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Nesfatin-1 is an anorexigenic peptide suppressing food intake and is synthesized and secreted by neurons located in the hypothalamus. Our study was aimed to demonstrate the effect of excitatory and inhibitory neurotransmitters on NUCB2/nesfatin-1 neurons. In this context, dual peroxidase immunohistochemistry staining was performed using NUCB2/nesfatin-1 primary antibody with each of the primary antibodies of vesicular transporter proteins applied as markers for neurons using glutamate, acetylcholine, and GABA as neurotransmitters. In double labeling applied on floating sections, the NUCB2/nesfatin-1 reaction was determined in brown color with diaminobenzidine, while vesicular carrier proteins were marked in black. Slides were analyzed to determine the ratio of nesfatin-1 neurons in the three hypothalamic nucleus in contact with a relevant vesicular carrier protein. The ratios of NUCB2/nesfatin-1 neurons with the innervation were compared among neurotransmitters. In addition, possible gender differences between males and females were examined. The difference in the number of VGLUT2-contacting NUCB2/nesfatin-1 neurons was significantly higher in males when compared to females. When both genders were compared in different nuclei, it was seen that there was no statistical significance in terms of the percentage of NUCB2/nesfatin-1 neuron apposition with VGLUT3. The statistical evaluation showed that number of NUCB2/nesfatin-1 neurons receiving GABAergic innervation is higher in males when compared to females (*p ≤ 0.05; p = 0.045). When the axonal contact of vesicular neurotransmitter transporter proteins was compared between the neurotransmitters, it was determined that the most prominent innervation is GABAergic. In the supraoptic region, no contacts of VAChT-containing axons were found on NUCB2/nesfatin-1 neurons in both female and male subjects. In conclusion, it is understood that both excitatory and inhibitory neurons can innervate the NUCB2/nesfatin-1 neurons and the glutamatergic system is effective in the excitatory innervation while the GABAergic system plays a role in the inhibitory mechanism., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.

Alzheimer's disease (AD) is a multifactorial pathology marked by amyloid beta (Aβ) accumulation, tau hyperphosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aβ levels and histological signs of neurotoxicity were detected using the enzyme-linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aβ accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD., Competing Interests: Declaration of Competing Interest The authors have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Medical trainees in obstetrics must develop competency in fetal ultrasonography. To date, no studies have utilized ultrasound simulator training for basic fetal anatomy with paired didactic coursework. We hypothesize that ultrasound simulator training with paired didactics improves medical trainee competency in fetal ultrasonography., Methods: A prospective observational study was performed at a tertiary care center during the 2021-2022 academic year. Medical trainees in obstetrics without prior simulator experience could participate. Participants completed ultrasound simulator training with standardized paired didactics and subsequent real-time patient scanning. All images were reviewed by the same physician for competency. Trainees completed 11-point Likert scale surveys at three time points: pre-simulator, post-simulator, and post-real-time patient scanning. Two-tailed student's t-tests with 95% confidence intervals were performed, and p-values <0.05 were considered significant., Results: Of the 26 trainees that completed the training, 96% reported that simulation positively impacted their confidence and ability to perform real-time scanning of patients. Self-reported knowledge of fetal anatomy, ultrasound techniques, and application to clinical obstetrics all significantly increased after simulator training (p < 0.01)., Conclusions: Paired ultrasound simulation with didactic instruction significantly improves medical trainees' knowledge of fetal anatomy and ability to perform fetal ultrasonography. Implementing an ultrasound simulation curriculum may become an essential tool for obstetric residency programs., (© 2023 Wiley Periodicals LLC.)

