Impact of family history for endometriosis, migraine, depression and early menopause on endometriosis symptoms, localization and stage: A case control study

Introduction Endometriosis is a common disabling pain condition in women of childbearing age, frequently showing familial clustering. Nevertheless, little is known about whether familial predispositions influence its severity or presentation. In this study, we investigate disease characteristics in endometriosis patients with a family history (FH) for endometriosis or the comorbidities migraine, depression and early menopause (EMP). Materials and methods We performed an observational case-control study enrolling women with histologically confirmed endometriosis in a tertiary center. Based on surgical findings, patient records and phone interviews, we examined the relations between a FH for endometriosis, migraine, depression or EMP and endometriotic signs and symptoms, such as response to combined hormonal contraceptives (CHC) and analgesics, disease localization, infiltration depth, Enzian- and rASRM-scores. Results A positive FH for endometriosis, migraine, depression or EMP was reported by 10.2 %, 33.4 %, 32.6 % and 9.9 % of the 344 patients. A positive FH of endometriosis was associated with an increased risk for high rASRM-scores (rASRM 3 + 4: OR 2.74 (95 % CI 1.16–6.49), p = 0.017) and the presence of endometriomas (OR 2.70 (1.22–5.95), p = 0.011). A positive FH for migraine was associated with less response of endometriosis symptoms to CHC (OR 0.469 (0.27–0.82) p = 0.025). Depression in the family was linked to less severe rASRM-scores (rASRM 3 + 4: OR 0.63 (0.39–0.99), p = 0.046) and less endometriomas (OR 0.58 (0.67–0.92), p = 0.02), but increased the risk of both migraine (OR 1.66 (1.01–2.73), p = 0.043) and depression (OR 3.04 (1.89–4.89), p 5 days of non-cyclic pain (OR 3.58 (1.72–7.44), p < 0.001). Conclusions Around 30% reported a positive FH for migraine or depression. Patients with a positive FH for endometriosis, migraine, depression or EMP differ in symptoms and surgical findings when compared to controls. While a FH for endometriosis is associated with higher rASRM scores and more endometriomas, women with a FH for depression had lower rASRM scores and less endometriomas while responding better to CHC. In contrast, women with a FH for migraine showed less response to CHC

Endometriosis features and dienogest tolerability in women with depression: a case-control study

Objective Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. Methods This observational case-control study included endometriosis data from patients visiting our clinic from 2015–2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. Results 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). Conclusion EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood. SHORT CONDENSATION Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients

The portal of Neviaser: a valid option for antegrade nailing of humerus fractures

Introduction: The objective of this retrospective non-randomized study was to evaluate the portal of Neviaser (PN) as an alternative approach in antegrade humeral nailing. Methods: The surgical approach for the straight antegrade intramedullary nail (SAIN) was either the anterolateral delta-split (group 2, n = 79) or the portal of Neviaser (group 3, n = 27). Length of surgery and time of radiation were extracted from charts. Patients stabilized using the PN were followed for a clinical and radiological exam. At follow-up we evaluated the DASH (Disability of the Arm, Shoulder and Hand) and CMS (Constant-Murley Score). Results: Between 10.2015 and 12.2018 191 proximal and diaphyseal humeral fractures were operated using either an angular stable extramedullary device (group 1, PHILOS®, n = 85) or a straight humeral nail (MultiLoc®, n = 106). Time of radiation and intervention followed a normal distribution. The mean length of surgery was 172.9 min (SD 91.5) in group 1, 121.5 min (SD 54.1) in group 2 and 96.4 min (SD 33.7) in group 3 (p < 0.01). Time of radiation was significantly different with 1.1 min (SD 0.6: group 1), 3.1 min (SD 1.6: group 2) and 2.9 min (SD 1.7: group 3) (p < 0.01). After a mean interval of 21.5 months (range 6–43 months) 14 / 27 patients of group 3 were available for a clinical and radiological follow-up. The mean DASH in group 3 was 25, the CMS reached 70. The age and sex weighted CMS mean value was 96%. Forward flexion was 131°, abduction 125°. The ratio of strength affected versus non-affected side was 4.4: 6.2 kg. Conclusions: The portal of Neviaser is a feasible and safe approach and is an alternative to the anterolateral delta-split. Length of surgery and time of radiation were significantly shorter. Level of evidence: IV

Multicenter Standardization of Phase-Resolved Functional Lung MRI in Patients With Suspected Chronic Thromboembolic Pulmonary Hypertension

