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This study aimed to compare and evaluate the prediction accuracy and risk of bias (ROB) of post-traumatic stress disorder (PTSD) predictive models. We conducted a systematic review and random-effect meta-analysis summarizing predictive model development and validation studies using machine learning in diverse samples to predict PTSD. Model performances were pooled using the area under the curve (AUC) with a 95% confidence interval (CI). Heterogeneity in each meta-analysis was measured using I 2 . The risk of bias in each study was appraised using the PROBAST tool. 48% of the 23 included studies had a high ROB, and the remaining had unclear. Tree-based models were the primarily used algorithms and showed promising results in predicting PTSD outcomes for various groups, as indicated by their pooled AUCs: military incidents (0.745), sexual or physical trauma (0.861), natural disasters (0.771), medical trauma (0.808), firefighters (0.96), and alcohol-related stress (0.935). However, the applicability of these findings is limited due to several factors, such as significant variability among the studies, high and unclear risks of bias, and a shortage of models that maintain accuracy when tested in new settings. Researchers should follow the reporting standards for AI/ML and adhere to the PROBAST guidelines. It is also essential to conduct external validations of these models to ensure they are practical and relevant in real-world settings., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. This systematic review did not involve direct data collection from humans or animals, and, therefore, did not require ethics approval. Consent for publication: Not applicable. This manuscript does not contain any personal data from individuals. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The authors' previous research suggested the hypothesis that aesthetic surgery in general has a positive impact on quality of life (QoL). This prospective study aimed to investigate the indication-specific effect on QoL in patients undergoing transaxillary endoscopic breast augmentation., Methods: Seventy-seven patients underwent aesthetic breast augmentation. Fifty patients met the inclusion criteria. All of them answered one set of the questionnaires preoperatively, and the follow-up set at 6 months postoperatively. The testing instruments included a self-developed indication-specific questionnaire and five standardised and validated questionnaires with German norm data available: Questions on Life Satisfaction, Modules (FLZ M , German version), the Freiburg Personality Inventory-Revised (FPI-R), the Rosenberg Self-Esteem Scale (SRES), the Patient Health Questionnaire (PHQ-4) and the Breast-Q | Augmentation., Results: Our self-developed indication-specific questionnaire shows high satisfaction with the postoperative results. The FLZ M demonstrated significant improvements in the module life in general (p < 0.001), 'hobbies' (p < 0.001), 'health' (p = 0.04), 'family life' (p = 0.03) and 'partner relationship/sexuality' (p < 0.001). Moreover, the FPI-R revealed a significant improvement in emotional stability (p < 0.001). Moreover, the PHQ-4 showed a significant reduction in overall psychological distress (p < 0.001). Further, Breast-Q indicated a significant increase in psychological (p < 0.001) and sexual well-being (p < 0.001)., Conclusion: Transaxillary endoscopic breast augmentation has a significant impact on QoL and sexuality. The surgery leads to a higher satisfaction not only with the result of intervention and the outer appearance specifically, but also with life and the state of health generally. It improves emotional stability. Therefore, the authors' hypothesis in a previous research was confirmed for this specific indication prospectively., (Copyright © 2024. Published by Elsevier Ltd.)

The conserved process of centriole duplication requires establishment of a Sas6-centred cartwheel initiated by Plk4's phosphorylation of Ana1/STIL. Subsequently the centriole undergoes conversion to a centrosome requiring its radial expansion and elongation, mediated by a network requiring interactions between Cep135, Ana1/Cep295, and Asterless/Cep152. Here we show that mutant alleles encoding overlapping N- and C-terminal parts of Ana1 are capable of intragenic complementation to rescue radial expansion. This permits recruitment of Asl and thereby centriole duplication and mechanosensory cilia formation to restore the coordination defects of these mutants. This genetic combination also rescues centriole duplication in the male germ line but does not rescue the elongation of the triplet microtubule-containing centrioles of primary spermatocytes and consequently these males are coordinated but sterile. Such centriole elongation is rescued by the continuous, full-length Ana1 sequence. We define a region that when deleted within otherwise intact Ana1 does not permit primary spermatocyte centrioles to elongate but still allows recruitment of Asl. Our findings point to differing demands upon the physical organization of Ana1 for the distinct processes of radial expansion and elongation of centrioles.

Silver nanoparticles (AgNPs) are known to affect the physiology and morphology of plants in various ways, but the exact mechanism by which they interact with plant cells remains to be elucidated. An unresolved question of silver nanotoxicology is whether the interaction is triggered by the physical features of the particles, or by silver ions leached from their surface. In this study, we germinated and grew Arabidopsis thaliana seedlings in synthetic medium supplemented with sub-morbid concentrations (4 μg/mL) of AgNPs and silver nitrate (AgNO 3 ). This treatment led to in planta accumulation of 106 μg/g and 97 μg/g of silver in the AgNO 3 - and AgNP-exposed seedlings, respectively. Despite the statistically indistinguishable silver accumulation, RNA sequencing data demonstrated distinct changes in the transcriptome of the AgNP-exposed, but not in the AgNO 3 -exposed plants. AgNP exposure induced changes in the expression of genes involved in immune response, cell wall organization, photosynthesis and cellular defense against reactive oxygen species. AgNO 3 exposure, on the other hand, caused the differential expression of only two genes, neither of which belonged to any AgNP-enriched gene ontology categories. Moreover, AgNP exposure led to a 39% reduction (p < 0.001) in total chlorophyll concentration relative to untreated plants which was associated with a 56.9% and 56.2% drop (p < 0.05) in carbon assimilation rate at ambient and saturating light, respectively. Stomatal conductance was not significantly affected by AgNP exposure, and limitations to carbon assimilation, as determined through analysis of light and carbon dioxide (A/Ci) curves, were attributed to rates of electron transport, maximum carboxylation rates and triose phosphate use. AgNO 3 -exposure, on the other hand, did not lead to significant reduction either in chlorophyll concentration or in carbon assimilation rate. Given these data, we propose that the impact of AgNPs cannot be simply attributed to the presence of the metal in plants, but is innate to the particulate nature of nanosilver., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn 2+ . Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.

Acute lung injury (ALI) is characterized by lung vascular endothelial cell (EC) barrier compromise resulting in increased endothelial permeability and pulmonary edema. The infection of gram-negative bacteria that produce toxins like LPS is one of the major causes of ALI. LPS activates Toll-like receptor 4, leading to cytoskeleton reorganization, resulting in lung endothelial barrier disruption and pulmonary edema in ALI. However, the signaling pathways that lead to the cytoskeleton reorganization and lung microvascular EC barrier disruption remain largely unexplored. Here we show that LPS induces calpain activation and talin cleavage into head and rod domains and that inhibition of calpain attenuates talin cleavage, RhoA activation, and pulmonary EC barrier disruption in LPS-treated human lung microvascular ECs in vitro and lung EC barrier disruption and pulmonary edema induced by LPS in ALI in vivo . Moreover, overexpression of calpain causes talin cleavage and RhoA activation, myosin light chain (MLC) phosphorylation, and increases in actin stress fiber formation. Furthermore, knockdown of talin attenuates LPS-induced RhoA activation and MLC phosphorylation and increased stress fiber formation and mitigates LPS-induced lung microvascular endothelial barrier disruption. Additionally, overexpression of talin head and rod domains increases RhoA activation, MLC phosphorylation, and stress fiber formation and enhances lung endothelial barrier disruption. Finally, overexpression of cleavage-resistant talin mutant reduces LPS-induced increases in MLC phosphorylation in human lung microvascular ECs and attenuates LPS-induced lung microvascular endothelial barrier disruption. These results provide the first evidence that calpain mediates LPS-induced lung microvascular endothelial barrier disruption in ALI via cleavage of talin.