Introduction: Inguinal hernia repair is a common surgery, especially in the elderly population. However, the decision to perform surgery in elderly patients can be challenging due to higher complication rates. Laparoscopic inguinal hernia surgery is less commonly used in the elderly population despite its advantages. In this study, we aimed to investigate the safety and advantages of laparoscopic inguinal hernia surgery in elderly patients. Methods: We retrospectively compared the preoperative and postoperative (PO) data and Short Form-36 (SF-36) forms of elderly patients who underwent laparoscopic transabdominal preperitoneal and open inguinal hernia surgery. The primary outcomes were PO pain scores and complication rates. Results: A total of 79 patients with an age range between 65 and 86 years, who presented with inguinal hernias to Cekirge State Hospital's General Surgery Department between January 2017 and November 2019, were included. Seventy-nine patients underwent laparoscopic transabdominal preperitoneal technique and Lichtenstein hernia repair. The laparoscopic group had a lower rate of PO complications and less analgesic medication consumption and usage time compared with the open group. Furthermore, compared with the open group, the laparoscopic group had lower PO pain scores and higher SF-36 scores for physical function, physical role, pain, and general health at the 30th and 90th days after surgery. Conclusion: Our study suggests that laparoscopic inguinal hernia surgery can be safely performed in elderly patients with lower complication rates and faster recovery times compared with open surgery. The advantages of laparoscopic surgery, such as lower PO pain scores and faster recovery times, were also observed in elderly patients.

Due to its antioxidant and antimicrobial properties, sulfur dioxide (SO 2 ) is widely used in foods and beverages to prevent the growth of microorganisms and to preserve the color and flavor of fruits. However, the amount of SO 2 used in fruit preservation should be limited due to its possible adverse effects on human health. The present study was designed to investigate the effects of different SO 2 concentrations in apricot diets on rat testes. Animals were randomly divided into six groups. The control group was fed a standard diet, and the other groups were fed apricot diet pellets prepared with (w/w) 10% dried apricots containing SO 2 at different concentrations (1500 ppm, 2000 ppm, 2500 ppm, 3000 ppm, and 3500 ppm/kg) for 24 weeks. After sacrification, testicles were evaluated biochemically, histopathologically, and immunohistopathologically. Our results showed that an apricot diet containing 1500 ppm and 2000 ppm SO 2 did not cause significant changes in testis. However, it was determined that tissue testosterone levels decreased as the amount of SO 2 (2500 ppm and above) increased. Apricot diet containing 3500 ppm SO 2 caused a significant increase in spermatogenic cell apoptosis, oxidative damage, and histopathological changes. In addition, a decrease in the expression of connexin-43, vimentin, and 3β-hydroxysteroid dehydrogenase (3β-HSD) was observed in the same group. In summary, the results show that sulfurization of apricot at high concentrations such as 3500 ppm may lead to male fertility problems in the long term through mechanisms such as oxidative stress, spermatogenic cell apoptosis, and inhibition of steroidogenesis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods., Methods: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values., Results: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group ( p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR&#95;005492522.1, rna-XR&#95;005492536.1, and rna-XR&#95;005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity., Conclusions: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

Objectives: Cyclophosphamide is a chemotherapeutic agent and immunosuppressant drug; however, it damages the liver. This study investigates the protective effect of ethanolic extract of Allium scorodoprasum (ASE) on cyclophosphamide-induced liver injury., Methods: Twenty-eight Wistar albino rats were randomly divided into four groups (n = 7 per group): healthy rats, cyclophosphamide (200 mg/kg), cyclophosphamide (200 mg/kg) + ASE (100 mg/kg) and cyclophosphamide (200 mg/kg) + ASE (200 mg/kg). ASE was administered for 14 days, and the rats were euthanized 24 h after cyclophosphamide administration., Key Findings: Cyclophosphamide treatment leads to an increase in serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein, as well as an increase in the liver levels of malondialdehyde, tumour necrosis factor, interleukin (IL)-1β and IL-6, while high-density lipoprotein levels decrease. Treatment with cyclophosphamide caused liver necrosis and postnecrotic cell infiltration; however, pathological changes were prevented by ASE. 8-Hydroxy-2'-deoxyguanosine, anti-4-hydroxynenal antibody and anti-dityrosine levels increased in rats treated with cyclophosphamide and decreased in the groups treated with ASE. These changes were dose dependent in the ASE-treated groups., Conclusions: Treatment with cyclophosphamide caused liver damage due to oxidative stress and inflammation. ASE regulated the damage at high doses because it has potent antioxidant and anti-inflammatory ingredients. In future studies, it may be beneficial to administer ASE in higher doses or for longer periods of time., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Mesenteric circulation is provided by the celiac trunk (CT), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA). The collateral circulation between CT and SMA and between SMA and IMA plays a protective role against intestinal ischemia in case of narrowing or occlusion of the mesenteric vessels. In our study, it is aimed to determine the CT and SMA stenosis rates in patients with CT and SMA stenosis from angiography images, the occurrence of the collateral variations, and the frequency of these variations., Methods: A total of 408 non-selective or selective CT and SMA angiographic images were taken of 215 patients (130 males, 85 females) who were admitted to Akdeniz University Hospital with symptoms of chronic mesenteric ischemia (CMI) were included. The angiography images were analyzed in regards to CT and SMA stenosis rates, and the collateral variations between mesenteric vessels., Results: Stenosis of CT was observed in 14 patients, whereas the stenosis of the SMA was observed in 12 patients. The most common collateral vessel in these patients was the gastroduodenal artery. Both stenoses of CT and SMA were found in 9 patients. The Riolan arch was the most common type of collateral vessel in these patients., Conclusion: It was observed that mesenteric circulation was mainly provided by gastroduodenal artery in patients with isolated CT or SMA stenosis or occlusion while in patients with stenosis or occlusion of both CT and SMA, mesenteric circulation was mainly provided by the Riolan arch. A significant increase was observed in the prominence of collateral vessels in patients with stenosis of more than 70%., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Background: Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer., Objectives: The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats., Material and Methods: The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken., Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1β, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group., Conclusions: According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.

Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups - (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1β and TGF-β3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: To assess outcomes in twin-twin transfusion syndrome (TTTS) according to middle cerebral artery pulsatility index (MCA-PI) prior to fetoscopic laser photocoagulation (FLPC) surgery., Methods: A retrospective cohort analysis of monochorionic-twin pregnancies complicated by TTTS who underwent FLPC at two fetal centers (2012-2021). The cohort was stratified according to abnormal MCA-PI of the donor twin, defined as below fifth centile for gestational age., Results: Abnormal MCA-PI of the donor twin was detected in 46 (17.7%) cases compared to 213 (83.3%) controls with no such abnormality. The abnormal PI group presented with higher rates of sFGR (56.5% vs. 36.8% in controls, p = 0.014) and lower donor survival rates within 48 h after FLPC (73.9 vs. 86.8%, p = 0.029). Donor twin survival rates at the time of delivery and 30 days after birth were lower in the abnormal MCA-PI. Multivariate logistic regression analysis controlling for sFGR and MCA-PI

Background: Relapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma., Methods: All patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m 2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter., Results: Between January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively., Conclusion: Our study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma., 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 Olgun, Cecen, Ince, Kizmazoglu, Baysal, Onal, Ozdogan, Guleryuz, Cetingoz, Demiral, Olguner, Celik, Kamer, Ozer, Altun and Aktas.)

Background: To translate and validate the psychometric characteristics of a Turkish version of the Obstetric Quality-of-Recovery score 11 tool used to measure post-cesarean delivery recovery in Turkish-speaking patients., Methods: After the original English version of the Obstetric Quality-of-Recovery score 11 tool was translated into Turkish; it was psychometrically validated to assess the post-cesarean delivery quality of recovery. Validity, reliability, and feasibility were investigated. The Obstetric Quality-of-Recovery score 11 tool was administered to Turkish-speaking patients on postoperative day 1. On postoperative day 1, a global health visual analog scale was used to assess the patient's perceived global recovery., Results: One hundred and eighty-six patients completed their questionnaires, providing a completion rate of 97.38%. The Spearman rho (ρ) correlation coefficient between the Obstetric Quality-of-Recovery score and global health visual analog scale (0-100 points) was 0.850 at postoperative day 1 following surgery (P < 0.001). Internal consistency, measured using Cronbach's alpha, was 0.822. The split-half coefficient was 0.708. The Obstetric Quality-of-Recovery score differed significantly between the emergency and elective cesarean delivery groups (80 (41-104) vs. 83.3 (51-102); P < 0.05). The test-retest reliability of the Obstetric Quality-of-Recovery score items was more than 0.6 in 82% of cases, indicating good repeatability and reliability., Conclusion: The Obstetric Quality-of-Recovery score 11 is a valid and reliable tool to measure the post-cesarean quality of recovery in Turkish-speaking patients. The psychometric properties of the Turkish version of the scale to measure the post-cesarean quality of recovery were similar to those of the seminal English version., (© 2022. The Author(s).)

