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Research question Does complete resection of endometriosis improve embryo quality as assessed by morphokinetic parameters using time-lapse microscopy? Design For this retrospective study we analysed 237 fertilised, cultured and transferred embryos from 128 fresh IVF and/ or ICSI transfer cycles. Endometriosis was confirmed or excluded by laparoscopy. Patients were stimulated with recombinant FSH using GnRH agonist and antagonist protocols. After fertilisation, a time-lapse incubation system was used for observation. Embryo quality was assessed using the KIDScore™ D3 and D5 implantation data algorithm. Results The analysis showed a median KIDScore™ D5 of 2.6 (on a scale of 1 to 9.9) for embryos from patients with endometriosis without complete resection. The control group without endometriosis achieved a score of 6.8 (p = 0.003). The median score for embryos from endometriosis patients with complete resection was 7.2, which was a significant increase compared to embryos from patients without complete resection (p = 0.002). We observed an effect size of r = 0.4 for complete resection versus no resection of endometriosis using the KIDScore™ D5. There were no differences in KIDScore™ D3 between the three patient groups. Pregnancy and miscarriage rates showed the same clinical trends. In three of our four case series of patients who underwent IVF/ ICSI cycles before and after complete resection, we found a marked improvement in embryo quality after complete resection. Conclusions Complete resection of endometriosis could significantly improve the otherwise poor embryo quality of patients undergoing IVF-procedures. The data, therefore, strongly support recommending surgery to patients with endometriosis prior to assisted reproduction.

In addition to the well-known threats of bird and hail strikes, small unmanned aerial vehicles (sUAV) pose a new threat to manned aviation. Determining the severity of collisions between sUAVs and aircraft structures is essential for the safe use and integration of drones in airspace. A generic analytical calculation model needs to be developed to supplement the existing test and simulation data. This paper presents an analytic model for drone collisions with perpendicular and inclined targets. The targets have a rigid or elastic material behavior. The aircraft impact model, which is used for the design of nuclear reactor structures, is transferred and adjusted for sUAV impacts to calculate the impact force. A mass- and a burst load distribution are needed as input parameters. Both distributions are determined for an sUAV design depending on the flight direction. Compared to previous calculations, the new approach is to consider a moving target structure, which produces more realistic results. We compare the calculation results with simulation data from sUAV collisions with a commercial airliner windshield from the literature. The calculations show plausible results and a good agreement with literature data. Subsequently, the influence of the input parameters on the impact force is investigated. We see that spring stiffness, target mass, burst load distribution and damping have minor influence on the overall impact force. The impact velocity, mass distribution and flight orientation on the other hand have a major influence on the impact force. Further tests are needed to validate the impact model.

Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.

Background: Several classification systems based on arthroscopy have been used to describe lesions of the ligamentum teres (LT) in young active patients undergoing hip-preserving surgery. Inspection of the LT and associated lesions of the adjuvant fovea capitis and acetabular fossa is limited when done arthroscopically but is much more thorough during open surgical hip dislocation. Therefore, we propose a novel grading system based on our findings during surgical dislocation comprising the full spectrum of ligamentous-fossa-foveolar complex (LFFC) lesions. Purpose: To determine (1) intraobserver reliability and (2) interobserver reproducibility of our new grading system. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: We performed this validation study on 211 hips (633 images in total) with surgical hip dislocation (2013-2021). We randomly selected 5 images per grade for each LFFC item to achieve an equal representation of all grades (resulting in 75 images). The ligament, fossa, and fovea were subcategorized into normal, inflammation, degeneration, partial, and complete defects. All surgeries were performed in a standardized way by a single surgeon. The femur was disarticulated using a bone hook, the LT was inspected, documented and resected, then the fossa and fovea were documented with the femoral head in full dislocation using a 70° arthroscope. Six observers with different levels of expertise in hip-preserving surgery independently conducted the measurements twice, and intraclass correlation coefficients (ICC) were calculated to determine (1) intraobserver reliability and (2) interobserver reproducibility of the novel grading system. Results: For intraobserver reliability, excellent ICCs were found in both the junior and the experienced raters for grading the ligament, fossa, fovea, and total LFFC (ICCs ranged from 0.91 to 0.99 for the LFFC score). We found excellent interobserver reproducibility between raters for all items of the LFFC (all interobserver ICCs ≥ 0.76). Conclusion: Our new grading system for lesions of the LFFC is highly reliable and reproducible. It covers the full spectrum of damage more precisely than arthroscopic classifications do and offers a scientific basis for standardized intraoperative evaluation.

Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14+CD16+). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.

FATWO (female adnexal tumour of probable Wolffian origin) denotes a rare tumour of the female adnexa which has been described in nearly 80 cases worldwide and which presumably originates in the remains of the Wolffian ducts. In 10 to 20 percent of patients, a metastasis or recurrence was seen subsequently and for this reason, a malignant potential is attributed to the FATWO. Because of the small number of cases, there is no clear therapeutic recommendation. The method of choice currently is surgical treatment with hysterectomy and adnexectomy. The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. This work provides an overview of the literature on epidemiology, imaging and histopathological diagnostic features as well as therapeutic options of this same tumour form.FATWO (female adnexal tumour of propable Wolffian origin) bezeichnet einen seltenen Tumor der weiblichen Adnexe, der weltweit in knapp 80 Fällen beschrieben wurde und dessen Ursprung vermutlich in den Residuen der Wolffʼschen Gänge liegt. Bei 10 bis 20 Prozent der Patientinnen zeigte sich im Verlauf eine Metastasierung oder ein Rezidiv, weshalb dem FATWO ein malignes Potenzial zugeschrieben wird. Aufgrund der kleinen Fallzahl existiert keine klare Therapieempfehlung. Methode der Wahl ist derzeit eine operative Sanierung mit Hysterektomie und Adnexektomie. Der Nutzen von Radio- und Chemotherapien ist nicht eindeutig, vereinzelt wurden Therapieversuche mit Imatinib bei CD117-Positivität oder Therapieversuche auf endokriner Basis unternommen. Diese Arbeit zeigt eine Literaturübersicht über Epidemiologie, bildgebende und histopathologische Diagnosemerkmale sowie Therapieoptionen dieser seltenen Tumorform.

Elderly care facilities have become a major focus of coronavirus disease (COVID-19) control. Here, we describe an outbreak of COVID-19 in a nursing home in Germany from 8 March to 4 May 2020 (58 days), and the effect of an intervention of general screening and cohort isolation. COVID-19 cases among residents and staff were recorded on a daily basis from the first positive SARS-CoV-2 test from a resident on 8 March 2020, until 4 May 2020 when the last staff member was classified COVID-19 negative. Eighty of 160 residents (50%) and 37 of 135 staff members (27%) tested positive for SARS-CoV-2. Twenty-seven of the 80 residents were asymptomatic but tested positive during the first general screening. Cohort isolation of SARS-CoV-2 positive residents by reorganising the facility proved to be a major effort. After the intervention, four further asymptomatic residents tested positive in follow-up screenings within a period of 6 days, and were possibly infected prior to the intervention. Thereafter, no further infections were recorded among residents. The described outbreak was controlled by implementing general screening and rigorous cohort isolation, providing a blueprint for similar facilities.

BackgroundHypertension is a major risk factor for cardiovascular disease and the leading cause of premature deaths in the United States. Hypertension is a commonly reported chronic disease in foreign-born-adult immigrants living in the United States, and psychosocial-cultural factors such as lack of health insurance and poor transportation services have been reported particularly among foreign-born immigrant women with hypertension and other chronic diseases. However, little is known about the socio-cultural factors that influence access to and utilization of hypertension health services in West-African-born immigrant women in the United States.MethodsThis study utilized a qualitative design with a phenomenological approach to interview a purposeful sample of fifteen West-African-born immigrant women that reported diagnosis of hypertension (12 with health insurance and 3 without health insurance) in the Washington District of Columbia Metropolitan area. The Patient Centered Access to Health Care Model guided the conceptual framework of the study. Thematic analysis was used to identify patterns and generate categories and themes.ResultsFive themes emerged from the analysis: Health Insurance Coverage, Frequency of Hypertension Care Visits, Interaction with HCP, Culturally Sensitive HCP, and HTN Self-Care Incentives. Eighty percent of participants had medical insurance and transportation services, but delayed seeking HTN care because their health care providers did not listen to their concerns or discuss their preferences before prescribing treatment. More than 60 percent of the women reported that clinicians did not listen to their concerns or provide culturally appropriate guidance during their visits.ConclusionsThese findings could be helpful for larger scale studies, or smaller comparative studies in other regions of the United States. Cultural competence training should be included in the continuing education curriculum of healthcare providers serving the West-African-born immigrant population.