Pretargeted concept in positron emission tomography (PET) together with bioorthogonal chemistry is an elegant solution to study processes with slow pharmacokinetics by utilizing radiotracers labeled with short-lived radionuclides. Namely, radiotracers based on tetrazine ligation with trans -cyclooctene (TCO) via the inverse electron demand Diels-Alder (IEDDA) reaction have become a state-of-the-art for the pretargeted PET imaging. For radiolabeling of tetrazine scaffolds, indirect radiofluorination methods are often preferred, as tetrazines are vulnerable to harsh conditions typically necessary for the direct radiofluorination. 18 F-Fluoroglycosylation is an indirect radiofluorination method, which allows the introduction of a widely accessible glucose analog 2-[ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]FDG) to aminooxy-functionalized precursors via oxime formation. Here, we report the biological evaluation of [ 18 F]FDG-Tz as a tracer for pretargeted PET imaging of TCO-functionalized molecular spherical nucleic acids (MSNA) against human epidermal growth factor receptor 2 (HER2) mRNA. The oxime ether formation between [ 18 F]FDG and tetrazine oxyamine resulted in [ 18 F]FDG-Tz with high radiochemical purity (>99%) and moderate yields (6.5 ± 3.6%, n = 5). Biological evaluation of [ 18 F]FDG-Tz in healthy mice indicated favorable pharmacokinetics with quick blood clearance, urinary excretion as the main elimination route, and the absence of GLUT1 transportation. The successful pretargeted experiments with TCO-functionalized MSNA revealed higher tumor uptake compared to preclicked MSNA in HER2-expressing human breast cancer xenograft-bearing mice., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: To describe the thresholds of instability used by clinicians at reintubation and evaluate the accuracy of different combinations of criteria in predicting reintubation decisions., Design: Secondary analysis using data obtained from the prospective observational Automated Prediction of Extubation Readiness study (NCT01909947) between 2013 and 2018., Setting: Multicentre (three neonatal intensive care units)., Patients: Infants with birth weight ≤1250 g, mechanically ventilated and undergoing their first planned extubation were included., Interventions: After extubation, hourly O 2 requirements, blood gas values and occurrence of cardiorespiratory events requiring intervention were recorded for 14 days or until reintubation, whichever came first., Main Outcome Measures: Thresholds at reintubation were described and grouped into four categories: increased O 2 , respiratory acidosis, frequent cardiorespiratory events and severe cardiorespiratory events (requiring positive pressure ventilation). An automated algorithm was used to generate multiple combinations of criteria from the four categories and compute their accuracies in capturing reintubated infants (sensitivity) without including non-reintubated infants (specificity)., Results: 55 infants were reintubated (median gestational age 25.2 weeks (IQR 24.5-26.1 weeks), birth weight 750 g (IQR 640-880 g)), with highly variable thresholds at reintubation. After extubation, reintubated infants had significantly greater O 2 needs, lower pH, higher pCO 2 and more frequent and severe cardiorespiratory events compared with non-reintubated infants. After evaluating 123 374 combinations of reintubation criteria, Youden indices ranged from 0 to 0.46, suggesting low accuracy. This was primarily attributable to the poor agreement between clinicians on the number of cardiorespiratory events at which to reintubate., Conclusions: Criteria used for reintubation in clinical practice are highly variable, with no combination accurately predicting the decision to reintubate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Many anticancer drugs exhibit high systemic off-target toxicities causing severe side effects. Peptide-drug conjugates (PDCs) that target tumor-specific receptors such as integrin α v β 6 are emerging as powerful tools to overcome these challenges. The development of an integrin α v β 6 -selective PDC was achieved by combining the therapeutic efficacy of the cytotoxic drug monomethyl auristatin E with the selectivity of the α v β 6 -binding peptide (α v β 6 -BP) and with the ability of positron emission tomography (PET) imaging by copper-64. The [ 64 Cu]PDC- 1 was produced efficiently and in high purity. The PDC exhibited high human serum stability, integrin α v β 6 -selective internalization, cell binding, and cytotoxicity. Integrin α v β 6 -selective tumor accumulation of the [ 64 Cu]PDC- 1 was visualized with PET-imaging and corroborated by biodistribution, and [ 64 Cu]PDC- 1 showed promising in vivo pharmacokinetics. The [ nat Cu]PDC- 1 treatment resulted in prolonged survival of mice bearing α v β 6 (+) tumors (median survival: 77 days, vs α v β 6 (-) tumor group 49 days, and all other control groups 37 days).

We present measurements of the cross section and double-helicity asymmetry A&#95;{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510  GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510  GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

Even though, nowadays, cancer is one of the leading causes of death, too little is known about the behavior of this disease due to its unpredictability from one patient to another. Classical mathematical models of tumor growth have shaped our understanding of cancer and have broad practical implications for treatment scheduling and dosage. However, improvements are still necessary on these models. The primary objective of the present research is to prove the efficiency of fractional order calculus in mathematical oncology, more specifically in tumor growth modeling. For this, a generalization of the four most used differential equation models in tumor volume measurements fitting is realized, using the corresponding fractional order equivalent. Are established the fractional order Exponential, Logistic, Gompertz, General Bertalanffy-Pütter and Classical Bertalanffy-Pütter models for a treated and untreated dataset. The obtained results are compared by Mean Squared Error (MSE) with the integer order correspondent of each model. The results prove the superiority of the fractional order models. The MSE of fractional order models are reduced at least at half in comparison with the MSE of the integer order equivalent. It is demonstrated in this way that fractional order deterministic models can offer a good starting point in finding a proper mathematical model for tumor evolution prediction. Fractional calculus is a suitable method in this case due to its memory property, aspect that particularly characterizes biological processes., (© 2023. The Author(s).)

