EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

[Studies on Factors Influencing Influenza Vaccination Rates in Patients with Chronic Obstructive Pulmonary Disease]. / Untersuchungen zu Einflussfaktoren auf die Influenza-Impfraten bei Patienten mit chronisch obstruktiver Lungenerkrankung.

BACKGROUND : With low influenza vaccination rates among the chronically ill, approaches to increase these rates among risk patients with chronic obstructive pulmonary disease (COPD) are to be uncovered. METHODS : 120 COPD patients from Magdeburg filled out a questionnaire and were analyzed regarding the influenza vaccination status 2015/2016 or 2016/2017. Vaccinated and unvaccinated were compared in socio-epidemiological factors, the health belief model (HBM), self-efficacy (GESIS-ASKU), anxiety/depression (HADS-D) and disease processing (FKV-LIS). RESULTS : 62.5 % (n = 75) were vaccinated, 31.7 % (n = 38) unvaccinated, 5.8 % (n = 7) made no statement. In over or equal to 60-year-olds 76 % were vaccinated, in under 60-year-olds 42 % were vaccinated. 60 % (n = 72) knew to belong to a risk group. Unvaccinated indicated greater concern about side effects of the vaccination (p = .004) and drew a worse benefit-expense balance (p = .001). Unvaccinated were more often uncertain about the vaccination protection and the severity of influenza (p ≤ .001). Vaccinated were highly motivated to think about vaccination themselves and more often had a positive vaccination history (p = .001). COPD patients showed a lower self-efficacy than the reference group of the German general population (p = .000), vaccinated and unvaccinated did not differ (p = .418). No difference between vaccinated and unvaccinated was found in the processing of the disease and in depression and anxiety, but unvaccinated tended to give higher anxiety values. CONCLUSION : Measures should particularly target COPD patients under 60 years of age with a negative vaccination history and sensitize them as risk patients. Widespread uncertainties about the severity of influenza and vaccination protection should be addressed. It should be communicated that influenza vaccination does not lead to exacerbation. The vaccination recommendation should increasingly be made by pulmonologists.

Adiponectin stimulates glucose uptake in mouse blastocysts and embryonic carcinoma cells.

Preimplantation embryos are sensitive to maternal hormones affecting embryonic signal transduction and metabolic functions. We examined whether adiponectin, the most abundantly secreted adipokine, can influence glucose transport in mouse embryonic cells. In mouse blastocysts full-length adiponectin stimulated glucose uptake, while no effect of globular adiponectin was found. Full-length adiponectin stimulated translocation of GLUT8 glucose transporter to the cell membrane; we did not detect significant changes in the intracellular localization of GLUT4 glucose transporter in adiponectin-treated blastocysts. To study adiponectin signaling in detail, we used embryoid bodies formed from mouse embryonic carcinoma cell (ECC) line P19. We confirmed the expression of adiponectin receptors in these cells. Similar to mouse blastocysts, full-length adiponectin, but not globular adiponectin, stimulated glucose uptake in ECC P19 embryoid bodies. Moreover, full-length adiponectin stimulated AMPK and p38 MAPK phosphorylation. These results indicate that besides AMPK, p38 MAPK is a potential target of adiponectin in mouse embryonic cells. AMPK inhibitor did not influence the adiponectin-stimulated p38 MAPK phosphorylation, indicating independent action of these two signaling pathways. In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.

PET/CT prior to salvage surgery in recurrent head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival. RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

The clinical utility of FDG PET/CT among solid organ transplant recipients suspected of malignancy or infection.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015. METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined. RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively. CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.

Potential of the polymer poly-[2-(tert-butylamino) methylstyrene] as antimicrobial packaging material for meat products.

AIMS: The objective of the study was to investigate the antimicrobial potential of a new SAM(®) polymer poly(TBAMS) as packaging material for meat products. METHODS AND RESULTS: The influence of temperature, time and product factors on the antimicrobial activity of poly(TBAMS) against different bacteria was determined using a modified test method based on the Japanese Industrial Standard 2801:2000. Results showed a significant reduction in bacterial counts on poly(TBAMS) compared with the reference material of several meat-specific micro-organisms after 24 h at 7°C. Bacterial counts of Staphylococcus aureus, Listeria monocytogenes, Lactobacillus spp., Brochothrix thermosphacta and Escherichia coli were reduced by >4·0 log10  units. Pseudomonas fluorescens was less sensitive to poly(TBAMS) within 24 h between 2 and 7°C. Prolonging the storage time to 48 h, however, resulted in an increased reduction rate. Furthermore, antimicrobial activity was also observed if meat components in the form of meat extract, meat juice or bovine serum albumin protein were present. Antimicrobial activity was also achieved if inoculated with mixed cultures. CONCLUSIONS: Poly(TBAMS) showed antimicrobial properties under conditions typical for meat supply chains. SIGNIFICANCE AND IMPACT OF THE STUDY: Poly(TBAMS) bears a high potential to increase safety and shelf life of meat products.

Colloidal crystallite suspensions studied by high pressure small angle x-ray scattering.

We report on high pressure small angle x-ray scattering on suspensions of colloidal crystallites in water. The crystallites made out of charge-stabilized poly-acrylate particles exhibit a complex pressure dependence which is based on the specific pressure properties of the suspending medium water. The dominant effect is a compression of the crystallites caused by the compression of the water. In addition, we find indications that also the electrostatic properties of the system, i.e. the particle charge and the dissociation of ions, might play a role for the pressure dependence of the samples. The data further suggest that crystallites in a metastable state induced by shear-induced melting can relax to a similar structural state upon the application of pressure and dilution with water. X-ray cross correlation analysis of the two-dimensional scattering patterns indicates a pressure-dependent increase of the orientational order of the crystallites correlated with growth of these in the suspension. This study underlines the potential of pressure as a very relevant parameter to understand colloidal crystallite systems in aqueous suspension.

Requirements and Application Guide for the Use of Quality Indicators in Medical Care: Results of a Systematic Review.

Background: Quality indicators are employed in the assessment of quality of medical care. Valid measurement and reporting of quality are essential for maintenance and enhancement of high-quality medical care. The aim of this study was to identify the requirements for quality indicators and their successful implementation in routine care. Method: A systematic literature search conducted in Medline using MESH keywords resulted in 573 hits. A complementary hand search additionally identified 153 papers, so that in all 726 abstracts were screened. In conformity with the PRISMA Statement, 83 papers were finally included in this review. Results: Quality criteria are described in 48 publications and requirements for the application of quality indicators in medical care are given in 41 publications. Validity (n=19), feasibility (n=16), reliability (n=15), and interpretability of the quality indicator (n=14) are the most frequently named quality criteria, followed by relevance (n=10), sensitivity (n=8) and risk adjustment (n=6). The most common requirements for the application of quality indicators are integration of quality indicators in the given healthcare setting (n=15) and ability to derive potential improvement (n=11), data validity (n=8), data availability (n=7) as well as acceptance of the measurement in the given setting (n=6). Conclusion: Plausible quality measurements help improve healthcare structures and processes and provide patients and professionals with valid statements on the quality of care. The original articles examined focus primarily on the validity of quality indicators. A consensus on methodological criteria for the development, implementation and application of quality indicators is required. Furthermore, the practical applicability of quality criteria should be tested empirically.

Strong and parallel salinity-induced phenotypic plasticity in one generation of threespine stickleback.

Phenotypic plasticity is a major factor contributing to variation of organisms in nature, yet its evolutionary significance is insufficiently understood. One example system where plasticity might have played an important role in an adaptive radiation is the threespine stickleback (Gasterosteus aculeatus), a fish that has diversified after invading freshwater lakes repeatedly from the marine habitat. The parallel phenotypic changes that occurred in this radiation were extremely rapid. This study evaluates phenotypic plasticity in stickleback body shape in response to salinity in fish stemming from a wild freshwater population. Using a split-clutch design, we detected surprisingly large phenotypically plastic changes in body shape after one generation. Fish raised in salt water developed shallower bodies and longer jaws, and these changes were consistent and parallel across families. Although this work highlights the effect of phenotypic plasticity, we also find indications that constraints may play a role in biasing the direction of possible phenotypic change. The slopes of the allometric relationship of individual linear traits did not change across treatments, indicating that plastic change does not affect the covariation of traits with overall size. We conclude that stickleback have a large capacity for plastic phenotypic change in response to salinity and that plasticity and evolutionary constraints have likely contributed to the phenotypic diversification of these fish.

