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Bu çalışmada, perlit (PT) ve uçucu kül (UK) bazlı geopolimerlere çömlek sırı atığı (ÇSA) ikamesinin mekanik özellikler ve yüksek sıcaklık performansı üzerindeki etkisi araştırılmıştır. Sadece PT, sadece UK ve ağırlıkça %75 UK ve %25 PT içeriği ile üretilen geopolimer harçlara %10, 20 ve 30 oranlarında ÇSA ikame edilmiştir. Harçlar, sabit 10M NaOH içeriği ve 8 saat 100 ºC ısıl kür ile üretilmiştir. Üretilen harçların 7, 28 ve 90 günlük eğilme ve basınç dayanımları belirlenmiş ve 500 ºC, 750 ºC ve 1000 ºC sıcaklıklarındaki performansları değerlendirilmiştir. Deneyler sonucunda, ÇSA malzemesinin PT ve UK+PT içeren numunelere kütlece %20 oranına kadar ikame edilmesinin nihai basınç dayanımı açısından olumlu yönde etkileri olduğu, UK içeren numunelerde ise ÇSA ikamesinin nihai basınç dayanımı açısından olumsuz etkileri olduğu tespit edilmiştir. Nihai dayanımlarda en yüksek değerler, 34.4 ve 32.41 MPa basınç ve 6.46 ve 6.3 MPa eğilme dayanımları ile UK+PT+ÇSA içeren numunelerde sırasıyla %10 ve 20 ÇSA oranlarında elde edilmiştir. Eğilme ve basınç dayanımları açısından optimum ÇSA oranının %10-20 aralığında olduğu söylenebilir. UK malzemesine ÇSA malzemesinin ikamesi, kür yaşına göre dayanım gelişimlerini olumsuz etkilerken, PT ve UK+PT içeren numunelere ÇSA malzemesi ikamesi dayanım gelişimlerinde olumlu etkiler meydana getirmiştir. ÇSA malzemesi yüksek sıcaklık performansı açısından tüm gruplarda olumlu etki meydana getirmiştir. ÇSA malzemesinin karışımlarda kütlece ikame yüzdesi arttıkça, dayanım kayıpları azalmıştır. UK malzemesinin yerine %30 ÇSA malzemesinin ikame edildiği numunelerde 750 ºC’de %40’a varan dayanım artışı tespit edilmiştir.

Background Tennis requires movement abilities in changing playing situations. This article investigates the relationship between lower extremity strength asymmetry ratio and linear and multidimensional running performances in female tennis players. Methods A total of 56 female tennis players, with a mean age of 15.44 ± 0.50 years, participated in the study—the research design involved three sessions at 48-hour intervals. In the first session, athletes performed dominant and non-dominant countermovement jump (CMJ) and board jump (BJ) tests. The second (sec) session included 10-meter (−m) and 30-m linear running performance tests, while the final session assessed multidimensional running performance with a change of direction (COD) test. The relationship between CMJ and BJ asymmetry ratios and linear and multidimensional running performances was analysed using the Pearson correlation coefficient. Bilateral asymmetry rates in linear and multidimensional running performance were determined through linear regression analysis. Results The dominant CMJ recorded 17.56 ± 3.47 cm, while BJ was 130.23 ± 21.76 cm, and the non-dominant CMJ measured 16.79 ± 4.51 cm with a BJ of 147.52 ± 30.97 cm. The athletes had a CMJ asymmetry rate of 12.67 ± 11.29% and a BJ asymmetry rate of 7.19 ± 5.28%. A relationship was seen between the CMJ asymmetry rate and 30-m running performance (r = 0.368, p

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Seramik sırlarında, renk ve estetik etkileri artırmak amacıyla atık malzemelerin kullanımı önemli bir araştırma alanıdır. Bu atıkların seramik sırlarında renklendirici olarak potansiyel kullanımı, sürdürülebilirlik ve geri dönüşüm açısından büyük öneme sahiptir. Bu çalışmada, yer karosu mat sırlarında bazalt kesim atığı ilavesinin renk, faz ve mikroyapı üzerindeki etkisi araştırılmıştır. Bazalt kesim atığının kimyasal, faz ve tane boyut analizi ile karakterizasyonu yapılmış ve ağ. %1-9 oranında bazalt kesim atığının endüstriyel karo mat sırına eklenmesiyle, sırlar beyazdan açık kahve bej tonlarına dönüşmüş ve yüzeylerde benekli bir yapı oluşmuştur. Bazalt kesim atığının sır bünyesine ilavesinde direkt kullanımının yanı sıra 900-1100°C aralığında farklı sıcaklıklarda kalsinasyonu sonrasında kullanımı sonucu sır yapısında anortit, kristobalit ve diopsit fazları tespit edilmiştir. Standart mat sır ve ağ. %9 oranında atık (BKA) içeren mat sırlı yer karolarının mikroyapı analizlerinde (SEM/EDS) anortit kristalleri ve Ca, Fe içeriğinin arttığı tespit edilmiştir. Bu çalışma sonucunda, yer karosu mat sırlarının bej tonlarında bazalt atığıyla renklendirilmesinin, ekonomik açıdan avantaj sağlayabileceği ve atığın geri dönüşümüne katkıda bulunabileceği, sır üretiminde potansiyel bir renklendirici olarak kullanılabileceği sonucuna varılmıştır.

IntroductionChronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation.Methods40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling.ResultsChronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset.ConclusionAgainst the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

Introduction Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.Trial registration number NCT06087952.

ABSTRACT Objective: In this study, we aimed to evaluate the factors affecting major adverse event (MAE) development after full-term neonatal cardiac surgery. Methods: This study was conducted retrospectively on newborns who underwent congenital heart surgery between June 1, 2020, and June 1, 2022. MAE was defined as the presence of at least one of the following: cardiac arrest, unplanned reoperation, emergency chest opening, admission to the advanced life support system, and death. The role of blood lactate level, vasoactive inotropic score (VIS), and cerebral near-infrared spectroscopy (NIRS) changes in predicting MAE was investigated. Results: A total of 240 patients (50% male) were operated during the study period. The median age of patients was seven days (interquartile range 3-10 days). MAE was detected in 19.5% of the cases. Peak blood lactate levels >7 mmol/liter (area under the curve [AUC] 0.72, 95% confidence interval [CI] [0.62-0.82], P 10 was an independent risk factor (AUC 0.75, 95% CI [0.70-0.84], P 30%, high blood lactate levels, and VIS score within the 48 hours may help to predict the development of MAE in the postoperative period.

The Phasor Measurement Unit (PMU) is a modern measuring device built on the system for monitoring, controlling, and protecting power systems. Since the costs of PMU devices are very high, they must be placed in the system in optimum numbers and in a way that monitors the whole system. This study determined the locations and numbers of the optimal number of PMU devices that can monitor the whole system. Integer Linear Programming (ILP) and Binary Particle Swarm Optimization (BPSO) methods are proposed to solve the optimum PMU placement (OPP) problem. Then, the solution to the problem is carried out using Dragonfly Algorithm (DA), which is proposed as a new heuristic method. Solution methods were applied to the IEEE 14-Bus Test System and Türkiye 400 kV Interconnected Power System, and the results were compared. In addition, the results of the proposed methods were compared with the results of different studies in the literature. Thanks to the ILP, BPSO, and DA methods proposed in this study, it has been determined that power systems can be observed with fewer PMU devices. The DA method offers a great cost advantage as it is the method that provides a solution with 5 fewer PMU devices for the 400 kV Interconnected Power System in Türkiye.

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%–5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc+/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc+/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.

The objective of this study is to determine how much candidate teachers have utilized internet forums while deciding their university to study. This is a study in survey model. The population of the study consists of freshmen students studying at Usak University's Faculty of Education in 2014-2015 academic year (400 students). The scale has been distributed to the entire population, while 267 of them have been returned and 251 of them have been evaluated. "Virtual Forum Utilization during University Decision Period" scale has been developed by the researchers. The initial scale consisting of 14 items has been applied to 150 students and two items with low factor load have been dismissed. The renewed 12 item scale has been re-applied to the students. Cronbach-Alpha internal consistency coefficient of the scale has been calculated as 0.825. Validity of the scale has been tested by exploratory and confirmatory factor analyses and KMO value of the scale has been calculated as 0.811. According to the confirmatory factor analysis, the scale consists of seven items and its fit index value has proved to be acceptable. 94% of the candidate teachers have memberships at student forums, while 89% of them get online at these forums several times a day. 42% of the teacher candidates utilize these forums to follow current affairs. Candidate teachers have reported that they had frequently visited student forums while they were about to decide their university to study. Independent groups "t test" has yielded that there is no significant difference between the forum utilization levels of female and male candidate teachers. One way variance analysis has shown that candidate teachers at social sciences teaching department utilize student forums more than other departments.

Abstract Background and aim Pathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache. Methods This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied. Results The mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. Conclusion Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.