Background: Our previous retrospective study indicates that esthetic surgery in general results in a significant improvement in Quality of life (QoL). This is the first indication-specific prospective evaluation of QoL after blepharoplasty using standardized and validated questionnaires., Objectives: To report changes in QoL after blepharoplasty prospectively with a 6-month follow-up., Methods: The same surgical team performed an esthetic blepharoplasty on 50 patients. Participants answered 1 set of questionnaires preoperatively and 6 months postoperatively. The instrument consisted of a self-developed indication-specific part specially designed for blepharoplasty and 4 validated and standardized testing instruments (FLZ, FPI-R, RSES, and PHQ-4) with norm data for German-speaking countries available., Results: This study reveals a high rate of satisfaction after blepharoplasty. 96% felt better about themselves and 94% would undergo the procedure again. Statistically significant increased values were found postoperatively in the items "income" ( P =0.016), "family life" ( P =0.028), "partner relationship" ( P =0.039), "ability to relax" ( P <0.001), "energy" ( P <0.001), "hobbies" ( P <0.001), and with their outer appearance in general ( P =0.018). Blepharoplasty showed a statistically significant improvement in emotional stability ( P =0.017) and a reduction in depressive symptoms ( P <0.001). Our patients had statistically significantly higher self-esteem before ( P <0.001) and after ( P <0.001) the intervention., Conclusion: Our prospective study shows that blepharoplasty increases most aspects of QoL significantly, has a positive effect on emotional and physical well-being, and reduces the incidence of depressive symptoms and anxiety., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Extremely preterm infants are frequently subjected to mechanical ventilation. Current prediction tools of extubation success lacks accuracy., Methods: Multicenter study including infants with birth weight ≤1250 g undergoing their first extubation attempt. Clinical data and cardiorespiratory signals were acquired before extubation. Primary outcome was prediction of extubation success. Automated analysis of cardiorespiratory signals, development of clinical and cardiorespiratory features, and a 2-stage Clinical Decision-Balanced Random Forest classifier were used. A leave-one-out cross-validation was done. Performance was analyzed by ROC curves and determined by balanced accuracy. An exploratory analysis was performed for extubations before 7 days of age., Results: A total of 241 infants were included and 44 failed (18%) extubation. The classifier had a balanced accuracy of 73% (sensitivity 70% [95% CI: 63%, 76%], specificity 75% [95% CI: 62%, 88%]). As an additional clinical-decision tool, the classifier would have led to an increase in extubation success from 82% to 93% but misclassified 60 infants who would have been successfully extubated. In infants extubated before 7 days of age, the classifier identified 16/18 failures (specificity 89%) and 73/105 infants with success (sensitivity 70%)., Conclusions: Machine learning algorithms may improve a balanced prediction of extubation outcomes, but further refinement and validation is required., Impact: A machine learning-derived predictive model combining clinical data with automated analyses of individual cardiorespiratory signals may improve the prediction of successful extubation and identify infants at higher risk of failure with a good balanced accuracy. Such multidisciplinary approach including medicine, biomedical engineering and computer science is a step forward as current tools investigated to predict extubation outcomes lack sufficient balanced accuracy to justify their use in future trials or clinical practice. Thus, this individualized assessment can optimize patient selection for future trials of extubation readiness by decreasing exposure of low-risk infants to interventions and maximize the benefits of those at high risk., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To describe the timing of first extubation in extremely preterm infants and explore the relationship between age at first extubation, extubation outcome, and death or respiratory morbidities., Study Design: In this subanalysis of a multicenter observational study, infants with birth weights of 1250 g or less and intubated within 24 hours of birth were included. After describing the timing of first extubation, age at extubation was divided into early (within 7 days from birth) vs late (days of life 8-35), and extubation outcome was divided into success vs failure (reintubation within 7 days after extubation), to create 4 extubation groups: early success, early failure, late success, and late failure. Logistic regression analyses were performed to evaluate associations between the 4 groups and death or bronchopulmonary dysplasia, bronchopulmonary dysplasia among survivors, and durations of respiratory support and oxygen therapy., Results: Of the 250 infants included, 129 (52%) were extubated within 7 days, 93 (37%) between 8 and 35 days, and 28 (11%) beyond 35 days of life. There were 93, 36, 59, and 34 infants with early success, early failure, late success, and late failure, respectively. Although early success was associated with the lowest rates of respiratory morbidities, early failure was not associated with significantly different respiratory outcomes compared with late success or late failure in unadjusted and adjusted analyses., Conclusions: In a contemporary cohort of extremely preterm infants, early extubation occurred in 52% of infants, and only early and successful extubation was associated with decreased respiratory morbidities. Predictors capable of promptly identifying infants with a high likelihood of early extubation success or failure are needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/aim: Despite remission or low disease activity non-inflammatory complaints like exhaustion, fatigue, and pain persist in a significant proportion of patients with systemic lupus erythematosus (SLE) and have a considerable impact on health-related quality of life. This study evaluated the effects of balneotherapy on non-inflammatory complaints, quality of life, and work productivity of patients with SLE., Patients and Methods: SLE patients in remission/low disease activity in three rheumatology centers were included in this randomized, controlled, follow-up study. In addition to the standard of care (SOC), sixteen out of the thirty patients with SLE received balneotherapy (3-week period, 15 times, for 30 min) and fourteen patients received the SOC only. Pre-validated survey instruments including Lupus Quality of Life (LupusQoL), Short-Form Health Survey (SF-36), Work Productivity, and Activity Impairment-Lupus (WPAI-Lupus) questionnaires were used., Results: Based on the SF-36 questionnaires, several subdomains of physical condition improved significantly after the course; the improvement remained durable (p=0.019). General health improved significantly by the end of the course (p=0.001). According to the LupusQoL questionnaire, physical health and pain showed a tendency of improvement shortly after the spa treatment. Changes in the WPAI-lupus questionnaire indicated a short-term improvement of the daily activity by the end of the observation period. No adverse reactions were observed., Conclusion: Thermal water therapy may be an effective, well-tolerated, complementary non-pharmacological approach for non-inflammatory complaints of patients with SLE. Physical condition improved in the short-term, whereas fatigue worsened despite treatment., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The ability to relocalize proteins to defined subcellular locations presents a powerful tool to examine protein-protein interactions that can overcome a tendency of non-targeted exogenous proteins to form inaccessible aggregates. Here, we show that a 24-amino-acid sequence from the Drosophila proapoptotic protein Hid's tail anchor (HTA) domain can target exogenous proteins to the mitochondria in Drosophila cells. We use this HTA tag to target the Drosophila centriole cartwheel protein Sas6 to the mitochondria, and show that both exogenous and endogenous Gorab can be co-recruited from the Golgi to the new mitochondrial site. This accords with our previous observation that monomeric Drosophila Gorab binds Sas6 to become centriole associated with a 50-fold greater affinity than dimeric Gorab binds Rab6 to become localized at the Golgi. Strikingly, Drosophila Sas6 can bind both Drosophila Gorab and its human GORAB ortholog, whereas human SAS6 is unable to bind either GORAB or Gorab. We discuss these findings in relation to the evolutionary conservation of Gorab and the divergence of Sas6, possibly reflecting known differences in persistence of the cartwheel in the centriole duplication cycle of fly and human cells., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Background: Prognostic value of proton MR spectroscopy (H-MRS) in hypoxic-ischemic encephalopathy (HIE) is acknowledged; however, effects of gestational age (GA) and postnatal age (PA) on prediction and metabolite levels are unknown., Methods: One hundred and sixty-nine newborns with moderate-to-severe HIE were studied, having ≥1 H-MRS scan during postnatal days 0-14 and known neurodevelopmental outcome (Bayley-II score/cerebral palsy/death). Initial scans were categorized by PA (day 1-3/4-6/≥7), and metabolite ratios were compared by predictive value. Metabolite dynamics were assessed in a total of 214 scans performed in the study population, using regression modeling, with predictors GA, PA, and outcome., Results: N-acetyl-aspartate (NAA)/creatine (Cr) and myo-inositol (mI)/NAA height ratios were consistently associated with outcome throughout the first 14 days, with the highest predictive value in the late (≥7 days) period (AUC = 0.963 and 0.816, respectively). Neither GA nor PA had an overall effect on these metabolite ratios, which showed strongest association with outcome (p < 0.001). Assessed separately in patients with good outcome, GA became a significant covariate for metabolite ratios (p = 0.0058 and 0.0002, respectively). However, this association disappeared in the poor outcome group., Conclusions: In HIE, NAA/Cr and mI/NAA give most accurate outcome prediction throughout postnatal days 0-14. GA only affected metabolite levels in the good outcome group., Impact: Proton MR spectroscopy metabolite ratios N-acetyl-aspartate/creatine and myo-inositol/N-acetyl-aspartate have persistently high predictive value throughout postnatal days 0-14 in newborns with hypoxic-ischemic encephalopathy, with the highest predictive power between postnatal days 7 and 14. Overall, neither metabolite ratio was affected by gestational age nor by postnatal age, while they showed the strongest association with neurological outcome. However, in newborns facing good outcome, metabolite ratios were associated with gestational age, whereas in cases facing poor outcome, this association disappeared. Proton MR spectroscopy provides valuable prognostic information in neonatal hypoxic-ischemic encephalopathy throughout the first 2 weeks of life, irrespective of the timing of MR scan., (© 2021. The Author(s).)

Background: There is a lack of data concerning the prevalence of eating disorders in patients requesting aesthetic surgery in spite of a large body of literature on the psychopathology of these patients. This may mostly be due to insufficient diagnostic assessment instruments. Therefore, the aim of this study was to determine the prevalence of eating disorders and their comorbidities in patients undergoing aesthetic surgery., Methods: The assessment of prevalence of the eating disorders as anorexia nervosa, bulimia nervosa and binge eating disorder as well as other mental disorders was performed with the Structured Clinical Interview for DSM-IV mental disorders (SCID), axis 1., Results: 212 patients (198 females, 14 males), requesting different types of aesthetic surgery, were included in this study. Eating disorders had a current prevalence of 8.0% (17/212) and a lifetime prevalence of 11.3% (24/212). Anorexia nervosa was predominantly found in patients with breast augmentation [current: 7.4% (2/27); lifetime: 11.1% (3/27)] and rhinoplasty [6.3 (1/16); 12.6% (2/16)]. Bulimia nervosa dominated in patients with liposuction [10% (3/30); 13.3% (4/30)] and binge eating disorder in patients with abdominoplasty [current/lifetime: 10.8% (4/37)]. Levels of significance (p ≤ 0.002) were reached for prevalence of the eating disorders in above mentioned types of surgery, when compared to prevalence data of the general population (two proportion Z test for SPSS)., Conclusion: Eating disorders are distributed according to a certain pattern in the different types of aesthetic surgery. Interestingly, the current prevalence of eating disorders (17/212) was comparable to that of body dysmorphic disorder (26/212)., (Copyright © 2021. Published by Elsevier Ltd.)

Thanks to the advent of combination antiretroviral therapy (cART), people living with human immunodeficiency virus (HIV) (PLWH) experienced a marked increase in life expectancy but are now at higher risk for cardiovascular disease (CVD), the current leading cause of death in PLWH on cART. Although HIV preponderantly affects men over women, manifestations of HIV-related CVD differ by sex with women experiencing greater risks than men. Despite extensive investigation, the etiopathology of CVD, notably the respective contribution of viral infection and cART, remain ill-defined. However, both viral infection and cART have been reported to contribute to endothelial dysfunction, the precursor and major cause of atherosclerosis-associated CVD, through mechanisms involving endothelial cell activation, inflammation, and oxidative stress, all leading to reduced nitric oxide bioavailability. Therefore, preserving endothelial function in PLWH on cART should be a main target to reduce CVD morbidity and mortality, notably in females., Competing Interests: Support for this work was provided by NIH 1R01HL147639-01A1, and AHA 19EIA34760167 to Dr Belin de Chantemèle and AHA 21PRE830396 to Mr Kress. Dr Kovacs has reported that he has no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Cancer and atherosclerosis are chronic diseases that share common characteristics at both early and advanced stages and can arise from multiple factors. Both diseases are characterized by uncontrolled cell proliferation, inflammation, angiogenesis and apoptosis. Herein we investigated the ability of a peptide (CTHRSSVVC), that was previously reported to bind atherosclerotic lesions to home in the tumor microenvironment. The CTHRSSVVC peptide was synthesized on solid phase and N-terminally labeled with a sulfo-Cy5 dye. The specific binding to macrophage was evaluated in vitro with flow cytometry and immunofluorescence and in vivo for tumor targeting in BALB/c mice bearing a 4T1 tumor using optical imaging. The sulfo-Cy5-CTHRSSVVC peptide was synthesized in greater than 99% purity. No selective binding of the sulfo-Cy5-CTHRSSVVC peptide to macrophages in vitro was observed, however in vivo the sulfo-Cy5-CTHRSSVVC peptide accumulated in the 4T1 tumor, with a tumor-to-normal tissue ratio of 7.21 ± 1.44 at 2 h post injection. Ex vivo analysis of tumor tissue by confocal microscopy suggested that the sulfo-Cy5-CTHRSSVVC peptide had accumulated in the stroma of the tumor specifically, in regions of spindle shaped cells. In conclusion, although the target for the sulfo-Cy5-CTHRSSVVC peptide remains to be identified, the Cy5-CTHRSSVVC peptide warrants further investigation as a tumor imaging agent., (Copyright © 2021. Published by Elsevier Masson SAS.)