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operator-induced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L-929 cells), biodegradable, and antibacterial (on Escherichia coli , Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing.

Aim: This study aimed to evaluate the usefulness and accuracy of the delta neutrophil index (DNI), an index expressing the number of immature granulocytes as a proportion of the total, as an inflammatory marker in predicting serious bacterial infections (SBIs)., Methods: Paediatric patients admitted to our hospital with fever were divided into four groups: SBI, non-SBI, COVID-19 and control group. White blood cell count, absolute neutrophil count, C-reactive protein and the DNI were recorded, and their accuracy in predicting SBI was evaluated., Results: Mean DNI was 4.96 ± 8.38 in the SBI group (150 patients), 0.67 ± 1.68 in the non-SBI group (397 patients), 0.29 ± 0.99 in the COVID-19 group (112 patients) and 0.14 ± 0.21 in the control group (102 patients). The DNI was significantly higher in the SBI group compared with the non-SBI (P < 0.001); the non-SBI group also had higher levels than the COVID-19 group (P = 0.005). One percent increase in the DNI increased the SBI rate 1.36 times (odds ratio 1.36 (95% confidence interval 1.23-1.49), P < 0.001). Based on the determined cut-off value (>2.5%), the DNI (odds ratio 6.27 (95% confidence interval 3.85-10.21), P < 0.001) significantly predicted SBIs with 90.4% specificity and 47.7% sensitivity., Conclusions: SBIs in childrenare associated with an increase in DNI levels. Compared to other biomarkers, the DNI had higher specificity in predicting SBIs. The DNI may also be usefulin differentiating bacterial and non-bacterial infections in individualclinical syndromes. Currently, there is no evidence that serum DNI aids indifferentiating COVID-19 and upper respiratory tract infection., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats., Methods: The animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion+uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion+uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes., Results: In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups., Conclusion: Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.

COVID-19 has been in the headlines for the past two years. Diagnosing this infection with minimal false rates is still an issue even with the advent of multiple rapid antigen tests. Enormous data are being collected every day that could provide insight into reducing the false diagnosis. Machine learning (ML) and deep learning (DL) could be the way forward to process these data and reduce the false diagnosis rates. In this study, ML and DL approaches have been applied to the data set collected using an ultra-fast COVID-19 diagnostic sensor (UFC-19). The ability of ML and DL to specifically detect SARS-CoV-2 signals against SARS-CoV, MERS-CoV, Human CoV, and Influenza was investigated. UFC-19 is an electrochemical sensor that was used to test these virus samples and the obtained current response dataset was used to diagnose SARS-CoV-2 using different algorithms. Our results indicate that the convolution neural networks algorithm could diagnose SARS-CoV-2 samples with a sensitivity of 96.15%, specificity of 98.17%, and accuracy of 97.20%. Combining this DL model with the existing UFC-19 could selectively identify SARS-CoV-2 presence within two minutes.

The severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) has spread globally and there is still a lack of rapid detection techniques for SARS-CoV-2 surveillance in indoor air. In this work, two test rigs were developed that enable continuous air monitoring for the detection of SARS-CoV-2 by sample collection and testing. The collected samples from simulated SARS-CoV-2 contaminated air were analyzed using an ultra-fast COVID-19 diagnostic sensor (UFC-19). The test rigs utilized two air sampling methods: cyclone-based collection and internal impaction. The former achieved a limit of detection (LoD) of 0.004 cp/L in the air (which translates to 0.5 cp/mL when tested in aqueous solution), lower than the latter with a limit of 0.029 cp/L in the air. The LoD of 0.5 cp/mL using the UFC-19 sensor in aqueous solution is significantly lower than the best-in-class assays (100 cp/mL) and FDA EUA RT-PCR test (6250 cp/mL). In addition, the developed test rig provides an ultra-fast method to detect airborne SARS-CoV-2. The required time to test 250 L air is less than 5 min. While most of the time is consumed by the air collection process, the sensing is completed in less than 2 s using the UFC-19 sensor. This method is much faster than both the rapid antigen (<20 min) and RT-PCR test (<90 min).

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups ( p  > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group ( p  > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups ( p  > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Valproate (VPA) induced changes in ovarian morphology are observed in humans with epilepsy and in non-epileptic animals. The effects of lamotrigine (LTG) on female reproduction is not well known. We investigated whether LTG might be a safer drug for use with patients of reproductive age. Forty Wistar albino female rats were divided into five groups. The control group was injected with saline-vehicle solution. The low dose (LD)-VPA group was injected with 100 mg/kg VPA. The high dose (HD)-VPA group was injected with 500 mg/kg VPA. The LD-LTG group was injected with 10 mg/kg LTG. The HD-LTG group was injected with 50 mg/kg LTG. We evaluated histological and biochemical changes in the ovaries. The number of atretic and cystic follicles was increased in the HD-VPA and HD-LTG groups compared to the control group. A significant increase in malondialdehyde level was found in the VPA groups compared to the control and LTG groups. No significant differences in total glutathione levels or superoxide dismutase activity were found among study groups. Catalase activity was significantly higher in HD-VPA and HD-LTG groups compared to the control, LD-VPA and LD-LTG groups. Prevalence and intensity of caspase-3 immunoreactivity in the luteal cells were significantly greater in the HD-LTG group compared to the control group. VPA administration caused polycystic ovarian syndrome-like changes in the ovary. We found that LD-LTG, which reflects the dose for humans, might be a safer option for use during the reproductive age.

We performed a systematic study involving simulation and experimental techniques to develop induced-junction silicon photodetectors passivated with thermally grown SiO 2 and plasma-enhanced chemical vapor deposited (PECVD) SiN x thin films that show a record high quantum efficiency. We investigated PECVD SiN x passivation and optimized the film deposition conditions to minimize the recombination losses at the silicon-dielectric interface as well as optical losses. Depositions with varied process parameters were carried out on test samples, followed by measurements of minority carrier lifetime, fixed charge density, and optical absorbance and reflectance. Subsequently, the surface recombination velocity, which is the limiting factor for internal quantum deficiency (IQD), was obtained for different film depositions via 2D simulations where the measured effective lifetime, fixed charge density, and substrate parameters were used as input. The quantum deficiency of induced-junction photodiodes that would be fabricated with a surface passivation of given characteristics was then estimated using improved 3D simulation models. A batch of induced-junction photodiodes was fabricated based on the passivation optimizations performed on test samples and predictions of simulations. Photodiodes passivated with PECVD SiN x film as well as with a stack of thermally grown SiO 2 and PECVD SiN x films were fabricated. The photodiodes were assembled as light-trap detector with 7-reflections and their efficiency was tested with respect to a reference Predictable Quantum Efficient Detector (PQED) of known external quantum deficiency. The preliminary measurement results show that PQEDs based on our improved photodiodes passivated with stack of SiO 2 /SiN x have negligible quantum deficiencies with IQDs down to 1 ppm within 30 ppm measurement uncertainty.

Objective: Evaluate survival in twin twin transfusion syndrome (TTTS) with and without selective fetal growth restriction (sFGR) after fetoscopic laser surgery (FLS)., Methods: Retrospective study of monochorionic diamniotic twins undergoing FLS. The cohort was classified as TTTS and TTTS with sFGR. Baseline, intra-operative and postoperative variables were analyzed. Mann-Whitney U, Pearson chi-square, Fisher's exact, t-test and receiver operating characteristic (ROC) curve analysis were performed., Results: Four hundred and ninety-two pregnancies were included, 304 (61.78%) TTTS and 188 (38.22%) TTTS with sFGR. No difference in donor outcomes. TTTS group had higher donor estimated fetal weight (EFW%) percentile (19.7 ± 18.8 vs. 2.2 ± 2.1, p < 0.001). Significant predictors for demise at 30 days were 37% intertwin weight discordance (IWD) with donor EFW% < first (area under ROC curve [AUC] = 0.85, p = 0.001) or IWD >25% and intertwin umbilical artery pulsatility index discordance (DUAPI) ≥0.4 (AUC = 0.71, p = 0.001)., Conclusion: Combination of IWD of 37% and donor EFW%

