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Comparative wood anatomy is the most accepted (traditional) method for wood identification. However, there is an ongoing search for an effective method where traditional methods may be insufficient in distinguishing on the species level. Near-infrared spectroscopy (NIRS) is one of the developing methods for wood identification. Near-infrared data of Scots pine, black pine, sessile oak and Hungarian oak were collected and examined in the spectral range of 12,000–4000 cm−1 with a resolution of 4 cm−1. Data were analyzed by partial least squares discriminate analysis (PLS-DA), decision trees (DT), artificial neural networks (ANN) and support vector machines (SVM). Raw data were subjected to multiple scatter correction (MSC), standard normal variate (SNV), Savitzky–Golay for derivatives (first [FD], second [SD]) and smoothing (Sm) and combinations of these preprocessing methods (Sm + FD, Sm + SD, FD + MSC, FD + SNV). Model performance compared through test accuracies. Accuracies varied between 99–100%, 76–98% and 73–96%, for genus level, oak and pine species, respectively. PLS-DA and SVM were found the most successful models. This study revealed that it is possible to discriminate Scots pine from black pine, and sessile oak from Hungarian oak by near-infrared spectroscopy and multivariate data analysis. [ABSTRACT FROM AUTHOR]

Identification of wood species with fast, reliable and non-destructive methods is highly important for forestry and wood-related industries. Near-infrared spectra of anatomically similar pine species (Pinus sylvestris L. and Pinus nigra J.F. Arnold) were taken and analysed by partial least squared discriminant analysis (PLS-DA) for comparing the efficiency of preprocessing methods. Raw data were subjected to multiple scatter correction (MSC), standard normal variate (SNV), Savitzky–Golay for derivatives (1st and 2nd Dr) and smoothing (Sm) and combination of these preprocessing methods (1st Dr, 1st Dr + SNV, 1st Dr + MSC, Sm + 1st Dr and Sm + 2nd Dr). The success of the models was determined by the accuracies of test sets that did not participate in the calibration phase. In this study, it was determined that not all the preprocessing methods improve the model performance. Smoothing with 1st derivatives (Sm + 1st Dr) enhanced 14.3% improvement and have the best performance (95%) for classification of pine species. For understanding modelled relationship, mean spectra and selectivity ratio were used. It was found that discrimination was held by the differences at their absorption, and the most important variables for wood classification were noted around 4000–7000 cm−1. [ABSTRACT FROM AUTHOR]

Kamu örgütleri yetersiz kaynaklar ile yüksek nitelikte kamu hizmeti üretme baskısı altındaki örgütlerdir. Kamu örgütlerinde çalışma yaşamı bir yandan örgütsel ilişkileri şekillendiren dinamiklerin, diğer yandan da kamu hizmetine ilişkin genel kabul görmüş değerlerin ve inançların etkisi altındadır. Psikolojik sözleşmenin örgütsel ilişkilere ilişkin dinamikleri, kamu hizmeti güdüsünün ise kamu hizmetine ilişkin değerleri ve inançları yansıttığı söylenebilir. Bu araştırmada üniversite idari personelinin psikolojik sözleşme algılarının iş doyumlarına etkisini ve kamu hizmeti güdüsünün bu ilişkideki aracı rolünü sınamak amacıyla yordama deseni kullanılmıştır. Araştırma Burdur Mehmet Akif Ersoy Üniversitesinde görev yapan 416 memur ve sürekli işçinin katılımıyla yapılmıştır. Veri toplama araçları olarak Psikolojik Sözleşme Ölçeği, Kamu Hizmeti Güdüsü Ölçeği ve İş Doyumu Ölçeği kullanılmıştır. Araştırmanın sonuçlarına göre ilişkisel sözleşme eğiliminin iş doyumu üzerinde olumlu bir etkisinin bulunduğu, kamu hizmeti güdüsünün ise anlamlı bir aracı olmadığı belirlenmiştir. Bu sonuçlara dayalı olarak bir yandan kamu hizmet standartlarının korunmasını sağlayacak diğer yandan da çalışan-örgüt arasındaki ilişkinin, ilişkisel sözleşmenin temel öğelerini kapsayacak düzeyde nitelikli kılınması ve bireysel özellikleri göz ardı eden genel uygulamalar yerine birey odaklı uygulamalara olanak tanıyan insan kaynakları yönetimi politikalarının uygulanması önerilmiştir.