Chronic obstructive pulmonary disease (COPD) is a multisystemic respiratory disease that is associated with progressive airway and pulmonary vascular remodeling due to the increased proliferation of bronchial smooth muscles cells (BSMCs) and pulmonary arterial smooth muscle cells (PASMCs) and the overproduction of extracellular matrix (e.g., collagen). Cigarette smoke (CS) and several mediators, such as PDGF (platelet-derived growth factor) and IL-6, play critical roles in COPD pathogenesis. HDAC6 has been shown to be implicated in vascular remodeling. However, the role of airway HDAC6 signaling in pulmonary vascular remodeling in COPD and the underlying mechanisms remain undetermined. Here, we show that HDAC6 expression is upregulated in the lungs of patients with COPD and a COPD animal model. We also found that CS extract (CSE), PDGF, and IL-6 increase the protein levels and activation of HDAC6 in BSMCs and PASMCs. Furthermore, CSE and these stimulants induced deacetylation and phosphorylation of ERK1/2 and increased collagen synthesis and BSMC and PASMC proliferation, which were outcomes that were prevented by HDAC6 inhibition. Inhibition of ERK1/2 also diminished the CSE-, PDGF-, and IL-6-caused elevation in collagen levels and cell proliferation. Pharmacologic HDAC6 inhibition with tubastatin A prevented the CS-stimulated increases in the thickness of the bronchial and pulmonary arterial wall, airway resistance, emphysema, and right ventricular systolic pressure and right ventricular hypertrophy in a rat model of COPD. These data demonstrate that the upregulated HDAC6 governs the collagen synthesis and BSMC and PASMC proliferation that lead to airway and vascular remodeling in COPD.

People living with human immunodeficiency virus (HIV) (PLWH) have increased risk for atherosclerosis-related cardiovascular disease (CVD), the main cause of death in this population. Notwithstanding, the mechanisms of HIV-associated vascular pathogenesis are not fully elucidated. Therefore, we sought to determine whether HIV-regulatory protein Tat mediates HIV-induced endothelial dysfunction via NADPH oxidase 1 (Nox1)-dependent mechanisms. Body weight, fat mass, leptin levels, expression of reactive oxygen species (ROS)-producing enzymes and vascular function were assessed in C57BL/6 male mice treated with Tat for 3 days and 4 weeks. Aortic rings and human endothelial cells were also treated with Tat for 2-24 h in ex vivo and in vitro settings. Chronic (4 weeks) but not acute (3 days and 2-24 h) treatment with Tat decreased body weight, fat mass, and leptin levels and increased the expression of Nox1 and its coactivator NADPH oxidase Activator 1 (NoxA1) . This was associated with impaired endothelium-dependent vasorelaxation. Importantly, specific inhibition of Nox1 with GKT771 and chronic leptin infusion restored endothelial function in Tat-treated mice. These data rule out direct effects of HIV-Tat on endothelial function and imply the contribution of reductions in adipose mass and leptin production which likely explain upregulated expression of Nox1 and NoxA1. The Nox1 and leptin system may provide potential targets to improve vascular function in HIV infection-associated CVD.

Abstract: Dobrosielski, DA, Leppert, KM, Knuth, ND, Wilder, JN, Kovacs, L, and Lisman, PJ. Body composition values of NCAA Division 1 female athletes derived from dual-energy x-ray absorptiometry. J Strength Cond Res 35(10): 2886-2893, 2021-This study generated descriptive data for regional and total body composition and bone mineral density (BMD) measures using dual-energy x-ray absorptiometry (DXA) across 12 NCAA Division 1 female competitive sports. Two hundred seventy-eight female collegiate athletes underwent DXA: basketball (BB; n = 28), cross country (CC = 11), field hockey (FH; n = 35), gymnastics (GYM; n = 23), lacrosse (LAX; n = 48), soccer (SOC; CC = 27), softball (SB; n = 24), swimming and diving (SW; n = 35), tennis (TN; n = 11), track and field ([TR-throw; n = 10]; [TR-run; n = 10]), and volleyball (VB; n = 16). Descriptive statistics for all body composition and BMD measures were calculated. Group mean differences in all regional and total body composition (all, p < 0.001; η2 range = 0.177-0.365) and BMD (all, p < 0.001; η2 range = 0.317-0.383) measures were observed between teams. The total BF% for gymnasts (23.5%) was lower than TN, FH, LAX, SB, and TR-throw (mean difference range: -4.6 to -12.9%, all p < 0.01); TR-throw had the highest total BF% (36.4%). Cross country had lower total BMD (1.17 g·cm-2) than FH, TR-throw, LAX, GYM, SOC, SB, VB, and BB (mean difference range: -0.12 to -0.26 g·cm-2, all p < 0.01); BB and TR-throw had the highest total BMD (1.40 and 1.43 g·cm-2, respectively). Our data confirm that regional and total body composition and BMD measures varied across female collegiate sports. These findings may assist sports medicine and strength and conditioning practitioners with identifying sport-specific goal values for BF% and BMD to optimize program design., (Copyright © 2019 National Strength and Conditioning Association.)

During the past decades, the relationship between various psychological parameters had been studied in detail. However, the dependency structure of correlated parameters was rarely investigated. Knowing the dependence structure helps in finding the probability matrix of the interaction between the parameters. In this research, a novel approach was introduced in psychological analysis using copula functions. For this purpose, the self-esteem and anxiety of 141 university students in Iran were extracted using the Coopersmith Self-esteem Inventory and the Zang Anxiety Scale. Then the dependence structure of self-esteem and anxiety were established using copula functions. The Frank copula achieved the best fit for the joint variables of self-esteem and anxiety. Finally, the probability matrix of different classes of anxiety, taking into account self-esteem classes, was extracted. The results indicated that poor self-esteem leads to severe or very severe anxiety, with more than 98% probability, while strong self-esteem may lead to normal and mild anxiety, with about 80% probability. It can be concluded that the method was promising, and that copula functions can open a window to the dependence structure analysis of psychological parameters.

Background: Partly as a result of the increasing attention directed toward transgender individuals and despite much research work on the topic of quality of life (QOL) of transgender, there is still a lack of studies using standardized questionnaires in their evaluation., Aims: We designed a survey to evaluate the influence of surgery after phalloplasty (osteofasciocutaneous fibula free flap or osteofasciocutaneous radial free forearm flap) on QOL, emotional stability, self-esteem, and psyche of postoperated transgender men., Methods: The present study included 32 transgender men who had undergone gender-affirming surgery (GAS) exclusively in our department between 2000 and 2012. Apart from our self-developed, indication-specific questionnaire with questions on socioeconomic and demographic data as well as postoperative satisfaction, the testing instrument included 4 frequently used, standardized testing instruments, which we compared with normative data. These included (a) a self-assessment test Fragebogen zur Lebenszufriedenheit with questions on QOL consisting of 3 modules (general satisfaction, satisfaction with health, and satisfaction with body image/outer appearance), (b) the Freiburg Personality Inventory, (c) the Rosenberg Self-Esteem Questionnaire, and (d) the Patient Health Questionnaire 4., Findings: Our self-developed, indication-specific questionnaire showed that 88% of our patients were very satisfied with the aesthetic result, 75% have had sex after surgery, and 72% were very satisfied with sexual function after GAS. Eighty-one percent had a strong improvement of QOL, and 91% would undergo the same treatment again. Eighty-four percent would recommend GAS to others. All patients lived as men fulltime., Discussion: Our study reveals that GAS plays an important part in the interdisciplinary treatment of transgender individuals as it improves the QOL in transgender men in most aspects of everyday life and has a positive influence on the patients' psyche and self-esteem in a retrospective study., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Acute lung injury (ALI) is an acute inflammatory process arises from a wide range of lung insults. A major cause of ALI is dysfunction of the pulmonary vascular endothelial barrier but the mechanisms involved are incompletely understood. The therapeutic potential of histone deacetylase (HDAC) inhibitors for the treatment of cardiovascular and inflammatory diseases is increasingly apparent, but the mechanisms by which HDACs regulate pulmonary vascular barrier function remain to be resolved. We found that specific Class IIa HDACs inhibitor, TMP269, significantly attenuated the lipopolysaccharide (LPS)-induced human lung microvascular endothelial cells (HLMVEC) barrier compromise in vitro and improved vascular barrier integrity and lung function in murine model of ALI in vivo. TMP269 decreased LPS-induced myosin light chain phosphorylation suggesting the role for Class IIa HDACs in LPS-induced cytoskeleton reorganization. TMP269 did not affect microtubule structure and tubulin acetylation in contrast to the HDAC6-specific inhibitor, Tubastatin A suggesting that Class IIa HDACs and HDAC6 (Class IIb) regulate endothelial cytoskeleton and permeability via different mechanisms. Furthermore, LPS increased the expression of ArgBP2 which has recently been attributed to HDAC-mediated activation of Rho. Depletion of ArgBP2 abolished the ability of LPS to disrupt barrier function in HLMVEC and both TMP269 and Tubastatin A decreased the level of ArgBP2 expression after LPS stimulation suggesting that both Class IIa and IIb HDACs regulate endothelial permeability via ArgBP2-dependent mechanism. Collectively, our data strongly suggest that Class IIa HDACs are involved in LPS-induced ALI in vitro and in vivo via specific mechanism which involved contractile responses, but not microtubule reorganization., (© 2020 Wiley Periodicals LLC.)