Purpose: The aim was to evaluate the effectiveness of bacterial cellulose membrane (BCM) in preventing fibrosis in trabeculectomy and the biocompatibility of BCM with conjunctiva and sclera., Materials and Methods: Twenty-one eyes of 21 adult rabbits underwent fornix-based trabeculectomy. Standard surgery was done to control group (CG, n=7). Mitomycin-C (MMC) (0.3 mg/mL, 3 min) was applied to MMC group only (MMCG, n=7). BCM (~100 µm thick, 10×10 mm, single layer) was covered on the sclerotomy area before conjunctiva was closed in BCM group (BCMG, n=7). Intraocular pressures (IOP) were measured before, and 7, 14, 28, and 45 days after surgery (IOP-POD7, POD14, POD28, POD45). The IOP decrease were expressed as DIOP%-POD7, DIOP%-POD14, DIOP%-POD28, and DIOP%-POD45. The rabbits were sacrificed on the 45th day. Conjunctival vessel number, degrees of fibrosis, total inflammation, foreign body reaction, inflammatory cell types (B cells, T cells, plasma cells), macrophages, bleb spaces and the expression of α-smooth muscle actin were studied using histopathology and immunohistochemistry techniques. The groups were compared using nonparametric tests., Results: There was no statistically significant difference between the groups regarding baseline IOP and DIOP%-POD7 (P>0.05). While DIOP%-POD14, 28 and 45 were similar between BCMG and MMCG, they were significantly lower in CG (P<0.05). The lowest conjunctival vessel number was detected in the MMCG but the difference was not significant. There was no difference between BCMG and CG with regard to the numbers of B cells, T cells, and macrophages, however, these cells were significantly lower in MMCG (P<0.05). Five cases had mild and 2 cases had moderate foreign body reaction in the BCMG. There was mild to moderate inflammation in all BCM cases. While fibrosis and α-smooth muscle actin staining were higher in the CG (P<0.001), they were minimal in the BCM and MMCGs., Conclusions: BCM showed good biocompatibility and provided better control of IOP with minimal fibrosis at the trabeculectomy site compared with the control group., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: There are very few studies in the literature investigating the changes caused by the Nathanson retractors in liver function tests (LFT) after LG and its clinical significance. The present study investigated the changes made by the Nathanson retractor used during LG on LFT and its clinical significance., Material and Method: The data of 236 patients, who underwent radical gastrectomy for primary gastric cancer at Surgical Oncology Unit in the period between January 2015 and January 2020 were retrospective studied. The patients were divided into two groups: laparoscopic gastrectomy (LG; 136 cases) and open gastrectomy (OG; 106 cases). Patients who have undergone cholecystectomy, with primary or secondary liver tumors, with chronic hepatic disease, who have preoperative high ALT, AST and bilirubin values were excluded from the study. LFT were measured preoperatively and postoperative day 1 (LFT1), LFT3, LFT5 and LFT7. LFT: ALT, AST and Total bilirubin (BIL)., Results: ALT1, ALT3, ALT5, ALT7 ALT values and AST1, AST3, AST5 AST values of the patients in the LG group were found to be significantly higher (P &lt;0.001). Mean total bilirubin values of the groups were similar (P &gt;0.05). In order to evaluate how the increase in LFT due to the use of the Nathanson retractors reflected on the patients&apos; clinic, we divided the patients who underwent LG into two groups based on ALT increase in ALT1: Normal and Elevated. The in-hospital mortality rates (P = 0.080) and oral nutrition time (P = 0.913) of the groups were similar. No liver infarction developed in any of the groups. The duration of stay in the ICU was significantly longer in individuals with elevated LFT (P = 0.019)., Conclusion: Although the use of the Nathanson retractor during LG causes an increase in liver function tests, this does not cause major clinical problems in patients. Key Words: Gastrectomy; gastric cancer; laparoscopy; liver enzymes; liver dysfunciton.