This study examined the relationship of political skills of high school teachers to their subjective career success and the moderating role of ethical awareness in this relationship. The findings demonstrated that the participants' ethical awareness and political skill scores were relatively higher than career and life satisfaction scores. Career and life satisfaction were found to increase with professional experience. Despite being a significant predictor of career satisfaction, ethical awareness had no significant effect on life satisfaction. That said, political skill was a significant predictor of both career satisfaction and life satisfaction. Moreover, ethical awareness did not moderate the effect of political skill on career and life satisfaction. Based on these findings, implementing formal methods such as the use of vision and mission statements and in-school guidelines to make the ethical provisions mentioned in the legal regulations visible in the school environment, and school administrators’ creating an ethical working climate through implementing the ethical rules fairly for all teachers and students were recommended.

This phenomenological study aims to reveal the adaptation of public and private school teachers in Turkey to distance education during the COVID-19 pandemic. Purposeful sampling was used to form a study group. The study group consisted of 30 teachers working in Istanbul. A semi-structured interview form was prepared to collect data and interviews were conducted through phone calls or online meetings. The collected data were analyzed by phenomenological analysis. According to the findings, private school teachers were found to try more to acquire alternative skills and competencies and receive online vocational training to adapt to the novel situation and school administrators’ performance demands. Participants from public schools did not get enough feedback from their students and parents about the courses they taught and were largely deprived of the support of their colleagues. For them, adaptation to distance education turned into a process carried out with individual efforts. Studies can be conducted in this direction with a view to investigating the relationship between environmental uncertainty, job security and career adaptation based on the findings of this research.

The combined effects of temperature and compression on the microstructure of solid-wood panels produced by Aspen (Populus tremula) wood were evaluated. Thermal compression was applied on aspen wood to increase the density for improving its physical and mechanical properties. The solid wood panels with dimensions of 100 mm by 500 mm by 25 mm were hot-pressed by using a laboratory hot press at a temperature of either 150 °C or 170 °C and pressure of either 1MPa or 2 MPa, respectively, for 45 min. Changes in the microstructure were detected by using a light microscope. The microscopic investigations revealed that the wood exhibited much defects in the process conditions of 170 °C / 2 MPa, and the distribution of defects were not uniform in the growth rings of the wood specimens in the two treatment groups. All defects in cell structure were quite distinct in the beginning and the last parts of the growth rings and the largest damages occurred in the fibers and vessels for the two process conditions. The results indicate that growth ring structure, vessel porosity, and cell wall thickness have a strong effect on wood behavior in various process conditions. [ABSTRACT FROM AUTHOR]

Bu çalışmada, İstanbul Büyükşehir Belediyesi Sanat ve Meslek Eğitimi Kurslarına (İSMEK) devam eden kursiyerlerin aldıkları eğitimlere ilişkin görüşlerinin ve beklentilerinin belirlenmesi amaçlanmıştır. Çalışmada nitel araştırma desenlerinden fenomenoloji deseni kullanılmıştır. Örneklem türü olarak amaçlı örnekleme yöntemi seçilmiştir. Çalışma grubunu İSMEK’in Fatih şubesindeki dil kurslarına devam eden 25 kursiyer oluşturmaktadır. Veri toplama aracı olarak görüşme yönteminden yararlanılmış ve bu doğrultuda yarı yapılandırılmış görüşme formu hazırlanmıştır. Yapılan görüşmelerden elde edilen veriler içerik analizine tabi tutulmuştur. İSMEK’in ücretsiz olması en önemli tercih nedeni olduğu tespit edilmiştir. Kurslarda verilen eğitimin kalitesi ve kursu bitirenlere verilen sertifika kursiyerlerin İSMEK’i tercih etmelerini etkileyen önemli nedenler olduğu söylenebilir. İSMEK dil kurslarının tercih edilme nedenleri arasında ise, iş bulma beklentisi, eğitim sermayesi oluşturma, kariyer hedeflerini gerçekleştirme, sahip olduğu meslekte tutunabilme gibi ekonomik nedenlerin ağırlıkta olduğu bulgusuna ulaşılmıştır. Katılımcıların büyük çoğunluğu İSMEK sertifikasının kariyerlerine katkısı olacağını düşünmektedirler. Sosyalleşme fırsatları sunmasının İSMEK’in katılımcıların kişisel yaşamlarına yaptığı en önemli katkı olduğu tespit edilmiştir.