The duplication and ninefold symmetry of the Drosophila centriole requires that the cartwheel molecule, Sas6, physically associates with Gorab, a trans-Golgi component. How Gorab achieves these disparate associations is unclear. Here, we use hydrogen-deuterium exchange mass spectrometry to define Gorab's interacting surfaces that mediate its subcellular localization. We identify a core stabilization sequence within Gorab's C-terminal coiled-coil domain that enables homodimerization, binding to Rab6, and thereby trans-Golgi localization. By contrast, part of the Gorab monomer's coiled-coil domain undergoes an antiparallel interaction with a segment of the parallel coiled-coil dimer of Sas6. This stable heterotrimeric complex can be visualized by electron microscopy. Mutation of a single leucine residue in Sas6's Gorab-binding domain generates a Sas6 variant with a sixteenfold reduced binding affinity for Gorab that cannot support centriole duplication. Thus, Gorab dimers at the Golgi exist in equilibrium with Sas6-associated monomers at the centriole to balance Gorab's dual role., Competing Interests: AF, ES, MR, LK, ZP, MP, GD, MD, DG No competing interests declared, (© 2021, Fatalska et al.)

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform., Aims: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD., Design: On-line survey in endocrine centres throughout Europe., Patients and Methods: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018., Results: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved., Conclusion: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

Introduction: Periprosthetic joint infection (PJI) is a severe complication after a total knee replacement that is primarily associated with soft tissue defects. Finding an appropriate therapy for PJI is a major challenge because of the lack of guidelines and research comparing treatment options., Methods: In this study, we retrospectively compared 78 patients who had a knee prosthetic infection within a mean follow-up period of 24 months. Group A received a soft tissue coverage in addition to orthopedic surgical therapy with or without a component replacement (CR) of the prosthesis. Group B received the same orthopedic treatment without plastic surgery for soft tissue coverage., Results: Only 21% of the patients in group A received a CR compared with 70% in group B (P = 0.0001). In group A, 83% did not have a recurrent infection, and in group B, 57% of the patients had no further infection and regained joint function (P = 0.0376). In group A, only 15% of the patients who received a CR had a significant complication within the follow-up period of 2 years, whereas in group B, 75% of patients exhibiting a major complication (P = 0.0048*)., Conclusions: Soft tissue coverage improves the outcome after PJI of the knee with soft tissue defects. Patients who simultaneously needed plastic surgery for defect coverage and orthopedic surgery for CR had the lowest number of complications overall. Based on the results of this study, a therapy algorithm could be identified considering the soft tissue defect grade leading to the lowest major complication rates and maximizing the outcome of knee prosthesis infection therapies.

The presence of a high number of macrophages within solid tumors is often significantly associated with poor prognosis and predict treatment failure for chemotherapy and radiotherapy. Macrophages are innate immune cells capable of performing diverse functions depending on the different signals from the microenvironment. The classically activated macrophage is commonly present during the early stages of tumor development while alternatively activated macrophages are associated with more advanced tumors. The distinction of the antitumoral macrophages from the pro-tumoral macrophages is not absolute. However, they have different cell surface markers such as mannose receptor (MRC1 or CD206) abundantly expressed by macrophages treated with interleukin-4 (IL-4). The important roles of macrophages in cancers suggest that it is important to develop novel therapies that target these cells. In the present study, we designed a probe using Polyamidoamine (PAMAM) fifth-generation (G5) dendrimers conjugated with mannose, Cyanine 7 (Cy7), and hydrazinonicotinamide (HYNIC) for target macrophages with high expression of MRC1 in the tumor. The intracellular uptake of 99mTc-HYNIC-dendrimer-mannose-Cy7 through the interaction with MRC1 in bone marrow-derived macrophages (BMDMs) untreated or treated with lipopolysaccharides (LPS) + interferon (IFN)γ or IL-4 was analyzed. Our results show that high-density mannose dendrimers are preferentially bound by macrophages treated by IFNγ and LPS that express lower levels of MRC1 than for macrophages treated by IL-4 that express high levels of MRC1. Furthermore, the intracellular 99mTc-HYNIC-dendrimer-mannose-Cy7 uptake in BMDMs was not inhibited in the presence of free mannose or glucose. This result suggests that 99mTc-HYNIC-dendrimer-mannose-Cy7 is not internalized via macrophage MRC1. Based on these findings, we concluded that MRC1 expression does not determine the uptake of high-density mannose dendrimers., Competing Interests: We have a conflict of interest to disclose, one of the authors, Roger Chammas is an academic editor at PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, is suggested to function in centriole elongation and conversion to centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, and reduced basal bodies in sensory organs. Rcd4 interacts with the C-terminal part of Ana3, which loads onto the procentriole during interphase, ahead of Rcd4 and before mitosis. Accordingly, depletion of Ana3 prevents Rcd4 recruitment but not vice versa. We find that neither Ana3 nor Rcd4 participates directly in the mitotic conversion of centrioles to centrosomes, but both are required to load Ana1, which is essential for such conversion. Whereas ana3 mutants are male sterile, reflecting a requirement for Ana3 for centriole development in the male germ line, rcd4 mutants are fertile and have male germ line centrioles of normal length. Thus, Rcd4 is essential in somatic cells but is not absolutely required in spermatogenesis, indicating tissue-specific roles in centriole and basal body formation., (© 2020 Panda et al.)

Accurate and reliable measurement of the electrical impedance spectrum is an essential requirement in order to draw relevant conclusions in many fields and a variety of applications; in particular, for biological processes. Even in the state-of-the-art methods developed for this purpose, the accuracy and efficacy of impedance measurements are reduced in biological systems, due to the regular occurrence of parameters causing measurement errors such as residual impedance, parasitic capacitance, generator anomalies, and so on. Recent observations have reported the necessity of decreasing such inaccuracies whenever measurements are performed in the ultra-low frequency range, as the above-mentioned errors are almost entirely absent in such cases. The current research work proposes a method which can reject the anomalies listed above when measuring in the ultra-low frequency range, facilitating data collection at the same time. To demonstrate our hypothesis, originating from the consideration of the determinant role of the measuring frequency, a physical model is proposed to examine the effectiveness of our method by measuring across the commonly used vs. ultra-low frequency ranges. Validation measurements reflect that the range of frequencies and the accuracy is much greater than in state-of-the-art methods. Using the proposed new impedance examination technique, biological system characterization can be carried out more accurately.