Effects of equal-volume resistance training performed one or two times a week in upper body muscle size and strength of untrained young men.

AIM: The purpose of the present study was to compare the effects of equal-volume resistance training (RT) performed once or twice a week on muscle mass and strength of the elbow flexors in untrained young men. METHODS: Thirty men (23 ± 3 years) without previous resistance training experience were divided into two groups: Group 1 (G1) trained each muscle group only once a week and group 2 (G2) trained each muscle twice a week during 10 weeks. Baseline and 10 weeks post-test elbow flexors muscle thickness (MT) were measured using a B-Mode ultrasound. Peak torque (PT) was assessed by an isokinetic dynamometer before and after the training program. RESULTS: Elbow flexors MT increased significantly (P<0.05) from 31.70 ± 3.31 to 33.43 ± 3.46 mm in G1, and from 32.78 ± 4.03 to 35.09 ± 3.55 mm in G2. Elbow flexors PT also increased (P<0.05) from 50.77 ± 9.26 to 54.15 ± 10.79 N.m in G1, and from 48.99 ± 11.52 to 55.29 ± 10.24 N.m in G2. The results of ANOVA did not reveal group by time interactions for any variable, indicating no difference between groups for the changes in MT or PT. CONCLUSION: The results from the present study suggest that untrained men experience similar gains in muscle mass and strength with equal volume RT performed one or two days per week.

[Medial femoral neck fractures: possible reasons for delayed surgery. Part 2: Results of data from external inpatient quality assurance within the framework of secondary data evaluation]. / Mediale Schenkelhalsfraktur: mögliche Gründe für eine verzögerte operative Versorgung. Teil 2: Ergebnisse der Daten der externen stationären Qualitätssicherung im Rahmen sekundärer Datennutzung.

PROBLEM: In Germany a disproportionate number of patients with a femoral neck fracture still experience a delay in surgery. In 2008 delays of more than 48 h after admission occurred for 15.4 % of patients. This leads to increases in surgical and general complications as well as pressure sores. OBJECTIVE: Possible reasons that lead to delayed operations were investigated in a nationwide study. DATA AND METHODS: Using nationwide data from the German inpatient external quality assurance program from the year 2008 the reasons for performing operations later than 48 h after hospital admission were examined both exploratory and analytically using a multiple logistic regression model considering combined effects. RESULTS: Surgery was more frequently delayed for patients who were admitted to hospital on Friday or Saturday, patients with a higher American Society of Anesthesiologists (ASA) classification, men, patients with malignant diseases, in the presence of infectious diseases and patients with heart disease. Operations carried out within the first 48 h were more frequent with displaced fractures and in the presence of hypertension or mental illness. The volume per hospital had no consistent effect on the time delay of surgery. During the week no significant differences between the departments were detected. On Friday or Saturday surgery was delayed more often when patients were admitted to a department of general surgery than to a department of trauma surgery or orthopedics. CONCLUSIONS: There are medical and non-medical reasons for delayed surgery of femoral neck fractures. Studies have confirmed that delayed surgery for femoral neck fracture harms the patients. Organizational reasons which prevent an immediate operation, e.g. admission on Friday or Saturday, should therefore be eliminated by improvements in hospital organization and staffing. These can be measures of individual hospitals or of several hospitals in cooperation. The target should be to ensure a comprehensive and timely provision of the highest quality care even at the weekend.

Single shot speckle and coherence analysis of the hard X-ray free electron laser LCLS.