Benomyl, benzimidazole group pesticide, has been prohibited in Europe and USA since 2003 due to its toxic effects and it has been still determined as food and environmental contaminant. In the present study, the toxic effect mechanisms of benomyl were evaluated in rat cardiomyoblast (H9c2) cells. Cytotoxicity was determined by MTT and NRU assay and, oxidative stress potential was evaluated by reactive oxygen species (ROS) production and glutathione levels. DNA damage was assessed by alkaline comet assay. Relative expressions of apoptosis related genes were evaluated; furthermore, NF-κB and JNK protein levels were determined. At 4 μM concentration (at which cell viability was >70%), benomyl increased 2-fold of ROS production level and 2-fold of apoptosis as well as DNA damage. Benomyl down-regulated miR21, TNF-α and Akt1 ≥ 48.75 and ≥ 97.90; respectively. PTEN, JNK and NF-κB expressions were upregulated. The dramatic changes in JNK and NF-κB expression levels were not observed in protein levels. These findings showed the oxidative stress related DNA damage and apoptosis in cardiomyoblast cells exposed to benomyl. However, further mechanistic and in vivo studies are needed to understand the cardiotoxic effects of benomyl and benzimidazol fungucides., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The application of plant growth-promoting rhizobacteria (PGPRs) can be an excellent and eco-friendly alternative to the use of chemical fertilizers. While PGPRs are often used in traditional agriculture to facilitate yield increases, their use in soilless agriculture has been limited. Soilless agriculture is growing in popularity among commercial farmers because it eliminates soil-borne problems, and the essential strategy is to keep the system as clean as possible. However, a new trend is the inclusion of PGPRs to enhance plant development. Despite the plethora of research that has been performed to date, there remains a huge knowledge gap that needs to be addressed to facilitate the commercialization of PGPRs for sustainable soilless agriculture. Hence, the development of proper strategies and additional research and trials are required. The present review provides an update on recent developments in the use of PGPRs in soilless agriculture, examining these bacteria from different perspectives in an attempt to generate critical discussion and aid in the understanding of the interaction between soilless agriculture and PGPRs., Competing Interests: Conflict of interestsNo potential conflict of interest was reported by the authors., (© King Abdulaziz City for Science and Technology 2021.)

Myocardial ischemia may occur as a result of pathophysiological and therapeutical applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery bypass, and transplantation. In this study, we aimed to compare the effects of angiotensin (Ang) II type 2 (AT 2 ) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT 1 ) selective receptor blocker losartan, and Ang-converting enzyme inhibitor captopril on haemodynamic parameters and infarct size on myocardial ischemia/reperfusion (MI/R)-induced necrosis in rats. To induce necrosis in the heart of rats, reperfusion for 2 h following ischemia for 30 min to the descending branch of the left main coronary artery was achieved. C21 (0.03 mg/kg), AVE 0991 (576 μg/kg), losartan (2 mg/kg), and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. Then, the infarct size and risk area were calculated from the heart. The percentage of myocardial infarct size to area at risk ratio (%IS/AR) of groups was Control (MI/R) group: 48.9 ± 8.8%; C21 group: 31.1 ± 7.8%; AVE 0991 group: 29.9 ± 4.8%; C21 + AVE 0991 group: 28.2 ± 3.3%; Losartan + AVE 0991 group: 30.8 ± 5.8%; Captopril + AVE 0991 group: 31.7 ± 7.7%. %IS/AR of the drug-treated groups decreased significantly when compared to the MI/R group (P < 0.05). Our results indicate that the importance of AT 1 , AT 2 , and MAS receptors in the MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT 1 receptor with losartan, and stimulation of AT 2 receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing infarct size., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Objectives: High anxiety levels may lead to mental and physical changes that may affect quality of life. Melatonin has anxiolytic properties. It has been reported that administration of melatonin reduces anxiety. In this study, we examined the preoperative and postoperative anxiety levels of living liver donors and the correlation between anxiety levels and endogenous melatonin levels., Materials and Methods: This prospective clinical study included 56 living liver donors who underwent right hepatectomy (39 women, 17 men; average age of 29 ± 7 years). The anxiety levels were evaluated by using the Spielberger State-Trait Anxiety Inventory Test with a form for this test used to measure the current state of anxiety score and another form used to measure the underlying anxiety score of the patient. These forms were applied preoperatively and postoperatively. Blood samples were taken simultaneously for melatonin levels. Melatonin levels were measured using high-pressure liquid chromatography. Our primary outcomes were to determine the preoperative and postoperative endogenous melatonin and anxiety levels of living liver donors and to investigate their correlations., Results: A statistically significant difference was observed between preoperative and postoperative state of anxiety scores. The preoperative and postoperative underlying anxiety scores were similar. A statistically significant difference was found between the preoperative endogenous melatonin level and postoperative endogenous melatonin level. A significant correlation was not observed between the preoperative and postoperative current and underlying anxiety levels or endogenous melatonin levels., Conclusions: Living liver donors had high anxiety levels during the preoperative and postoperative periods. A significant decrease was identified in the postoperative hour 24 endogenous melatonin level. These results may lay the foundation for interventions that can identify emotional changes as well as control and improve the mental health of living liver donors.