Introduction: Although cancer patients have a high risk of exposing COVID-19 and developing severe complications, they have to receive active treatment. We aimed to determine the psychological conditions of cancer patients and shed light on the establishment of early psychological intervention and intervention policies by making specific recommendations. Method: We consecutively evaluated 385 cancer patients under treatment. Post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, stress, and associated sociodemographic/clinical characteristics were investigated. In addition, we applied depression-anxiety-stress-scale-21 (DASS-21) for the mental states of patients and Impact of Event-Scale-Revised (IES-R) for the psychological effects of Covid-19. Results: The mean age was 58 (18–88). 47.2% were psychologically distressful per DASS-21, and 39.3% were traumatic per IES-R scores. 71.9% stated the risk of getting COVID-19 was high since they had cancer, and 82% stated serious complications would develop if they had COVID-19 infection. Patients diagnosed for more than one year were more stressed, anxious, and depressive (p–value = 0.001,0.003,0.049, respectively). Singles were more stressed, depressed, and traumatized than couples (p-value = 0.001, 0.011, 0.001). In multivariate analysis, a significant correlation with being under psychiatric treatment before the pandemic was found for depression (OR: 3.743, 95 %CI: 1.790–7.827) anxiety (OR: 3.776–95 %CI: 1.945–7.332) and stress levels (OR: 4.129, 95 %CI: 1.728–9.866). Having relatives who died or received treatment for COVID-19(OR: 0.515,0.296–0.895) and being unmarried (OR: 2.445–95% CI: 1.260–4.747) predicts PTSD development. Conclusions: When the psychological effects of the COVID-19 pandemic are manifesting strongly, cancer patients' anxiety and exposure levels are high. It is of great importance that clinicians understand needs, recognize psychological distress, and direct them to relevant departments for supportive care.

IntroductionIn the last decades, we have seen a rapid increase in the prevalence of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergies. The environmental changes caused by industrialization, urbanization and modernization, including dramatic increases in air pollutants such as particulate matter (PM), diesel exhaust, nitrogen dioxide (NO2), ozone (O3), alarming effects of global warming, change and loss of biodiversity, affect both human health and the entire ecosystem.ObjectiveIn this review, we aimed to discuss the effects of the external exposome on epithelial barriers and its relationship with the development of allergic diseases by considering the changes in all stakeholders of the outer exposome together, in the light of the recently proposed epithelial barrier hypothesis.MethodTo reach current, prominent, and comprehensive studies on the subject, PubMed databases were searched. We included the more resounding articles with reliable and strong results.ResultsExposure to altered environmental factors such as increased pollution, microplastics, nanoparticles, tobacco smoke, food emulsifiers, detergents, and household cleaners, and climate change, loss and change in microbial biodiversity, modifications in the consumption of dietary fatty acids, the use of emulsifiers, preservatives and the decrease in the antioxidant content of the widely consumed western diet may disrupt the epithelial barriers of the skin, respiratory and gastrointestinal tracts, making us more vulnerable to exogeneous allergens and microbes. Epithelial cell activation, microbial dysbiosis and bacterial translocation disrupt the immune balance and a chronic Th2 inflammation ensues.ConclusionDramatic increases in air pollution, worrisome effects of global warming, dysbiosis, changing dietary habits and the complex interactions of all these factors affect the epithelial barriers and local and systemic inflammation. We want to draw attention to the emerging health effects of environmental changes and to motivate the public to influence government policies for the well-being of humans and the nature of the earth and the well-being of future generations.

Abstract Background MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. Methods This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. Results The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p

Abstract Background To emphasize the importance of CT in the diagnosis of COVID-19 disease by comparing the thoracic CT findings of COVID-19 patients with positive RT-PCR results and patients with clinical suspicion of COVID-19 but with negative RT-PCR results. Results In our study, COVID-19 patients with positive RT-PCR results (RT-PCR (+) group) and patients with clinical suspicion of COVID-19 but negative RT-PCR results (RT-PCR (−) group) were compared in terms of CT findings. In CT images, ground-glass opacity and ground-glass opacity + patchy consolidation were the most common lesion patterns in both groups. No statistically significant differences in the rates and types of lesion patterns were observed between the two groups. In both groups, lesion distributions and distribution patterns were similarly frequent in the bilateral, peripheral, and lower lobe distributions. Among the 39 patients who underwent follow-up CT imaging in the first or second month, a regression in lesion number and density was detected in 18 patients from both groups. Consolidations were completely resorbed in 16 of these patients, and five patients had newly developed fibrotic changes. The follow-up CT examination of 16 patients was normal. Conclusions Due to the false-negative rate of RT-PCR tests caused by various reasons, clinically suspected COVID-19 patients with a contact history should be examined with CT scans, even if RT-PCR tests are negative. If the CT findings are positive, these patients should not be removed from isolation.