BACKGROUND Detection of pulmonary perfusion defects is the recommended approach for diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). This is currently achieved in a clinical setting using scintigraphy. Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is an alternative technique for evaluating regional ventilation and perfusion without the use of ionizing radiation or contrast media. PURPOSE To assess the feasibility and image quality of PREFUL-MRI in a multicenter setting in suspected CTEPH. STUDY TYPE This is a prospective cohort sub-study. POPULATION Forty-five patients (64 ± 16 years old) with suspected CTEPH from nine study centers. FIELD STRENGTH/SEQUENCE 1.5 T and 3 T/2D spoiled gradient echo/bSSFP/T2 HASTE/3D MR angiography (TWIST). ASSESSMENT Lung signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between study centers with different MRI machines. The contrast between normally and poorly perfused lung areas was examined on PREFUL images. The perfusion defect percentage calculated using PREFUL-MRI (QDP$_{PREFUL}$ ) was compared to QDP from the established dynamic contrast-enhanced MRI technique (QDP$_{DCE}$ ). Furthermore, QDP$_{PREFUL}$ was compared between a patient subgroup with confirmed CTEPH or chronic thromboembolic disease (CTED) to other clinical subgroups. STATISTICAL TESTS t-Test, one-way analysis of variance (ANOVA), Pearson's correlation. Significance level was 5%. RESULTS Significant differences in lung SNR and CNR were present between study centers. However, PREFUL perfusion images showed a significant contrast between normally and poorly perfused lung areas (mean delta of normalized perfusion -4.2% SD 3.3) with no differences between study sites (ANOVA: P = 0.065). QDP$_{PREFUL}$ was significantly correlated with QDP$_{DCE}$ (r = 0.66), and was significantly higher in 18 patients with confirmed CTEPH or CTED (57.9 ± 12.2%) compared to subgroups with other causes of PH or with excluded PH (in total 27 patients with mean ± SD QDP$_{PREFUL}$  = 33.9 ± 17.2%). DATA CONCLUSION PREFUL-MRI could be considered as a non-invasive method for imaging regional lung perfusion in multicenter studies. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 1

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results

Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes. The soluble bioactive form of the transmembrane protein fibronectin type III domain containing 4 (sFNDC4) has anti-inflammatory effects and improves insulin sensitivity. Here the authors show that liver derived sFNDC4 signals through adipose tissue GPCR GPR116 to promote insulin-mediated glucose uptake.Peer reviewe

Precision Newborn Screening for Lysosomal Disorders

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues. Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition software (Collaborative Laboratory Integrated Reports), which is freely available to newborn screening programs for selection of cases for which a biochemical second-tier test is needed. Results: Of five presumptive positive cases, one was affected with infantile Krabbe disease, two with Pompe disease, and one with MPS I. The remaining case was a heterozygote for the latter condition. The false-positive rate was 0.0018% and the positive predictive value was 80%. Conclusion: Postanalytical interpretive tools can drastically reduce false-positive outcomes, with preliminary evidence of no greater risk of false-negative events, still to be verified by long-term surveillance

Influence of lithology on hillslope morphology and response to tectonic forcing in the northern Sierra Nevada of California

Many geomorphic studies assume that bedrock geology is not a first-order control on landscape form in order to isolate drivers of geomorphic change (e.g., climate or tectonics). Yet underlying geology may influence the efficacy of soil production and sediment transport on hillslopes. We performed quantitative analysis of LiDAR digital terrain models to examine the topographic form of hillslopes in two distinct lithologies in the Feather River catchment in northern California, a granodiorite pluton and metamorphosed volcanics. The two sites, separated by <2 km and spanning similar elevations, were assumed to have similar climatic histories and are experiencing a transience in landscape evolution characterized by a propagating incision wave in response to accelerated surface uplift c. 5 Ma. Responding to increased incision rates, hillslopes in granodiorite tend to have morphology similar to model predictions for steady state hillslopes, suggesting that they adjust rapidly to keep pace with the incision wave. By contrast, hillslopes in metavolcanics exhibit high gradients but lower hilltop curvature indicative of ongoing transient adjustment to incision. We used existing erosion rate data and the curvature of hilltops proximal to the main channels (where hillslopes have most likely adjusted to accelerated erosion rates) to demonstrate that the sediment transport coefficient is higher in granodiorite (8.8 m2 ka-1) than in metavolcanics (4.8 m2 ka-1). Hillslopes in both lithologies get shorter (i.e., drainage density increases) with increasing erosion rates

Branched-chain and aromatic amino acid catabolism into aroma volatiles in Cucumis melo L. fruit

The unique aroma of melons (Cucumis melo L., Cucurbitaceae) is composed of many volatile compounds biosynthetically derived from fatty acids, carotenoids, amino acids, and terpenes. Although amino acids are known precursors of aroma compounds in the plant kingdom, the initial steps in the catabolism of amino acids into aroma volatiles have received little attention. Incubation of melon fruit cubes with amino acids and α-keto acids led to the enhanced formation of aroma compounds bearing the side chain of the exogenous amino or keto acid supplied. Moreover, L-[13C6]phenylalanine was also incorporated into aromatic volatile compounds. Amino acid transaminase activities extracted from the flesh of mature melon fruits converted L-isoleucine, L-leucine, L-valine, L-methionine, or L-phenylalanine into their respective α-keto acids, utilizing α-ketoglutarate as the amine acceptor. Two novel genes were isolated and characterized (CmArAT1 and CmBCAT1) encoding 45.6 kDa and 42.7 kDa proteins, respectively, that displayed aromatic and branched-chain amino acid transaminase activities, respectively, when expressed in Escherichia coli. The expression of CmBCAT1 and CmArAT1 was low in vegetative tissues, but increased in flesh and rind tissues during fruit ripening. In addition, ripe fruits of climacteric aromatic cultivars generally showed high expression of CmBCAT1 and CmArAT1 in contrast to non-climacteric non-aromatic fruits. The results presented here indicate that in melon fruit tissues, the catabolism of amino acids into aroma volatiles can initiate through a transamination mechanism, rather than decarboxylation or direct aldehyde synthesis, as has been demonstrated in other plants

Synaptic processes and immune-related pathways implicated in Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS