTING: University outpatient clinic. PARTICIPANTS: Patients with DD (N=27) and a contracture >45° (Tubiana stage II, III, and IV) were included and compared with age-matched healthy control patients (N=27). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES(S): All individuals were subjected to a set of specific tests using a new instrumented device ("manipulandum"). These included lifting, grasping, and then holding the "manipulandum" with 4 different object characteristics (light and heavy weight, rough and smooth surface) along with a measurement of the precision grip strength. Standard measurements including the Nine-Hole Peg Test, a two-point discrimination, and the Disability of Arm, Shoulder and Hand score were evaluated in comparison. RESULTS: Although the measurements of precision grip, two-point discrimination, Nine-Hole Peg Test, and Disability of Arm, Shoulder and Hand score showed no statistically significant differences between both groups, patients with DD applied significantly greater forces when tested with the different subtests using the "manipulandum." Analysis of the 2-phase movement (lifting and holding the "manipulandum") revealed highly significant differences between the groups. CONCLUSIONS: Patients with DD use excessive grip forces when lifting and holding the "manipulandum" when compared with healthy control patients, independent of the degree of contracture. As no differences in precision grip strength were seen, the presented approach is useful to obtain additional important information about fine motor function in diseased hands.

Detailed analysis of surgically treated hand trauma patients in a regional German trauma centre.

Hand and forearm injuries are the most frequent reason for consultations in German emergency departments. Therefore, full recovery has a high social and economic relevance. In this study, data on surgically treated hand injuries in a regional German trauma centre between 01.01.2019 and 31.01.2021 were collected using the new German HandTraumaRegister of the German Society for Hand Surgery. These data were retrospectively analysed and correlated with mobility data of the Bavarian population, the 7-day incidence of Covid-19 infections in Germany and the number of elective hand surgeries. We found that a fall from standing height with consecutive distal radius fracture was the most common injury in women, whereas mechanism of injury and diagnosis were more diverse in men. The populations' mobility correlated well with the number of accidents, which in turn was reciprocal to the 7-day-incidence of Covid-19 infections. The number of elective hand surgeries expectedly dropped significantly during the state-imposed lockdowns. Knowing that mainly young men and elderly women suffer from hand injuries, tailored prevention measures may be elaborated. In order to reduce socioeconomic burden, care for hand injuries and elective hand surgeries must be guaranteed according to the frequency of their occurrence.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model.

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells (ADSPCs) in peripheral nerve recovery. Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs. This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned (2% oxygen for 72 hours) autologous ADSPCs (n = 9). This treatment mode was compared with three others: fibrin conduit seeded with ADSPCs cultivated under normoxic conditions (n = 9); non-cell-carrying conduit (n = 9); and nerve autograft only (n = 9). A 16-week follow-up included functional testing (sciatic functional index and static sciatic index) as well as postmortem muscle mass analyses and morphometric nerve evaluations (histology, g-ratio, axon density, and diameter). At 8 weeks, the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups, indicating faster functional regeneration. Furthermore, histologic evaluation showed significantly increased axon outgrowth/branching, axon density, remyelination, and a reduced relative connective tissue area. Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts. Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

Effect of shape and size of supraspinatus tears on rotator cuff strain distribution: an in vitro study.

BACKGROUND: The impact of the size and shape of a supraspinatus tear on the strain of the intact rotator cuff and the kinematics of the shoulder is still unknown. This, however, can be relevant when deciding whether surgical reconstruction is required to prevent an increase in a tendon defect. In this study, the effect of tear width and shape on rotator cuff strain and glenohumeral kinematics was evaluated during active abduction. METHODS: Twelve fresh-frozen cadaveric shoulders with intact rotator cuffs were used in this study. We created 50% and 100% wide (full-thickness) crescent-shaped (CS) tears (n = 6) and reverse L-shaped (rLS) tears (n = 6) in the supraspinatus tendon and measured strain and kinematics during active humeral elevation until 30°. RESULTS: Both tear shapes and sizes led to an increase in internal rotation, supraspinatus loading force, and superior translation of the humerus. For the 100% wide tear size, anterior translation was observed in the CS tear group, whereas in the rLS tear group, this translation occurred mainly in the posterior direction. Strain was higher in the infraspinatus during the first 25° of abduction in comparison with the supraspinatus tendon in both tear shape groups. An analysis of the anterior and posterior tear borders showed a higher strain concentration on the same side of the tear in the CS tear group with 50% and 100% wide tears. CONCLUSIONS: The influence of different tear shapes on translation in the anterior-posterior direction was evident as both CS and rLS tears led to an oppositely directed translation of the humeral head. The strain analysis showed a stress-shielding effect of the infraspinatus at the beginning of abduction. Therefore, special attention must be paid to correctly identify the tear extension and adequately reconstruct the rotator cuff footprint. Moreover, the constant location of maximum strain in the CS tear group may lead to an earlier progression than in the rLS tear group.

Keloids are transcriptionally distinct from normal and hypertrophic scars.

Wound healing and skin regeneration after injury are complex biological processes, and deep injuries with a high degree of tissue destruction may result in severe scar formation. Clinically, scars can be classified into normal, hypertrophic and keloid scars. However, the molecular signature of each scar type is currently not known. The aim of this study was to reveal the transcriptional landscape of normal, hypertrophic and keloid skin scars following hand and plastic surgery based on total RNA sequencing. Eighteen skin scar samples from hand and plastic surgeries of human donors were minced directly after removal and stored in TRIzol (Thermo Fisher, USA). Samples were then subjected to RNA isolation, cDNA library preparation, bulk RNA sequencing and bioinformatics analysis. We show that keloid scars transcriptionally differed from normal and hypertrophic scars. Normal and hypertrophic scars presented overlapping clustering, and eight genes were shown to be commonly expressed between hypertrophic and normal scars. No genes were specifically expressed at a higher level in keloid and normal scars. Based on gene ontology pathway analysis, genes with a higher level of expression in keloid scars lead to increased (extra-) cellular matrix proliferation and cell interaction. Moreover, tumour-like genes were more highly expressed in keloid scars, supporting the clinical impression of strong and diffuse growth. This study furthers our understanding of the classification of differential scar types based on molecular signature, which may shed light on new diagnostic and therapeutic strategies for keloid scars in the future.

SFRP2 Overexpression Induces an Osteoblast-like Phenotype in Prostate Cancer Cells.

Prostate cancer bone metastasis is still one of the most fatal cancer diagnoses for men. Survival of the circulating prostate tumor cells and their adaptation strategy to survive in the bone niche is the key point to determining metastasis in early cancer stages. The promoter of SFRP2 gene, encoding a WNT signaling modulator, is hypermethylated in many cancer types including prostate cancer. Moreover, SFRP2 can positively regulate osteogenic differentiation in vitro and in vivo. Here, we showed SFRP2 overexpression in the prostate cancer cell line PC3 induces an epithelial mesenchymal transition (EMT), increases the attachment, and modifies the transcriptome towards an osteoblast-like phenotype (osteomimicry) in a collagen 1-dependent manner. Our data reflect a novel molecular mechanism concerning how metastasizing prostate cancer cells might increase their chance to survive within bone tissue.

Quasiclassical approaches to the generalized quantum master equation.

The formalism of the generalized quantum master equation (GQME) is an effective tool to simultaneously increase the accuracy and the efficiency of quasiclassical trajectory methods in the simulation of nonadiabatic quantum dynamics. The GQME expresses correlation functions in terms of a non-Markovian equation of motion, involving memory kernels that are typically fast-decaying and can therefore be computed by short-time quasiclassical trajectories. In this paper, we study the approximate solution of the GQME, obtained by calculating the kernels with two methods: Ehrenfest mean-field theory and spin-mapping. We test the approaches on a range of spin-boson models with increasing energy bias between the two electronic levels and place a particular focus on the long-time limits of the populations. We find that the accuracy of the predictions of the GQME depends strongly on the specific technique used to calculate the kernels. In particular, spin-mapping outperforms Ehrenfest for all the systems studied. The problem of unphysical negative electronic populations affecting spin-mapping is resolved by coupling the method with the master equation. Conversely, Ehrenfest in conjunction with the GQME can predict negative populations, despite the fact that the populations calculated from direct dynamics are positive definite.

Reduced Awareness for Osteoporosis in Hip Fracture Patients Compared to Elderly Patients Undergoing Elective Hip Replacement.

Background: Osteoporotic fractures are associated with a loss of quality of life, but only few patients receive an appropriate therapy. Therefore, the present study aims to investigate the awareness of musculoskeletal patients to participate in osteoporosis assessment and to evaluate whether there are significant differences between acute care patients treated for major fractures of the hip compared to elective patients treated for hip joint replacement.; Methods: From May 2015 to December 2016 patients who were undergoing surgical treatment for proximal femur fracture or total hip replacement due to osteoarthritis and were at risk for an underlying osteoporosis (female > 60 and male > 70 years) were included in the study and asked to complete a questionnaire assessing the awareness for an underlying osteoporosis. ASA Score, FRAX Score, and demographic information have also been examined. Results: In total 268 patients (female = 194 (72.0%)/male = 74 (28%)), mean age 77.7 years (±7.7) undergoing hip surgery were included. Of these, 118 were treated for fracture-related etiology and 150 underwent total hip arthroplasty in an elective care setting. Patients were interviewed about their need for osteoporosis examination during hospitalization. Overall, 76 of 150 patients receiving elective care (50.7%) considered that an examination was necessary, whereas in proximal femur fracture patients the awareness was lower, and the disease osteoporosis was assessed as threatening by significantly fewer newly fractured patients. By comparison, patients undergoing trauma surgery had a considerably greater risk of developing another osteoporotic fracture than patients undergoing elective surgery determined by the FRAX® Score (p ≤ 0.001).; Conclusions: The patients' motivation to endure additional osteoporosis diagnostic testing is notoriously low and needs to be increased. Patients who underwent acute care surgery for a fragility proximal femur fracture, although acutely affected by the potential consequences of underlying osteoporosis, showed lower awareness than the elective comparison population that was also on average 6.1 years younger. Although elective patients were younger and at a lower risk, they seemed to be much more willing to undergo further osteoporosis assessment. In order to better identify and care for patients at risk, interventions such as effective screening, early initiation of osteoporosis therapy in the inpatient setting and a fracture liaison service are important measures.