Background: Digital health, which encompasses the use of information and communications technology in support of health, is a key driving force behind the cultural transformation of medicine toward people-centeredness. Thus, eHealth literacy, assisted by innovative digital health solutions, may support better experiences of care., Objective: The purpose of this study is to explore the relationship between eHealth literacy and patient-reported experience measures (PREMs) among users of outpatient care in Hungary., Methods: In early 2019, we conducted a cross-sectional survey on a large representative online sample recruited from the Hungarian general population. eHealth literacy was measured with the eHealth Literacy Scale (eHEALS). PREMs with outpatient care were measured with a set of questions recommended by the Organisation for Economic Co-operation and Development (OECD) for respondents who attended outpatient visit within 12 months preceding the survey. Bivariate relationships were explored via polychoric correlation, the Kruskal-Wallis test, and chi-square test. To capture nonlinear associations, after controlling covariates, we analyzed the relationship between eHEALS quartiles and PREMs using multivariate probit, ordinary least squares, ordered logit, and logistic regression models., Results: From 1000 survey respondents, 666 individuals (364 females, 54.7%) were included in the study with mean age of 48.9 (SD 17.6) years and mean eHEALS score of 29.3 (SD 4.9). Respondents with higher eHEALS scores were more likely to understand the health care professionals' (HCPs') explanations (χ 2 9 =24.2, P=.002) and to be involved in decision making about care and treatment (χ 2 9 =18.2, P=.03). In multivariate regression, respondents with lowest (first quartile) and moderately high (third quartile) eHEALS scores differed significantly, where the latter were more likely to have an overall positive experience (P=.02) and experience fewer problems (P=.02). In addition, those respondents had better experiences in terms of how easy it was to understand the HCPs' explanations (P<.001) and being able to ask questions during their last consultation (P=.04). Patient-reported experiences of individuals with highest (fourth quartile) and lowest (first quartile) eHEALS levels did not differ significantly in any items of the PREM instrument, and neither did composite PREM scores generated from the PREM items (P>.05 in all models)., Conclusions: We demonstrated the association between eHealth literacy and PREMs. The potential patient-, physician-, and system-related factors explaining the negative experiences among people with highest levels of eHealth literacy warrant further investigation, which may contribute to the development of efficient eHealth literacy interventions. Further research is needed to establish causal relationship between eHealth literacy and patient-reported experiences., (©Zsombor Zrubka, Óscar Brito Fernandes, Petra Baji, Ottó Hajdu, Levente Kovacs, Dionne Kringos, Niek Klazinga, László Gulácsi, Valentin Brodszky, Fanni Rencz, Márta Péntek. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.08.2020.)

The Transylvanian region of Romania is a place of rich history since ancient times, where the original natural environment around architectural heritage sites or buildings has not been severely altered by urban development. Unfortunately, many such places are left by the authorities to degrade or totally collapse for lack of funds, vision or initiatives. The current paper addresses the potential of Unmanned Aerial Vehicles (UAVs) in the assessment of a viable and feasible prospect of restoration on a 19th century mansion that belonged to a nobiliary family. UAV use is rising in many industries and has become very popular in the last decade, but for survey engineering and related domains they represent a quantum leap in technology. Integrating UAV-acquired data and structure from motion software, has enabled modern techniques to obtain useful metrics from the field, accurate photorealistic 3D models for visual inspection, structural damage analyses, architectural rehabilitation-restoration, conservation and spatial analysis of the surrounding area. In this work a socio-cultural planning and design process is explored and presented to improve the local community and inclusion in a tourist circuit based on the regional potential, as well as an evaluation of accessibility derived from a vector-raster database that highlights the central position of the cultural heritage in regards to the axis of circulation between the important metropolitan areas and the local tourist attractions. This established workflow of modern topographic and construction measurements is fully integrable into the architectural process, building information modelling, heritage conservation and reconstruction.

Background: There are few studies evaluating depression, self-esteem, and mental health after gender confirming treatment of transgender women. Most of these studies include different surgical techniques and nonvalidated questionnaires. With our survey, we are aiming to assess psychopathologies and mental health as well as sexuality among a group of patients treated by the same surgeon performing our self-developed combined surgical technique. This vaginoplasty approach is characterized by constructing the vaginal cavity with parts of the penile and scrotal skin as well as the longitudinally incised urethra., Materials and Methods: Forty-seven transgender women who underwent gender confirming treatment between 2007 and 2013 were included in a retrospective study. The assessment of our study group was performed by means of self-developed indication-specific questionnaires and 3 standardized questionnaires that can be compared with norm data., Results: Preoperative psychotherapy was mostly considered as helpful by the patients, yet postoperatively, only a third of our study participants were still under therapeutic treatment. Furthermore, we could show a change in sexual preference toward a more bisexual orientation. Gender confirming treatment satisfied the expectations for most of the patients and, in their opinion, should have been performed earlier. Results of the standardized Patient Health Questionnaire 4, a short depression screening questionnaire, did not significantly differ from healthy norm data. The Freiburg Personality Inventory, Revised, revealed normal emotionality and sane self-assessment within our study group. High self-esteem and significantly higher scores than norm data were found for the Rosenberg Self-esteem Scale., Conclusions: Gender confirming treatment with the combined technique is an important part of a multi-structured treatment of transgenders and does have effects on psychological well-being. It seems to decrease psychopathologies and implicates several ameliorations for transgender women. Findings need to be verified in prospective studies including preoperative evaluations.

Background: Three-dimensional (3D) preoperative planning and assisted surgery is increasingly popular in deformity surgery and arthroplasty. Reference ranges for 3D lower limb alignment are needed as a prerequisite for standardized analysis of alignment and preoperative planning in 3D, but are not yet established., Methods: On 60 3D bone models of the lower limbs based on computed tomography data, fifteen parameters per leg were assessed by standardized validated 3D analysis. Distribution parameters and differences between sexes were evaluated. Reference values were generated by adding/subtracting one standard deviation from the mean., Results: Women had a significantly lower mean mechanical lateral distal femoral angle compared with men (86.4 ± 2.1° vs. 87.8 ± 2.0°; P < .05) and significantly lower mean joint line convergence angle (-2.5 ± 1.4° vs. -1.3 ± 1.2; P < .01), but higher mean hip knee ankle angle (178.9 ± 1.9° vs. 177.8 ± 2.3°; P < .05) and mean femoral torsion (18.2 ± 9.5° vs. 13.2 ± 6.4°; P < .05), resulting in a tendency towards valgus alignment and vice versa for men. Differences in mean medial proximal tibial angle were not significant. The mean mechanical axis deviation from the tibial knee joint center was 6.9 ± 7.3 mm medial and 1.4 ± 16.1 mm ventral without significant differences between sexes., Conclusions: We describe total and sex-related reference ranges for all alignment relevant axes and joint angles of the lower limb. There are sex-related differences in certain alignment parameters, which should be considered in analysis and surgical planning., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report. No funding was received for this study., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Spontaneous breathing trials (SBTs) are used to determine extubation readiness in extremely preterm neonates (gestational age ≤28 weeks), but these trials rely on empirical combinations of clinical events during endotracheal continuous positive airway pressure (ET-CPAP)., Objectives: To describe clinical events during ET-CPAP and to assess accuracy of comprehensive clinical event combinations in predicting successful extubation compared with clinical judgment alone., Design, Setting, and Participants: This multicenter diagnostic study used data from 259 neonates seen at 5 neonatal intensive care units from the prospective Automated Prediction of Extubation Readiness (APEX) study from September 1, 2013, through August 31, 2018. Neonates with birth weight less than 1250 g who required mechanical ventilation were eligible. Neonates deemed to be ready for extubation and who underwent ET-CPAP before extubation were included., Interventions: In the APEX study, cardiorespiratory signals were recorded during 5-minute ET-CPAP, and signs of clinical instability were monitored., Main Outcomes and Measures: Four clinical events were documented during ET-CPAP: apnea requiring stimulation, presence and cumulative durations of bradycardia and desaturation, and increased supplemental oxygen. Clinical event occurrence was assessed and compared between extubation pass and fail (defined as reintubation within 7 days). An automated algorithm was developed to generate SBT definitions using all clinical event combinations and to compute diagnostic accuracies of an SBT in predicting extubation success., Results: Of 259 neonates (139 [54%] male) with a median gestational age of 26.1 weeks (interquartile range [IQR], 24.9-27.4 weeks) and median birth weight of 830 g (IQR, 690-1019 g), 147 (57%) had at least 1 clinical event during ET-CPAP. Apneas occurred in 10% (26 of 259) of neonates, bradycardias in 19% (48), desaturations in 53% (138), and increased oxygen needs in 41% (107). Neonates with successful extubation (71% [184 of 259]) had significantly fewer clinical events (51% [93 of 184] vs 72% [54 of 75], P = .002), shorter cumulative bradycardia duration (median, 0 seconds [IQR, 0 seconds] vs 0 seconds [IQR, 0-9 seconds], P < .001), shorter cumulative desaturation duration (median, 0 seconds [IQR, 0-59 seconds] vs 25 seconds [IQR, 0-90 seconds], P = .003), and less increase in oxygen (median, 0% [IQR, 0%-6%] vs 5% [0%-18%], P < .001) compared with neonates with failed extubation. In total, 41 602 SBT definitions were generated, demonstrating sensitivities of 51% to 100% (median, 96%) and specificities of 0% to 72% (median, 22%). Youden indices for all SBTs ranged from 0 to 0.32 (median, 0.17), suggesting low accuracy. The SBT with highest Youden index defined SBT pass as having no apnea (with desaturation requiring stimulation) or increase in oxygen requirements by 15% from baseline and predicted extubation success with a sensitivity of 93% and a specificity of 39%., Conclusions and Relevance: The findings suggest that extremely preterm neonates commonly show signs of clinical instability during ET-CPAP and that the accuracy of multiple clinical event combinations to define SBTs is low. Thus, SBTs may provide little added value in the assessment of extubation readiness.

Aims: Airway and pulmonary vascular remodeling is an important pathological feature in the pathogenesis of chronic obstructive pulmonary disease (COPD). Tobacco smoke (TS) induces the production of large amounts of reactive oxygen species (ROS) in COPD lungs. We investigated how ROS lead to airway and pulmonary vascular remodeling in COPD. Results: We used in vitro bronchial and pulmonary artery smooth muscle cells (BSMCs and PASMCs), in vivo TS-induced COPD rodent models, and lung tissues of COPD patients. We found that H 2 O 2 and TS extract (TSE) induced calpain activation in BSMCs and PASMCs. Calpain activation was elevated in smooth muscle of bronchi and pulmonary arterioles in COPD patients and TS-induced COPD rodent models. Calpain inhibition attenuated H 2 O 2 - and TSE-induced collagen synthesis and proliferation of BSMCs and PASMCs. Exposure to TS causes increases in airway resistance, right ventricular systolic pressure (RVSP), and thickening of bronchi and pulmonary arteries. Calpain inhibition by smooth muscle-specific knockout of calpain and the calpain inhibitor MDL28170 attenuated increases in airway resistance, RVSP, and thickening of bronchi and pulmonary arteries. Moreover, smooth muscle-specific knockout of calpain did not reduce TS-induced emphysema in the mouse model, but MDL28170 did reduce TS-induced emphysema in the rat model. Innovation: This study provides the first evidence that ROS-induced calpain activation contributes to airway and pulmonary vascular remodeling in TS-induced COPD. Calpain might be a novel therapeutic target for the treatment of COPD. Conclusion: These results indicate that ROS-induced calpain activation contributes to airway and pulmonary vascular remodeling and pulmonary hypertension in COPD.

Rationale: Glycolytic shift is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). It remains unknown how glycolysis is increased and how increased glycolysis contributes to pulmonary vascular remodeling in PAH. Objectives: To determine whether increased glycolysis is caused by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and how PFKFB3-driven glycolysis induces vascular remodeling in PAH. Methods: PFKFB3 levels were measured in pulmonary arteries of patients and animals with PAH. Lactate levels were assessed in lungs of animals with PAH and in pulmonary artery smooth muscle cells (PASMCs). Genetic and pharmacologic approaches were used to investigate the role of PFKFB3 in PAH. Measurements and Main Results: Lactate production was elevated in lungs of PAH rodents and in platelet-derived growth factor-treated PASMCs. PFKFB3 protein was higher in pulmonary arteries of patients and rodents with PAH, in PASMCs of patients with PAH, and in platelet-derived growth factor-treated PASMCs. PFKFB3 inhibition by genetic disruption and chemical inhibitor attenuated phosphorylation/activation of extracellular signal-regulated kinase (ERK1/2) and calpain-2, and vascular remodeling in PAH rodent models, and reduced platelet-derived growth factor-induced phosphorylation/activation of ERK1/2 and calpain-2, collagen synthesis and proliferation of PASMCs. ERK1/2 inhibition attenuated phosphorylation/activation of calpain-2, and vascular remodeling in Sugen/hypoxia PAH rats, and reduced lactate-induced phosphorylation/activation of calpain-2, collagen synthesis, and proliferation of PASMCs. Calpain-2 inhibition reduced lactate-induced collagen synthesis and proliferation of PASMCs. Conclusions: Upregulated PFKFB3 mediates collagen synthesis and proliferation of PASMCs, contributing to vascular remodeling in PAH. The mechanism is through the elevation of glycolysis and lactate that results in the activation of calpain by ERK1/2-dependent phosphorylation of calpain-2.

Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coregulators of this protein. We report here that TMEM203, a conserved putative transmembrane protein, is an intracellular regulator of STING-mediated signaling. We show that TMEM203 interacts, functionally cooperates, and comigrates with STING following cell stimulation, which in turn leads to the activation of the kinase TBK1, and the IRF3 transcription factor. This induces target genes in macrophages, including IFN-β. Using Tmem203 knockout bone marrow-derived macrophages and transient knockdown of TMEM203 in human monocyte-derived macrophages, we show that TMEM203 protein is required for cGAMP-induced STING activation. Unlike STING , TMEM203 mRNA levels are elevated in T cells from patients with systemic lupus erythematosus, a disease characterized by the overexpression of type I interferons. Moreover, TMEM203 mRNA levels are associated with disease activity, as assessed by serum levels of the complement protein C3. Identification of TMEM203 sheds light into the control of STING-mediated innate immune responses, providing a potential novel mechanism for therapeutic interventions in STING-associated inflammatory diseases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Background: The authors' previous research suggested the hypothesis that aesthetic surgery in general has a positive impact on quality of life (QoL). This prospective study aimed to investigate the indication-specific effect on QoL in patients undergoing aesthetic liposuction. To our knowledge, no other prospective study has been conducted using standardised and validated questionnaires with a comparable return rate and sample size., Methods: Sixty-four patients underwent aesthetic liposuction. Forty-two patients met the inclusion criteria, and 38 of them answered one set of questionnaires preoperatively and the follow-up set at six months post-operatively. The testing instrument included a self-developed, indication-specific questionnaire and four standardised and validated questionnaires with German norm data available: Questions on Life Satisfaction, Modules (FLZ M , German version), the Freiburg Personality Inventory-Revised (FPI-R), the Rosenberg Self-Esteem Scale (RSES) and the Patient Health Questionnaire (PHQ-4)., Results: Our self-developed indication-specific questionnaire showed high satisfaction with the postoperative results. The FLZ M demonstrated significant improvements for all modules, concerning life in general (p = 0.02), health (p = 0.04) and body image (p = 0.02). Moreover, the FPI-R revealed a significant improvement in emotional stability (p < 0.01). Moreover, the PHQ-4 showed a significant reduction in overall psychological distress (p = 0.03) and anxiety (p = 0.01)., Conclusion: Liposuction had significant impact on QoL. The surgery led to a higher satisfaction not only with the result of intervention and the outer appearance specifically but also with life and the state of health generally. It improved emotional stability and reduced anxiety. Therefore, the authors' hypothesis in a previous research was confirmed for this specific indication prospectively., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Increased glycolysis in the lung vasculature has been connected to the development of pulmonary hypertension (PH). We therefore investigated whether glycolytic regulator 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFKFB3)-mediated endothelial glycolysis plays a critical role in the development of PH. Heterozygous global deficiency of Pfkfb3 protected mice from developing hypoxia-induced PH, and administration of the PFKFB3 inhibitor 3PO almost completely prevented PH in rats treated with Sugen 5416/hypoxia, indicating a causative role of PFKFB3 in the development of PH. Immunostaining of lung sections and Western blot with isolated lung endothelial cells showed a dramatic increase in PFKFB3 expression and activity in pulmonary endothelial cells of rodents and humans with PH. We generated mice that were constitutively or inducibly deficient in endothelial Pfkfb3 and found that these mice were incapable of developing PH or showed slowed PH progression. Compared with control mice, endothelial Pfkfb3 -knockout mice exhibited less severity of vascular smooth muscle cell proliferation, endothelial inflammation, and leukocyte recruitment in the lungs. In the absence of PFKFB3 , lung endothelial cells from rodents and humans with PH produced lower levels of growth factors (such as PDGFB and FGF2) and proinflammatory factors (such as CXCL12 and IL1β). This is mechanistically linked to decreased levels of HIF2A in lung ECs following PFKFB3 knockdown. Taken together, these results suggest that targeting PFKFB3 is a promising strategy for the treatment of PH., Competing Interests: The authors declare no conflict of interest.

Accuracy is the most important quality marker in medical image segmentation. However, when the task is to handle large volumes of data, the relevance of processing speed rises. In machine learning solutions the optimization of the feature set can significantly reduce the computational load. This paper presents a method for feature selection and applies it in the context of a brain tumor detection and segmentation problem in multi-spectral magnetic resonance image data. Starting from an initial set of 104 features involved in an existing ensemble learning solution that employs binary decision trees, a reduced set of features is obtained using a iterative algorithm based on a composite criterion. In each iteration, features are ranked according to the frequency of usage and the correctness of the decisions to which they contribute. Lowest ranked features are iteratively eliminated as long as the segmentation accuracy is not damaged. The final reduced set of 13 features provide the same accuracy in the whole tumor segmentation process as the initial one, but three times faster.