This conceptual study examines the analogies between schools and complex adaptive systems and identifies strategies used to manage schools as complex adaptive systems. Complex adaptive systems approach, introduced by the complexity theory, requires school administrators to develop new skills and strategies to realize their agendas in an ever-changing and complexifying environment without any expectations of stability and predictability. The results indicated that in this period administrators need to have basicskills such as (a) diagnosing patterns emerging from complexity, (b) manipulating the environment by anticipating potential patterns organizations may evolve into, (c) choosing organizational structures compatible with an ever-changing and complexifying environment and (d) promoting innovation to create and manage organizational changes. Although these skills enable administrators to reduce complexity into a manageable form to some extent, stakeholders’ having a common perspective regarding their schools and environments, and executing their activities in accordance with a shared vision are required to turn these skills into complexity management strategies.

20.yüzyılda Weber’den sonra sosyal teori içinde tarihi-sosyolojik yaklaşımın enetkili isimleri arasında Parsons ve Luhmann’ı zikretmek mümkündür. Bu çalışmadaParsons ve Luhmann’ın sosyal sistem ve meşruiyet kavramlaştırmalarıtartışılarak bu kavramların tarihi-sosyolojik yaklaşım içindeki gelişim süreci betimlenmiştir.Parsons toplumun işlevsel sorunlarla mücadele şekillerine dayalı olarak sosyalsistem kavramlaştırması yaparken, Luhmann artan çevresel karmaşıklık karşısındasosyal sistemlerin karmaşıklık azaltıcı etkilerine ve otopoyiyetik değişme mekanizmalarınavurgu yapmaktadır. Parsons dengeye odaklanarak uzlaşma sürecinde etkili olançatışma ve çelişkileri değerler sistemine havale etmektedir. Luhmann iseyasal-pozitivist bir yaklaşım benimseyerek işlemlere ve işlemleri düzenleyenyasal normlara yüzeysel bir uyumun meşrulaştırıcı etkisini öne çıkarmaktadır. Meşrulaşmasürecinde etkili olan normatif tartışmaları tam olarak açıklayamamaları, heriki meşruiyet kavramlaştırması için temel zayıflık olarak görülebilir.

Background: Prepectoral breast reconstruction has become popularized with the concurrent use of acellular dermal matrix (ADM). The authors sought to compare 3-month postoperative complication rates and explantation rates for first-stage, tissue-expander-based, prepectoral breast reconstruction with and without the use of ADM., Methods: A single-institution retrospective chart review was performed to identify consecutive patients undergoing prepectoral tissue-expander-based breast reconstruction from August of 2020 to January of 2022. Chi-square tests were used to compare demographic categorical variables, and multiple variable regression models were used to identify variables associated with 3-month postoperative outcomes., Results: The authors enrolled 124 consecutive patients. Fifty-five patients (98 breasts) were included in the no-ADM cohort and 69 patients (98 breasts) were included in the ADM cohort. There were no statistically significant differences between the ADM and no-ADM cohorts with regard to 90-day postoperative outcomes. On multivariable analysis, there were no independent associations between seroma, hematoma, wound dehiscence, mastectomy skin flap necrosis, infection, unplanned return to the operating room, or explantation in the ADM and no-ADM groups after controlling for age, body mass index, history of diabetes, tobacco use, neoadjuvant chemotherapy, and postoperative radiotherapy., Conclusions: The authors' results reveal no significant differences in odds of postoperative complications, unplanned return to the operating room, or explantation between the ADM and no-ADM cohorts. More studies are needed to evaluate the safety of prepectoral, tissue expander placement without ADM., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