The single shot based coherence properties of hard x-ray pulses from the Linac Coherent Light Source (LCLS) were measured by analyzing coherent diffraction patterns from nano-particles and gold nanopowder. The intensity histogram of the small angle x-ray scattering ring from nano-particles reveals the fully transversely coherent nature of the LCLS beam with a number of transverse mode 〈Ms〉 = 1.1. On the other hand, the speckle contrasts measured at a large wavevector yields information about the longitudinal coherence of the LCLS radiation after a silicon (111) monochromator. The quantitative agreement between our data and the simulation confirms a mean coherence time of 2.2 fs and a x-ray pulse duration of 29 fs. Finally the observed reduction of the speckle contrast generated by x-rays with pulse duration longer than 30 fs indicates ultrafast dynamics taking place at an atomic length scale prior to the permanent sample damage.

Non-equilibrium coherence dynamics in one-dimensional Bose gases.

Low-dimensional systems provide beautiful examples of many-body quantum physics. For one-dimensional (1D) systems, the Luttinger liquid approach provides insight into universal properties. Much is known of the equilibrium state, both in the weakly and strongly interacting regimes. However, it remains a challenge to probe the dynamics by which this equilibrium state is reached. Here we present a direct experimental study of the coherence dynamics in both isolated and coupled degenerate 1D Bose gases. Dynamic splitting is used to create two 1D systems in a phase coherent state. The time evolution of the coherence is revealed through local phase shifts of the subsequently observed interference patterns. Completely isolated 1D Bose gases are observed to exhibit universal sub-exponential coherence decay, in excellent agreement with recent predictions. For two coupled 1D Bose gases, the coherence factor is observed to approach a non-zero equilibrium value, as predicted by a Bogoliubov approach. This coupled-system decay to finite coherence is the matter wave equivalent of phase-locking two lasers by injection. The non-equilibrium dynamics of superfluids has an important role in a wide range of physical systems, such as superconductors, quantum Hall systems, superfluid helium and spin systems. Our experiments studying coherence dynamics show that 1D Bose gases are ideally suited for investigating this class of phenomena.

[Development and first results of fast and cost-effective examination methods for an ophthalmological screening within the National Cohort]. / Entwicklung und erste Anwendungserfahrungen einer schnellen und kostengünstigen ophthalmologischen Untersuchung für die Nationale Kohorte.

BACKGROUND: For an implemented ophthalmological screening within a German long-term cohort study (National Cohort) simple and effective methods for an examination of visual acuity and for non-mydriatic retina photografies should be evaluated. Furthermore standard operating-procedures (SOP) should be developed. METHODS: In the years 2011 and 2012 pinhole visual acuity measurements and automated retina photographies (DRS, CenterVue S. p. a., Padua, Italy) were made at three different epidemiological study centers within Germany. Furthermore, anterior segment images were taken by the camera. Standard operating procedures (SOP) regarding the ophthalmological screening were developed and evaluated within the study. The main question was whether it is possible to implement the screening methods within the National Cohort. Further main outcomes were quality and interpretability of the taken images. RESULTS: 457 subjects (914 eyes) were examined within the investigation. Median VA was 0.8 for right and left eyes (p > 0.42). Image quality of the photographies was good in 491 cases (54 %), fair in 239 cases (26 %) and bad in 179 cases (20 %). The usability of the images was without limitations in 686 cases (75 %), limited in 152 cases (17 %) and not given in 71 cases (8 %). Increasing age of the subjects was slightly correlated with decreasing image quality (r = 0.26) and decreasing image usability (r = 0.2). Anterior segment photographies were usable in 176 eyes (56 %). CONCLUSION: The developed screening method fulfilled the specifications of the National Cohort. The used pinhole visual acuity examination was fast and cheap. Image quality and usability of the retina photographies could be improved with prolonged pupil recovery times. The quality of the anterior segment images could not fulfill the expectations and were taken out of the further examinations of the ophthalmological screening. The written SOP showed good acceptance within the investigators' daily routine. The ophthalmological screening within the National Cohort generates information (e. g., pathologies of the vessels or of the retina) which are useful not only from an ophthalmological point of view.

The effects of force application on the compressive properties of femoral spongious bone.