Objective Hyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity. Methods Blood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing. Results Short-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity. Conclusions Gut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.

Zusammenfassung Hintergrund Beratung durch Ärzte in Bezug auf Lebensstil im Allgemeinen und das Bewegungsverhalten im Speziellen steht seit dem Inkrafttreten des Präventionsgesetzes in Deutschland wieder vermehrt im Fokus. Auch für die Bewegungstherapie spielt die Anknüpfung an ärztliche Beratung eine wichtige Rolle. Die Erwartungen an ärztliche Beratung sind dabei durchaus hoch, wohingegen es eine Vielzahl an Barrieren zu geben scheint. In einem Projekt (PATEN im Rahmen vom Forschungsverbund Capital4Health) zur Bewegungsförderung im Seniorenwohnstift wurde ein Informations- bzw. Schulungsangebot erprobt. Dabei wurden Praxishilfen entwickelt, die es Ärzten erleichtern sollen, das Thema Bewegung im zeitlich begrenzten Rahmen strukturiert anzusprechen. Konzeption Die beiden Praxishilfen (Tischvorlagen) beinhalten ein potenzielles Ablaufschema für eine Kurzberatung nach den so genannten 5 A‘s sowie eine grafische Darstellung von gängigen Bewegungsempfehlungen für Ältere. Letztere beziehen sich vornehmlich auf die deutschen Nationalen Empfehlungen für Bewegung und Bewegungsförderung. Die 5A-Methode (Ask / Assess, Agree, Advise, Assist, Arrange) ist evidenzbasiert, eignet sich für die primäre Gesundheitsversorgung und wird von gängigen Leitlinien empfohlen. Diskussion Interventionen zur Bewegungsförderung in der Arztpraxis können von unterschiedlichster Dauer und inhaltlicher Ausrichtung sein. Die vorliegenden Praxishilfen können zur flexiblen Umsetzung genutzt werden. Sie sind dabei auch von Bewegungsfachleuten und evtl. anderen Berufsgruppen einsetzbar.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

Introduction: Expression of fibroblast activation protein (FAP) has been detected in activated fibroblasts participating in injury response, fibrotic and inflammatory conditions, and tumorigenesis. Human endometrium is equally characterized by rapid tissue remodeling events due to the reproductive tasks comprising the activity of proteolytic enzymes. Objective: We therefore hypothesized that FAP-positive fibroblasts could also be involved in physiological processes requiring tissue remodeling, such as decidualization during early pregnancy. Methods/Results: The expression of FAP was analyzed by immunohistochemistry in frozen sections of decidual tissue from early pregnancy (gestational weeks: 6–12). All tissue samples clearly displayed a strong expression of FAP on the surface of stromal fibroblasts. Additionally, the percentage of FAP-positive fibroblasts freshly isolated from the decidua of the corresponding gestational weeks was calculated by applying FACS analysis. Decidual fibroblasts of different gestational weeks showed a significant decrease in FAP expression between the 6th and 7th weeks of gestation, which was followed by a steady slow reconstitution. By analyzing the expression of cytokines, chemokines, and growth factors of isolated FAP-positive decidual fibroblasts, we detected high levels of monocyte-attracting chemokines (growth-related oncogene alpha and monocyte chemoattractant protein-1 and -2), granulocyte-attracting chemokines (e.g., IL-8), proinflammatory factors (IL-1α and tumor necrosis factor alpha), and angiogenic substances (e.g., vascular endothelial growth factor and IL-8), which all promote an optimal microenvironment for implantation and growth of the conceptus. Conclusions: Our data demonstrate that the healthy early pregnancy decidua is characterized by a general occurrence of FAP-positive fibroblasts possibly participating in active tissue remodeling during implantation.

Src homology region 2 domain-containing phosphatase-1 (Shp1) plays an important role in modulating insulin signaling and thereby glucose homeostasis. Our laboratory has demonstrated that despite being more prone to hepatic steatosis, mice with a liver specific Shp1 knock out (Shp1H-KO) on high-fat diet (HFD) exhibit improved fasting glycaemia, reduced insulin resistance and lower inflammation than their flox/flox littermates. Microarray analysis of HFD-fed Shp1H-KO versus Shp1fl/fl livers revealed elevated levels of peroxisome proliferator-activated receptor gamma (PPARγ), an important transcription factor controlling adipogenesis. In addition, overexpression of Shp1 decreased PPARγ activity in vitro. The aim of this study was to investigate the mechanism of regulation of PPARγ by Shp1. Molecular modeling analyses suggested that Shp1 interaction with PPARγ depends on the tyrosine phosphorylation status of PPARγ. We found, by co-immunoprecipitation, that Shp1 N-terminal SH2-domains binds to PPARγ. We confirmed PPARγ tyrosine-phosphorylation and demonstrated that this phosphorylation could be reduced by Shp1 in vitro. Using mass spectrometry, we identified 5 phosphorylated tyrosine residues in PPARγ. Mutagenesis experiments showed that PPARγ significantly lost its activity when two of these sites were selectively and independently mutated to the non-phosphorylatable phenylalanine but did not interfere with the nuclear localization of PPARγ. Additionally, we generated Shp1 knockout HepG2 cells using CRISPR-Cas9 technology. We found that expression of several PPARγ regulated transcripts was upregulated in Shp1-KO cells as compared to control cells. Altogether, we show that PPARγ is a novel substrate of Shp1. Our results reveal a fine regulation of PPARγ tyrosine phosphorylation by Shp1, which might lead to novel therapeutic approaches for treating metabolic disorders related to obesity. Disclosure A. Kumar: None. M. Lavallee-Bourget: None. M. Forest: None. M. Schwab: None. K. Bellmann: None. V. Houde: None. H. Maaroufi: None. N. Beauchemin: None. A. Marette: Advisory Panel; Self; Plexus, Valbiotis. Consultant; Self; Danone Nutricia Research.

Quorum quenching lactonases are enzymes capable of hydrolyzing lactones, including N-acyl homoserine lactones (AHLs). AHLs are molecules known as signals in bacterial communication dubbed quorum sensing. Bacterial signal disruption by lactonases was previously reported to inhibit behavior regulated by quorum sensing, such as the expression of virulence factors and the formation of biofilms. Herein, we report the enzymatic and structural characterization of a novel lactonase representative from the metallo-β-lactamase superfamily, dubbed GcL. GcL is a broad spectrum and highly proficient lactonase, with kcat /KM values in the range of 104 to 106 m-1 s-1 . Analysis of free GcL structures and in complex with AHL substrates of different acyl chain length, namely, C4-AHL and 3-oxo-C12-AHL, allowed their respective binding modes to be elucidated. Structures reveal three subsites in the binding crevice: 1) the small subsite where chemistry is performed on the lactone ring; 2) a hydrophobic ring that accommodates the amide group of AHLs and small acyl chains; and 3) the outer, hydrophilic subsite that extends to the protein surface. Unexpectedly, the absence of structural accommodation for long substrate acyl chains seems to relate to the broad substrate specificity of the enzyme.

It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc.

Diel (also called diurnal) discharge patterns with minima in the afternoon are generally explained by the daily cycle of evapotranspiration, while maxima in the afternoon are often linked to freeze-thaw cycles. In a schistose and forested headwater catchment in Luxembourg, we observed daily discharge maxima in the afternoon, although temperatures remained persistently above zero and vegetation was still in a dormant state. We show that diel water temperature fluctuations - and therefore viscosity fluctuations - in the upper layer of the riparian zone can be an explanation for the observed daily discharge maxima in the afternoon during the dormant season. In the transition period between the dormant and the growing season, the counteracting viscosity and evapotranspiration processes cancel each other out. Subsequently, during the growing season, evapotranspiration is the dominant process guiding the diel discharge pattern; nevertheless, the viscosity effect might still be present, but invisible. We believe this finding also to be of relevance when analyzing daily fluctuations of biogeochemicals in stream water. This article is protected by copyright. All rights reserved.