Early Transcriptional Changes of Adipose-Derived Stem Cells (ADSCs) in Cell Culture.

Background and Objectives: While autologous fat grafting has been carried out in the clinical field for many years, the utilization of isolated and cultured adipose-derived stem cells (ADSCs) is highly restricted in many countries. However, ADSCs are under investigation currently and heavily researched in many cell-based therapy approaches in the field of regenerative medicine. Objective: For the utilization of future cell-based therapies with ADSCs, in vitro cell expansion might be necessary in many cases. Thus, the cellular characteristics of ADSCs may be altered though the process of being cultured. The aim of this study was to assess changes in the gene expression profile of ADSCs after cell expansion for 48 h. Materials and Methods: Isolated ADSCs from five different donors were used for in vitro expansion. For the evaluation of the gene expression profile, mRNA deep Next-Generation Sequencing was performed to evaluate the differences between cultured and freshly isolated cells. Results: Our study gives insight into transcriptional changes in ADSCs after a short cell cultivation period. This includes the most prominent upregulated genes such as PPL, PRR15, CCL11 and ABCA9, as well the most downregulated genes, which are FOSB, FOS, EGR1 and DUSP6. Furthermore, we showed different biological processes that changed during short-term cell expansion, which led to downregulation of fat-associated metabolism hormone processes and to an upregulation of extracellular matrix-associated genes. Conclusion: In conclusion, our study reveals a detailed insight into early changes in the gene expression profile of cultured ADSCs. Our results can be utilized in future experiments.

Fusion of Normoxic- and Hypoxic-Preconditioned Myoblasts Leads to Increased Hypertrophy.

Injuries, high altitude, and endurance exercise lead to hypoxic conditions in skeletal muscle and sometimes to hypoxia-induced local tissue damage. Thus, regenerative myoblasts/satellite cells are exposed to different levels and durations of partial oxygen pressure depending on the spatial distance from the blood vessels. To date, it is unclear how hypoxia affects myoblasts proliferation, differentiation, and particularly fusion with normoxic myoblasts. To study this, we investigated how 21% and 2% oxygen affects C2C12 myoblast morphology, proliferation, and myogenic differentiation and evaluated the fusion of normoxic- or hypoxic-preconditioned C2C12 cells in 21% or 2% oxygen in vitro. Out data show that the long-term hypoxic culture condition does not affect the proliferation of C2C12 cells but leads to rounder cells and reduced myotube formation when compared with myoblasts exposed to normoxia. However, when normoxic- and hypoxic-preconditioned myoblasts were differentiated together, the resultant myotubes were significantly larger than the control myotubes. Whole transcriptome sequencing analysis revealed several novel candidate genes that are differentially regulated during the differentiation under normoxia and hypoxia in mixed culture conditions and may thus be involved in the increase in myotube size. Taken together, oxygen-dependent adaption and interaction of myoblasts may represent a novel approach for the development of innovative therapeutic targets.

An Accurate Linearized Semiclassical Approach for Calculating Cavity-Modified Charge Transfer Rate Constants.

We show that combining the linearized semiclasscial approximation with Fermi's golden rule (FGR) rate theory gives rise to a general-purpose cost-effective and scalable computational framework that can accurately capture the cavity-induced rate enhancement of charge transfer reactions that occurs when the molecular system is placed inside a microcavity. Both partial linearization with respect to the nuclear and photonic degrees of freedom and full linerization with respect to nuclear, photonic, and electronic degrees of freedom (the latter within the mapping Hamiltonian approach) are shown to be highly accurate, provided that the Wigner transforms of the product (WoP) of operators at the initial time is not replaced by the product of their Wigner transforms. We also show that the partial linearization method yields the quantum-mechanically exact cavity-modified FGR rate constant for a model system in which the donor and acceptor potential energy surfaces are harmonic and identical except for a shift in the equilibrium energy and geometry, if WoP is applied.