BACKGROUND: End artefacts play a major role in uniaxial compression tests with cancellous bone specimens. They lead to misinterpretation of mechanical parameters of bones due to uncontrolled introduction of bending moments into the free ends of trabeculae. This work aims to simplify current methods preventing end-artefacts and furthermore to investigate the influence of end artefacts on plateau stress. METHODS: 176 cylindrical cancellous bone specimens were taken from human femoral condyles and tested in uniaxial compression. The specimens were divided into 2 groups (direct, end-cap) and compressive modulus, maximum stress, plateau stress, energy absorbtion as well as apparent density were evaluated. Density values are from separate specimens which are immediately adjacent to the mechanical specimen. FINDINGS: All mechanical parameters were significantly higher in the end-cap specimens than in the direct ones by about 30 - 40 %, thus reaching similar differences as the previous studies. Greatest differences between groups were determined for compressive modulus (45 %) and plateau stress (35 %). Energy absorbtion can be explained with great accuracy by plateau stress (P < 0.001; R2 = 0.95). Among all parameters plateau stress can be best explained by apparent density using an exponential function (P < 0.001; R2 = 0.38). INTERPRETATION: The end-cap method used here to prevent end artefacts showed variations consistent with the literature when compared to the direct method. Additionally it was shown that the way in which the force is applied to the specimen has a major influence on the failure progression behavior, which was characterized using the plateau stress.

A highly versatile biopolymer-based platform for the maturation of human pluripotent stem cell-derived cardiomyocytes enables functional analysis in vitro and 3D printing of heart patches.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent a valuable tool for in vitro modeling of the cardiac niche and possess great potential in tissue engineering applications. However, conventional polystyrene-based cell culture substrates have adverse effects on cardiomyocytes in vitro due to the stress applied by a stiff substrate on contractile cells. Ultra-high viscosity alginates offer a unique versatility as tunable substrates for cardiac cell cultures due to their biocompatibility, flexible biofunctionalization, and stability. In this work, we analyzed the effect of alginate substrates on hPSC-CM maturity and functionality. Alginate substrates in high-throughput compatible culture formats fostered a more mature gene expression and enabled the simultaneous assessment of chronotropic and inotropic effects upon beta-adrenergic stimulation. Furthermore, we produced 3D-printed alginate scaffolds with differing mechanical properties and plated hPSC-CMs on the surface of these to create Heart Patches for tissue engineering applications. These exhibited synchronous macro-contractions in concert with more mature gene expression patterns and extensive intracellular alignment of sarcomeric structures. In conclusion, the combination of biofunctionalized alginates and human cardiomyocytes represents a valuable tool for both in vitro modeling and regenerative medicine, due to its beneficial effects on cardiomyocyte physiology, the possibility to analyze cardiac contractility, and its applicability as Heart Patches.

There is an obstetrical dilemma: Misconceptions about the evolution of human childbirth and pelvic form.

Compared to other primates, modern humans face high rates of maternal and neonatal morbidity and mortality during childbirth. Since the early 20th century, this "difficulty" of human parturition has prompted numerous evolutionary explanations, typically assuming antagonistic selective forces acting on maternal and fetal traits, which has been termed the "obstetrical dilemma." Recently, there has been a growing tendency among some anthropologists to question the difficulty of human childbirth and its evolutionary origin in an antagonistic selective regime. Partly, this stems from the motivation to combat increasing pathologization and overmedicalization of childbirth in industrialized countries. Some authors have argued that there is no obstetrical dilemma at all, and that the difficulty of childbirth mainly results from modern lifestyles and inappropriate and patriarchal obstetric practices. The failure of some studies to identify biomechanical and metabolic constraints on pelvic dimensions is sometimes interpreted as empirical support for discarding an obstetrical dilemma. Here we explain why these points are important but do not invalidate evolutionary explanations of human childbirth. We present robust empirical evidence and solid evolutionary theory supporting an obstetrical dilemma, yet one that is much more complex than originally conceived in the 20th century. We argue that evolutionary research does not hinder appropriate midwifery and obstetric care, nor does it promote negative views of female bodies. Understanding the evolutionary entanglement of biological and sociocultural factors underlying human childbirth can help us to understand individual variation in the risk factors of obstructed labor, and thus can contribute to more individualized maternal care.