As prepectoral implant placement becomes widely adopted, recent studies investigating the use of acellular dermal matrix (ADM) during tissue expander placement have demonstrated no major benefit with regard to postoperative outcomes. We sought to evaluate second-stage outcomes 1 year after tissue expander exchange to implant with and without ADM. Consecutive patients who underwent prepectoral tissue expander-based breast reconstruction with and without ADM were identified. Patients were followed up for 1 year after tissue expander exchange to implant. Second-stage outcomes of interest including implant rippling, capsular contracture, implant explantation, additional revision surgeries, and patient-reported outcomes were collected and compared. Sixty-eight breasts in the ADM cohort and sixty-one breasts in the no ADM cohort underwent tissue expander exchange to implant. Second-stage outcomes of interest were similar between the ADM and no ADM cohorts with no statistically significant differences identified regarding incidences of implant rippling (24.6% vs. 12.1%, p = 0.08), capsular contracture (4.5% vs. 3.3%, p = 1.00), and explantation (6.6% vs. 1.7%, p = 0.67) between the two cohorts. BREAST-Q scores were similar between the two cohorts with the exception of physical wellbeing and satisfaction in terms of implant rippling, as can be seen, which improved in the no ADM cohort (p = 0.04). Our study reports no major benefit for the inclusion of ADM with respect to implant rippling, capsular contracture, explantation, need for additional revision surgeries, and patient-reported satisfaction in prepectoral second-stage implant-based breast reconstruction., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Accumulation of excessive extracellular matrix (ECM) components from lung fibroblasts is a feature of systemic sclerosis-associated interstitial lung disease (SSc-ILD), and there is increasing evidence that innate immune signaling pathways contribute to these processes. Toll-like receptors (TLRs) are innate immune sensors activated by danger signals derived from pathogens or host molecular patterns. Several damage-associated molecular pattern (DAMP) molecules are elevated in SSc-ILD plasma, including ligands that activate TLR9, an innate immune sensor recently implicated in driving profibrotic responses in fibroblasts. Fibronectin and the isoform fibronectin-extra domain A (FN-EDA) are prominent in pathological extracellular matrix accumulation, but mechanisms promoting FN-EDA accumulation are only partially understood. Here, we show that TLR9 activation increases FN-EDA accumulation in MRC5 and SSc-ILD fibroblasts, but that this effect is independent of changes in FN-EDA gene transcription. Rather, we describe a novel mechanism where TLR9 activation inhibits FN-EDA turnover via reduced FN-EDA ubiquitination. TLR9 ligand ODN2006 reduces ubiquitinated FN-EDA destined for lysosomal degradation, an effect abrogated with TLR9 knockdown or inhibition. Taken together, these results provide rationale for disrupting the TLR9 signaling axis or FN-EDA degradation pathways to reduce FN-EDA accumulation in SSc-ILD fibroblasts. More broadly, enhancing intracellular degradation of ECM components through TLR9 inhibition or enhanced ECM turnover could be a novel strategy to attenuate pathogenic ECM accumulation in SSc-ILD.