Background: In our previous retrospective study, we detected an increased quality of life after aesthetic abdominoplasty. In this survey, we analyzed quality of life, self-esteem, emotional stability, and mental health before and after aesthetic abdominoplasty prospectively., Methods: Twenty-two female patients were surveyed before and six months after their surgeries. The testing instrument consisted of a self-developed indication-specific questionnaire and four standardized tests (Questions on Life Satisfaction plus a specified part body image, Rosenberg Self-Esteem Scale, Freiburg Personality Inventory, and Patient Health Questionnaire-4)., Results: Significantly increased values were found concerning feeling comfortable in swimwear in front of the mirror or the sexual partner and at social or professional activities (each p=0.000). Women had less problems doing sports (p=0.029) and felt more feminine (p=0.012). Sum scores of general life satisfaction (p=0.016) and scores of the items leisure activity (p=0.003), relaxing abilities (p=0.002), and sexuality (p=0.046) showed significant improvements. The body image improved in general (p=0.010) and in particular in the items abdomen, hips, and waist (each p=0.000). Emotional stability increased significantly (p=0.029). We detected a mild mental depression in 27% and a moderate depression in 32% of our patients before surgery. Depressive disorders were significantly reduced (p=0.004) down to mild depression in 18% and moderate depression in 9% of the patients., Conclusion: Positive results for quality of life shown in the retrospective study were confirmed. Abdominoplasty improves general life satisfaction and satisfaction with health and outer appearance and increases emotional stability. Depressive patients showed a significant improvement after aesthetic abdominoplasty., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Several studies have been conducted evaluating psychological effects following aesthetic surgery, however few of them following blepharoplasty!, Purpose: To determine whether blepharoplasty affects quality of life and satisfaction as well as, emotional stability and self-esteem in patients who underwent only blepharoplasty., Design: A retrospective study including transdermal blepharoplasty operations between the years 1995 and 2008., Methods: A self-developed and indication-specific questionnaire especially for blepharoplasty, as well as the standardized testing instruments FLZM, FPI-R, and RSES, concerning quality of life, body image, personality, and self-esteem was utilized., Participants: A total of 123 patients were included in the study. Forty-six patients participated in the study., Main Outcomes and Measures: Results were compared with the existing representative norm data from the German speaking countries., Results: In the indication-specific questionnaire, 44 patients reported a positive influence on their personal wellbeing, and 33 were more satisfied with their appearance (follow-up 3-95 months; average 48.5 months); 20 felt more self-confident, and 25 felt more attractive.Statistically significant increased values in quality of life (FLZM) were found in the aspects work (P = 0.02), mobility (P < 0.001) and independence from assistance or help (P < 0.001).Higher scores concerning personality and self-esteem compared with the respective random sample were found in the questionnaires FPI-R (P = 0.02) and RSES (P < 0.001)., Conclusion and Relevance: Among plastic surgical interventions, blepharoplasty is a minimal invasive operation, which is very well tolerated by patients. Patients take advantage in personal wellbeing, self-esteem, and different aspects of their daily life.

Objective: To explore the relation between time to reintubation and death or bronchopulmonary dysplasia (BPD) in extremely preterm infants., Study Design: This was a subanalysis from an ongoing multicenter observational study. Infants with birth weight ≤1250 g, requiring mechanical ventilation, and undergoing their first elective extubation were prospectively followed throughout hospitalization. Time to reintubation was defined as the time interval between first elective extubation and reintubation. Univariate and multivariate logistic regression analyses were performed to evaluate associations between time to reintubation, using different observation windows after extubation (24-hour intervals), and death/BPD (primary outcome) or BPD among survivors (secondary outcome). aORs were computed with and without the confounding effects of cumulative mechanical ventilation duration., Results: Of 216 infants included for analysis, 103 (48%) were reintubated at least once after their first elective extubation. Reintubation was associated with lower gestational age/weight and greater morbidities compared with infants never reintubated. After adjusting for confounders, reintubation within observation windows ranging between 24 hours and 3 weeks postextubation was associated with increased odds of death/BPD (but not BPD among survivors), independent of the cumulative mechanical ventilation duration. Reintubation within 48 hours from extubation conferred higher risk-adjusted odds of death/BPD vs other observation windows., Conclusions: Although reintubation after elective extubation was independently associated with increased likelihood of death/BPD in extremely preterm infants, the greatest risk was attributable to reintubation within the first 48 hours postextubation. Prediction models capable of identifying the highest-risk infants may further improve outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Three-dimensional (3D) surgical planning and patient-specific implants are becoming increasingly popular in orthopedics and trauma surgery. In contrast to the established and standardized alignment assessment on two-dimensional (2D) long standing radiographs (LSRs) there is neither a standardized nor a validated protocol for the analysis of 3D bone models of the lower limb. This study aimed to create a prerequisite for pre-operative planning., Methods: According to 2D analysis and after meticulous research, 24 landmarks were defined on 3D bone models obtained from computed axial tomography (CT) scans for a 3D alignment assessment. Three observers with different experience levels performed the test three different times on three specimens. Intraobserver and interobserver variability of the landmarks and the intraclass correlation coefficient (ICC) of the resulting axes and joint angles were evaluated., Results: Overall, the intraobserver and interobserver variability was low, with a mean deviation <5 mm for all landmarks. The ICC of all joint angles and axis deviations was >0.8, except for tibial torsion (ICC = 0.69). All knee joint angles showed excellent ICC (>0.95)., Conclusions: Using the defined landmarks, a standardized 3D alignment assessment with low intraobserver and interobserver variability and high ICC values for the knee joint angles can be performed regardless of examiner's experience. The described method serves as a reliable standardized protocol for a 3D malalignment test of the lower limb. Three-dimensional pre-operative analysis might enhance understanding of deformities and lead to a new focus in surgical planning., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Dysregulation of adipokine secretion and action is a characteristic feature of obesity and a key clinical feature of Cushing's syndrome (CS). We have investigated whether endogenous glucocorticoid excess influences adipose tissue-derived gene expression., Material and Methods: mRNA expression of adipokines; adiponectin, resistin, tumour necrosis factor-a, interleukin-6 (IL-6), angiotensinogen (AGT), plasminogen activator inhibitor type 1, retinol binding protein 4, visfatin, and cystatin C was assessed by quantitative real-time RT-PCR in visceral adipose tissue removed during abdominal surgery of eight patients with CS, and six control patients., Results: We did not find any significant difference in the investigated genes; however, the almost significant overexpression of AGT and underexpression of IL-6 might be noteworthy (p = 0.06 in both cases)., Conclusions: No significant differences were found in the expression of the investigated genes known as cardiometabolic risk factors. This indicates that there are no major differences between endogenous hypercortisolism or diet-induced obesity regarding the expression of adipokines involved in cardiometabolic disorders. However, the difference in AGT and IL-6 expression might be included in pathways affecting fat distribution in CS.

We demonstrate that a Drosophila Golgi protein, Gorab, is present not only in the trans-Golgi but also in the centriole cartwheel where, complexed to Sas6, it is required for centriole duplication. In addition to centriole defects, flies lacking Gorab are uncoordinated due to defects in sensory cilia, which lose their nine-fold symmetry. We demonstrate the separation of centriole and Golgi functions of Drosophila Gorab in two ways: first, we have created Gorab variants that are unable to localize to trans-Golgi but can still rescue the centriole and cilia defects of gorab null flies; second, we show that expression of C-terminally tagged Gorab disrupts Golgi functions in cytokinesis of male meiosis, a dominant phenotype overcome by mutations preventing Golgi targeting. Our findings suggest that during animal evolution, a Golgi protein has arisen with a second, apparently independent, role in centriole duplication.

BackgroundThe optimal approach for reporting reintubation rates in extremely preterm infants is unknown. This study aims to longitudinally describe patterns of reintubation in this population over a broad range of observation windows following extubation.MethodsTiming and reasons for reintubation following a first planned extubation were collected from infants with birth weight ≤1,250 g. An algorithm was generated to discriminate between reintubations attributable to respiratory and non-respiratory causes. Frequency and cumulative distribution curves were constructed for each category using 24 h intervals. The ability of observation windows to capture respiratory-related reintubations while limiting non-respiratory reasons was assessed using a receiver operating characteristic curve.ResultsOut of 194 infants, 91 (47%) were reintubated during hospitalization; 68% for respiratory and 32% for non-respiratory reasons. Respiratory-related reintubation rates steadily increased from 0 to 14 days post-extubation before reaching a plateau. In contrast, non-respiratory reintubations were negligible in the first post-extubation week, but became predominant after 14 days. An observation window of 7 days captured 77% of respiratory-related reintubations while only including 14% of non-respiratory cases.ConclusionReintubation patterns are highly variable and affected by the reasons for reintubation and observation window used. Ideally, reintubation rates should be reported using a cumulative distribution curve over time.