Peppermint (Mentha x piperita L.) plant was grown in this study using different mineral fertilizers combinations. Effects of fertilizer treatments on green and drug herb yields, herb essential nutrients (N, P, K, Ca, Na, Mg, Fe, Zn, Mn, Cu), essential oil yield, essential oil components (menthol, menthone, 1,8 cineole and menthofuran) and non-essential elements (heavy metal) (Pb, Ni, Co, Cr and Cd) were determined in two successive years (2011-2012). The highest green and drug herb yields were obtained from mono ammonium phosphate (MAP) treatments (24,980 kg ha–1 and 3070 kg ha–1) in the first year and from 15:15:15 treatments (16,950 kg ha–1 and 3080 kg ha–1) in the second year. Nutrient elements nitrogen 2.70% in MAP application, phosphorus 0.55% in mono potassium phosphate (MKP) application, potassium 3.12% in MAP application, calcium 1.47% in di ammonium phosphate (DAP) application, magnesium 0.36% in 15:15:15 application, iron 106 mg kg–1 in 15:15:15 application, copper 11.83 mg kg–1 in MAP application, zinc 35 mg kg–1 in MKP application and manganese 89 mg kg–1 in MAP application the highest value were respectively obtained from treatments. Concentrations of non-essential elements (Pb, Ni, Cr and Cd) in herb were found to be below toxic values. In both years, the highest essential oil yields were obtained from MAP treatments (4.10% in the first year and 2.90% in the second year). The essential oil components of peppermint were menthol, menthone, 1,8 cineole and menthofuran and menthol was the major component in both years. Highlights - Nitrogen fertilizer applications increased herb yield. - In terms of plant nutrients, mono ammonium phosphate and 15:15:15 fertilizers were more effective than other fertilizer applications. - Heavy metal concentrations of peppermint herb were determined below the limit values. - The main compound in peppermint essential oils was menthol in both years.

Aim:Migraine is a multifaceted neurological disease whose molecular mechanisms are not yet clearly defined. Oxidative stress is also believed to play a role in the pathogenesis of migraine. The purpose of this study was to evaluate serum paraoxonase (PON) and arylesterase (ARE) activities, thiols levels, ischemia-modified albumin (IMA), the total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) in patients with migraine without aura.Materials and Methods:30 patients (5 males and 25 females) and 30 matched healthy controls (8 males and 22 females) were enrolled. Serum PON and ARE activities, thiols levels, IMA, TAS, TOS and OSI were determined by using the spectrophotometric method in the study groups. Statistical analysis was conducted using Mann–Whitney U test and independent samples t-test, and p

X-linked retinoschisis, a disease characterized by splitting of the retina, is caused by mutations in the retinoschisin gene, which encodes a putative secreted cell adhesion protein. Currently, there is no effective treatment for retinoschisis, though viral vector-mediated gene replacement therapies offer promise. We used intravitreal delivery of three different AAV vectors to target delivery of the RS1 gene to Müller glia, photoreceptors or multiple cell types throughout the retina. Müller glia radially span the entire retina, are accessible from the vitreous, and remain intact throughout progression of the disease. However, photoreceptors, not glia, normally secrete retinoschisin. We compared the efficacy of rescue mediated by retinoschisin secretion from these specific subtypes of retinal cells in the Rs1h-/- mouse model of retinoschisis. Our results indicate that all three vectors deliver the RS1 gene, and that several cell types can secrete retinoschisin, leading to transport of the protein across the retina. The greatest long-term rescue was observed when photoreceptors produce retinoschisin. Similar rescue was observed with photoreceptor-specific or generalized expression, although photoreceptor secretion may contribute to rescue in the latter case. These results collectively point to the importance of cell targeting and appropriate vector choice in the success of retinal gene therapies.

An environmentally friendly unreported rapid and simple reverse-phase high-performance thin-layer chromatography (RP-HPTLC) has been designed for the simultaneous determination of bioactive sesquiterpene coumarins feselol and samarcandin in the methanol extract of five Ferula species. The method was developed using glass plates coated with RP-18 silica gel 60 F254S and a green solvent system of ethanol–water mixture (8:2 v/v) as mobile phase. After development, the plates were quantified densitometrically at 254 for feselol and samarcandin. Feselol and samarcandin peaks from methanol extract of five Ferula species were identified by comparing their single band at Rf = 0.43 ± 0.02 and Rf = 0.60 ± 0.01, respectively. Valid linear relationships between the peak areas and concentrations of feselol and samarcandin in the range of 1000–7000 ng/band respectively were obtained. The method was subjected to the validation criteria of the international conference on harmonization (ICH) for precision, accuracy, and robustness. The new method provides an analytical tool to enumerate the therapeutic doses of feselol and samarcandin in herbal formulations and/or crude drugs. The obtained results indicated that F. drudeana was the richest species in the more active samarcandin, with 0.573% w/w, while F. duranii had the largest quantity of the less active feselol, 0.813% w/w. F. drudeana was superior to the other species in the sum of the two active compounds, 1.4552% w/w, and was consequently expected to be the most active aphrodisiac among the five studied species.

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

Optimizing protein intake is a novel strategy to prevent age associated loss of muscle mass and strength in older adults. Such a strategy is still missing for older adults from ethnic minority populations. Protein intake in these populations is expected to be different in comparison to the majority of the population due to several socio-cultural factors. Therefore, the present study examined the dietary protein intake and underlying behavioral and environmental factors affecting protein intake among older adults from ethnic minorities in the Netherlands. We analyzed frequency questionnaire (FFQ) data from the Healthy Life in an Urban Setting (HELIUS) cohort using ANCOVA to describe dietary protein intake in older adults from ethnic minorities in the Netherlands (N = 1415, aged >55 years, African Surinamese, South Asian Surinamese, Moroccan, and Turkish). Additionally, we performed focus groups among older adults from the same ethnic minority populations (N = 69) to discover behavioral and environmental factors affecting protein intake; 40–60% of the subjects did not reach minimal dietary protein recommendations needed to maintain muscle mass (1.0 g/kg bodyweight per day (BW/day)), except for Turkish men (where it was 91%). The major sources of protein originated from animal products and were ethnic specific. Participants in the focus groups showed little knowledge and awareness about protein and its role in aging. The amount of dietary protein and irregular eating patterns seemed to be the major concern in these populations. Optimizing protein intake in these groups requires a culturally sensitive approach, which accounts for specific protein product types and sociocultural factors.

BackgroundThe recent finding that aortic pulse wave velocity (aPWV) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. Methods and ResultsA systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer‐reviewed publications on clinical studies reporting original data. This study followed the Preferred Reporting Items for Systematic Review and Meta‐Analyses of individual participant data 2015 guidelines. Data were provided for 4 cohorts in 3 countries (151 participants with ulcerative colitis, 159 with Crohn's disease, and 227 control patients). Using aPWV, cohort‐specific z scores were calculated after loge‐transform and combined in meta‐analysis to form pooled effects using a random‐effects model. Compared with controls, aPWV was increased in patients with Crohn's disease (mean difference 0.78 z score; 95% confidence interval, 0.56–1.00 z score [P

Ali Ozer,1 Aysun Yilmazlar,2 Ersin Oztürk,1 Tuncay Yilmazlar1 1Department of General Surgery, 2Department of Anesthesiology and Reanimation, Faculty of Medicine, Uludag University, Görükle, Turkey Background: In a previous prospective randomized trial, we showed that local anesthetic infusion using a preperitoneal catheter is an effective postoperative analgesic method following colorectal resections. Over time, we have improved the technique of preperitoneal catheter analgesia. In this prospective cohort study, we report the results of 100 consecutive patients who underwent colorectal resections. Materials and methods: Preperitoneal catheter analgesia was performed via a multihole catheter placed in the preperitoneal space using 10 mL 0.5% levobupivacaine every 4 hours following the operation for the first 3 days. Additional analgesics were used whenever necessary. Postoperative pain was assessed with the visual analog scale score. Short-term clinical outcomes, such as need for systemic analgesics, time to first gas and stool discharge, length of hospital stay, and morbidity, particularly surgical site infections, were reported. Results: From May 2009 to May 2010, 100 consecutive patients were recruited in the study. A total of 83 patients were operated on for malignancy, and the tumor was located in the rectum in 52 patients and in the colon in 31 patients. The median pain score was 4 (0–6), 3 (0–9), 2 (0–8), 1 (0–8), 1 (0–6), 0 (0–6), and 0 (0–3) at postoperative hours 0, 1, 4, 12, 24, 48, and 72, respectively. Additional analgesics were required in 34 patients: 21 of them required only nonsteroidal anti-inflammatory drugs, and 13 patients needed opioids additionally. The median amounts of opioid analgesics and nonsteroidal anti-inflammatory drugs were 1.76±0.78 mg and 6.70±1.18 mg, respectively. However, almost all of the additional analgesics were given in the first 24 hours. Surgical site infections were detected in eight patients. Conclusion: Preperitoneal catheter analgesia is an effective analgesic method. When applied and used properly, it may even be used as the sole analgesic method in some patients. Keywords: preperitoneal, colorectal, analgesia

The incidence of delirium after cardiac surgery varies between 3-70%. (1) Systemic inflammation disorders and/or inadequate cerebral perfusion are held responsible for the pathophysiology of delirium (2). The primer aim of this study was to investigate the effects of goal-directed fluid therapy in perioperative period on the development of delirium in the early period in patients undergoing cardiopulmonary bypass. The second aim was to determine rScO2 changes in patients with delirium. The study was designed prospectively at single academic center. A total of 108 patients (mean age: 60.6±9.1 years) scheduled for elective coronary artery bypass grafting between March 2022 and November 2022 were enrolled. Patients were divided into two groups: Group Study (Group S, n=54); goal directed fluid therapy were applied. Patients were monitored through an esophageal doppler probe in addition to standard invasive monitoring. Group Control (Group C, n=54), hemodynamics were managed by standard invasive monitoring (arterial and central venous pressure). Absolute and % change values of the right and left regional cerebral oxygen saturation (rScO2) were recorded before induction (T0), after induction(T1), at 5th minutes(T2) and at 30th minutes (T3) in extracorporeal circulation and at the end of operation(T4). Hemodynamic data were also recorded simultaneously. Confusion assessment method in intensive care unit (CAM-ICU) was used to evaluate postoperative delirium in the time period that the patients stayed in the ICU and until discharge of the hospital. Two independent groups were compared statistically with appropriate parametric and non-parametric tests. Results: Postoperative delirium developed in 3 patients (5.6%) in the Group C and in 9 patients (16.7%) in the Group S (Table 1). Right and left regional cerebral oxygen saturation (rScO2) and percentage changes over time were similar (Group S vs Group C; left frontal p=0.214, right frontal p=0.413, respectively). The percentage change in left frontal rScO2 in patients with delirium was lower than patients with non-delirium during extracorporal circulation (T2 and T3), (18.32±15.3, -14.8±11.3, p<0.001; -11.2±11.9, -13.8±9.9, p<0.001, respectively). Perioperative fluid requirements and blood and blood product requirements were not different from those in the control group. In our study, perioperative goal directed fluid therapy did not change the rates of postoperative delirium in patients undergoing coronary artery bypass surgery in early period. Delirium was detected in 9 patients (16.7%) in the study group and 3 (5.6%) patients in the control group. The goal directed therapy group had significantly more negative pump balance than the standard approach. Percentages of change in right and left regional cerebral oxygen saturation (rScO2) were significantly lower during extracorporeal circulation (at T2 and T3) compared to baseline values in both groups. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). Methods: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m 2 docetaxel and 20 mg/m 2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 were administered at each 21 days. Results: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. Conclusion: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.

Brown tumors of bone are highly vascular, lytic bone lesions representing a reparative cellular process rather than a neoplastic process usually seen in patients with hyperparathyroidism. These tumors can behave aggressively and be destructive. We report a 49-year-old male patient who was admitted to our hospital with a long-term history of right shoulder and right hip pain. Multiple lytic and destructive bone lesions were found in X-ray graphy and CT images. These bone lesions mimicked multiple skeletal metastatic lesions and seemed to be those of the terminal stage of malignancy. PET scan was requested for the evaluation of FDG uptake of these lesions and to search the unknown primary tumor site. Positron emission tomography/computed tomography (PET/CT) images showed multiple hypermetabolic malignant or metastatic FDG avid bone lesions in skeletal system. However the biopsy results revealed no signs of malignancy and laboratory data showed elevated serum calcium, alkaline phosphatase, parathyroid hormone, low serum phosphate and parathyroid scintigraphy was performed. Adenoma in the left parathyroid gland was seen with Tc-99m MIBI parathyroid scintigraphy. Pathological results confirmed the diagnosis of parathyroid adenoma. Brown tumor is the potential cause of false-positive result in evaluation of a patient for unknown primary tumor or skeletal metastases with PET/CT imaging.