Takayasu arteritis (TA) is a large-cell vasculitis, and is not usually associated with avascular necrosis (AVN). The objective of the study was to investigate any association between TA and AVN, including the possible pathogenic effect of glucocorticoid (GCs) use. The study design was retrospective and cross sectional. TA patients were enrolled in the study. Demographic variables, disease activity, treatments, physician global assessment, Indian Takayasu Clinical activity score 2010, and Kerr criteria were recorded. Logistic regression analysis was performed to identify predictors of AVN. A total of 29 patients were assessed. AVN was observed in four (13.8%) patients with TA. Male gender and elevated C-reactive protein (CRP) were found to be significantly associated with AVN (p = 0.001 and p = 0.006, respectively). While type IIb TA was more common in patients with AVN (n = 2, 50%), type V was more likely in the absence of AVN (n = 13, 52%). Descending aorta and thoracic aorta were usually involved in patients with AVN (both, n = 3, 75%). In multivariate logistic regression, increased CRP levels were the only predictor for AVN (OR = 1.183, 95% Cl = 1.025-1.364, p = 0.021). No association was identified between AVN in TA patients and either duration or cumulative dose of GCs. The present study found that higher CRP levels and male gender were associated with AVN in patients with TA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aquaporin 5 (AQP5) is expressed in several cell types in the lung and regulates water transport, which contributes to barrier function during injury and the composition of glandular secretions. Reduced AQP5 expression is associated with barrier dysfunction during acute lung injury, and strategies to enhance its expression are associated with favorable phenotypes. Thus, pharmacologically enhancing AQP5 expression could be beneficial. Here, we optimized a high-throughput assay designed to detect AQP5 abundance using a cell line stably expressing bioluminescent-tagged AQP5. We then screened a library of 1153 compounds composed of FDA-approved drugs for their effects on AQP5 abundance. We show compounds Niclosamide, Panobinostat, and Candesartan Celexitil increased AQP5 abundance, and show that Niclosamide has favorable cellular toxicity profiles. We determine that AQP5 levels are regulated in part by ubiquitination and proteasomal degradation in lung epithelial cells, and mechanistically Niclosamide increases AQP5 levels by reducing AQP5 ubiquitination and proteasomal degradation. Functionally, Niclosamide stabilized AQP5 levels in response to hypotonic stress, a stimulus known to reduce AQP5 levels. In complementary assays, Niclosamide increased endogenous AQP5 in both A549 cells and in primary, polarized human bronchial epithelial cells compared to control-treated cells. Further, we measured rapid cell volume changes in A549 cells in response to osmotic stress, an effect controlled by aquaporin channels. Niclosamide-treated A549 cell volume changes occurred more rapidly compared to control-treated cells, suggesting that increased Niclosamide-mediated increases in AQP5 expression affects functional water transport. Taken together, we describe a strategy to identify repurposed compounds for their effect on AQP5 protein abundance. We validated the effects of Niclosamide on endogenous AQP5 levels and in regulating cell-volume changes in response to tonicity changes. Our findings highlight a unique approach to screen for drug effects on protein abundance, and our workflow can be applied broadly to study compound effects on protein abundance in lung epithelial cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Villandre, White, Lear, Chen, Tuncer, Vaiz, Tuncer, Lockwood, Camarco, Liu, Chen and Evankovich.)

Aims: Sepsis causes life-threatening tissue and organ dysfunctions caused by endogenous mediators in response to infection. Melatonin is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. This study aimed to evaluate the changes in serum and liver tissue levels of VEGF, TGF-β and MMP-2 in melatonin-treated septic rats., Materials and Methods: Twenty-one Wistar-albino male rats were included in this study. Rats were randomly divided into three groups. Group 1 is sham-operated control (C) group, Group 2 is caecal ligation and puncture (CLP) group and Group 3 is melatonin-treated (10 mg/kg) (M-CLP) group. Serum and tissue samples were analysed. All procedures were carried out according to the ethical rules specified in Helsinki Declaration., Results: Sera MMP-2 levels were found higher than tissue MMP-2 levels in C and CLP (respectively, P = .048, P = .01). In CLP and M-CLP, serum TGF-β levels were higher than tissue TGF-β levels(respectively, P = .05, P = .01). Serum VEGF levels in CLP were found to be significantly higher than both C and M-CLP(P < .01)., Conclusion: MMP-2 levels may have increased because of the prevention of oxidative damage in sepsis, and this may increase the anti-inflammatory effect. Melatonin treatment may have a therapeutic effect against sepsis since it prevents the increase in serum VEGF level. A powerful endogenous antioxidant, may be a promising therapeutic agent on the mortality and morbidity of the disease, because of its lowering effect on serum VEGF, which is a poor prognostic factor in sepsis., (© 2021 John Wiley & Sons Ltd.)

SARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.

The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin. This compound increases the biological activity of Ampk not by stimulating the activation of Ampk, but rather by preventing activated pAmpkα from Fbxo48-mediated degradation. We demonstrate that, consistent with augmenting Ampk activity, BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity in high-fat-diet-induced obese mice. Hence, we provide a unique bioactive compound that inhibits pAmpkα disposal. Together, these results define a new pathway regulating Ampk biological activity and demonstrate the potential utility of modulating this pathway for therapeutic benefit.

NRF2 is a master regulator of cellular anti-oxidant and anti-inflammatory responses, and strategies to augment NRF2-dependent responses may beneficial in many diseases. Basal NRF2 protein level is constrained by constitutive KEAP1-mediated degradation, but in the presence of electrophiles, NRF2 ubiquitination is inhibited. Impeded NRF2 degradation increases NRF2 protein, resulting in up-regulation of anti-oxidant gene transcription, and decreased inflammation. KEAP1-independent mechanisms regulating NRF2 stability have also been reported. Here we employed an HTS approach and identified a small molecule, BC-1901S, that stabilized NRF2 and increased its activity. BC-1901S activated NRF2 by inhibiting NRF2 ubiquitination in a KEAP1-independent manner. It further increased NRF2-dependent anti-oxidant gene transcription, and exhibited anti-inflammatory effects in vitro and in vivo. Further, we identified a new NRF2-interacting partner, DDB1 and CUL4 Associated Factor 1 (DCAF1), an E3 ligase that targeted NRF2 for proteasomal degradation. Mechanistically, BC-1901S directly bound to DCAF1 and disrupted NRF2/DCAF1 interaction, thus activating NRF2. These findings provide new insights in NRF2 biology and NRF2 based anti-inflammatory therapy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Systemic scleroderma (SSc) is an autoimmune disease that affects over 2.5 million people globally. SSc results in dysfunctional connective tissues with excessive profibrotic signaling, affecting skin, cardiovascular, and particularly lung tissue. Over three-quarters of individuals with SSc develop pulmonary fibrosis within 5 years, the main cause of SSc mortality. No approved medicines to manage lung SSc currently exist. Recent research suggests that profibrotic signaling by transforming growth factor β (TGF-β) is directly tied to SSc. Previous studies have also shown that ubiquitin E3 ligases potently control TGF-β signaling through targeted degradation of key regulatory proteins; however, the roles of these ligases in SSc-TGF-β signaling remain unclear. Here we utilized primary SSc patient lung cells for high-throughput screening of TGF-β signaling via high-content imaging of nuclear translocation of the profibrotic transcription factor SMAD family member 2/3 (SMAD2/3). We screened an RNAi library targeting ubiquitin E3 ligases and observed that knockdown of the E3 ligase Kelch-like protein 42 (KLHL42) impairs TGF-β-dependent profibrotic signaling. KLHL42 knockdown reduced fibrotic tissue production and decreased TGF-β-mediated SMAD activation. Using unbiased ubiquitin proteomics, we identified phosphatase 2 regulatory subunit B'ϵ (PPP2R5ϵ) as a KLHL42 substrate. Mechanistic experiments validated ubiquitin-mediated control of PPP2R5ϵ stability through KLHL42. PPP2R5ϵ knockdown exacerbated TGF-β-mediated profibrotic signaling, indicating a role of PPP2R5ϵ in SSc. Our findings indicate that the KLHL42-PPP2R5ϵ axis controls profibrotic signaling in SSc lung fibroblasts. We propose that future studies could investigate whether chemical inhibition of KLHL42 may ameliorate profibrotic signaling in SSc., (© 2020 Lear et al.)

Nonsteroidal anti-inflammatory drugs have been used as part of multimodal postoperative analgesic regimens to reduce the necessity of opioids. However, due to its effect on platelet function, there is a hesitation to utilize ketorolac postoperatively. The goal of this study is to analyze our experience utilizing ketorolac in patients who underwent major cranial vault remodeling (CVR) for craniosynostosis with an emphasis on postoperative hemorrhage and complications., Methods: A retrospective review was performed for all patients undergoing CVR for craniosynostosis from 2013 to 2017. Primary outcomes were hemorrhagic complications. Secondary outcomes included length of stay, emesis, and doses of pain medication., Results: Seventy-four consecutive patients met inclusion criteria. Forty-three (58.1%) received ketorolac. Seven in the ketorolac group (16%) and 9 in the control group (29%) received intraoperative blood transfusion ( P = 0.25). One in the ketorolac group (2.3%) and 2 in the control group (3.1%) necessitated postoperative transfusion ( P = 0.56). Patients who received ketorolac required less morphine doses (2.1 versus 3.3 doses; P = 0.02) and had a reduced length of stay (2.1 versus 2.6 nights; P = 0.04)., Conclusions: This is the first study to demonstrate that postoperative ketorolac is not associated with an increase in hemorrhagic complications or transfusion risk in children who underwent CVR for craniosynostosis. Patients administered ketorolac required less morphine and had a hospital length of stay. We hope this study stimulates more well-done prospective trials analyzing the role that ketorolac can play in an effective and safe postoperative analgesia regimen., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

L-2 hydroxyglutaric aciduria (L2HGA) is a rare, infantile-onset, autosomal recessive organic aciduria affecting exclusively the central nervous system. A case is reported here of L2HGA presenting with macrocephaly and febrile seizure. Although there have been reports of epilepsy associated with L2HGA, to the best of our knowledge this is the second case in literature of febrile seizure in a patient with L2HGA. This report suggests that detailed neurological evaluation of macrocephalic children with febrile convulsion is important. Moreover, metabolic and genetic investigations may be necessary for these kinds of patients.

Purpose: In a recent genome-wide association study for partial epilepsies in the European population, a common genetic variation has been reported to affect partial epilepsy only modestly. However, in complex diseases such as partial epilepsy, multiple factors (e.g. single nucleotide polymorphisms, microRNAs, metabolic and epigenetic factors) may target different sets of genes in the same pathway, affecting its function and thus causing the disease development. In this regard, we hypothesize that the pathways are critical for elucidating the mechanisms underlying partial epilepsy., Methods: Previously we had developed a novel methodology with the aim of identifying the disease-related pathways. We had combined evidence of genetic association with current knowledge of (i) biochemical pathways, (ii) protein-protein interaction networks, and (iii) the functional information of selected single nucleotide polymorphisms. In our present study, we apply this methodology to a data set on partial epilepsy, including 3445 cases and 6935 controls of European ancestry., Results: We have identified 30 overrepresented pathways with corrected p-values smaller than 10(-12). These pathways include complement and coagulation cascades, cell cycle, focal adhesion, extra cellular matrix-receptor interaction, JAK-STAT signaling pathway, MAPK signaling pathway, proteasome, ribosome, calcium signaling and regulation of actin cytoskeleton pathways. Most of these pathways have growing scientific support in the literature as being associated with partial epilepsy. We also demonstrate that different factors affect distinct parts of the pathways, as shown here on complement and coagulation cascades pathway with a comparison of gene expression vs. genome-wide association study., Conclusions: Traditional studies on genome-wide association have not revealed strong associations in epilepsies, since these single nucleotide polymorphisms are not shared by most of the patients. Our results suggest that it is more effective to incorporate the functional effect of a single nucleotide polymorphism on the gene product, protein-protein interaction networks and functional enrichment tools into genome-wide association studies. These can then be used to determine leading molecular pathways, which cannot be detected through traditional analyses. We hope that this type of analysis brings the research community one step closer to unraveling the complex genetic structure of epilepsies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To investigate the occurrence of MDR1 C3435T gene polymorphisms in the Turkish renal transplant patients treated with cyclosporine (CsA), and correlate these findings with prevalence and degree of gingival hyperplasia (GH)., Methods: Before to renal transplantation, dental treatment and oral hygiene education of 300 renal disease patients was completed. Peripheral blood samples were collected from 154 renal transplant recipients on CsA treatment without calcium channel blockers. MDR1 C3435T gene polymorphism and GH were analyzed at posttransplant month 6., Results: No difference was detected among groups for age, posttransplant period, creatine levels, serum concentration of CsA, or plaque and bleeding indices (P > .05). Out of all transplanted patients, 42.8% were found to have the heterozygote genotype. This was reduced to 37.5% when individuals with GH were taken into account. However, when degree of GH was analyzed, those with severe GH were found to have the heterozygote genotype significantly more often (P < .05)., Conclusions: The MDR1 gene polymorphism is not associated with GH frequency, but may be associated with GH severity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The duodenum and gastrointestinal tract are rarely involved by multiple myeloma, either diffusely or as a focal mass. A 59-year-old man was diagnosed with multiple myeloma and given chemotherapy. Four months later, he developed jaundice. Gastroduodenal plasmacytoma causing extrahepatic biliary obstruction was diagnosed. To the best of our knowledge, this case is the first report of gastroduodenal plasmacytoma presenting with biliary obstruction.