Background: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations., Objective: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection., Study Design: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data., Results: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes., Conclusion: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To evaluate the association of intertwin differences in umbilical artery pulsatility index (DUAPI) and infant survival in twin-to-twin transfusion syndrome (TTTS)., Methods: Absolute DUAPI was calculated prior to laser surgery. Receiver-operating characteristics (ROC) curve analysis provided an intertwin DUAPI cutoff of 0.4 for the prediction of double twin survival to 30 days of life. Infant survival was compared between women with an intertwin DUAPI <0.4 and ≥0.4 in the whole cohort, in TTTS cases with Quintero stages I/II and in those with Quintero stages III/IV. Regression analyses were performed to evaluate the association of intertwin DUAPI <0.4 and infant survival adjusted for confounders., Results: In total, 349 TTTS cases were included. Double twin survival to 30 days was observed in 67% (234/349) of cases. Significant differences in double twin survival was seen between intertwin DUAPI groups in the whole cohort (76.8 vs. 52.2%; p<0.001), in women with TTTS Quintero stage I or II (77.8 vs. 58.5%; p=0.015) as well as in women with TTTS Quintero stage III or IV (75 vs. 49.5%; p=0.001). Intertwin DUAPI <0.4 conferred a threefold increased chance for double twin survival., Conclusions: Small intertwin DUAPI is associated with increased double infant survival in early and advanced TTTS stages., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Machine learning and deep learning frameworks have been presented as a substitute for lengthy computational analysis, such as finite element analysis, computational fluid dynamics, and fluid-structure interaction. In this study, our objective was to apply a deep learning framework to predict the geometric orifice (GOA) and the coaptation areas (CA) of the polymeric heart valves under the time-varying transvalvular pressure. 377 different valve geometries were generated by changing the control coordinates of the attachment and the belly curve. The GOA and the CA values were obtained at the maximum and the minimum transvalvular pressure, respectively. The results showed that the applied framework can accurately predict the GOA and the CA despite being trained with a relatively smaller data set. The presented framework can reduce the required time of the lengthy FE frameworks., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Paragangliomas (PGLs) are rare tumors with an incidence of 0.007% in pregnant women. Patients with PGLs commonly present with hypertension and tachycardia. This case report describes the evaluation and management of a multiparous woman at 32 weeks of gestation with syncope, hypoxia, and tachycardia as unusual presenting symptoms of PGL. Her symptoms were attributable to paradoxical effects of circulating catecholamines on downregulated alpha-adrenergic receptors resulting in decreased systemic vascular resistance., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Transmediastinal gunshot wounds (TGWs) may lead to life-threatening injuries of vital organs such as large vessels, the esophagus, and lungs. Although they are not commonly encountered in pregnant women, additional caution should be given to these patients. Physical examination for the diagnosis and the choice of treatment modality contain controversial points in hemodynamically stable patients, and resuscitation has excessive importance due to physiological changes in pregnancy. We present a hemodynamically stable 26-week pregnant woman brought to the emergency department for TGW. She had a 1-cm diameter of bullet entrance hole on the right anterior 4 th intercostal space, 2 cm lateral to the sternum, and a 3-cm diameter exit hole on the right posterior 12 th intercostal space on the midscapular line. With our conservative approach, she had an uncomplicated pregnancy period, and gave birth to a healthy baby at term., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Aim: To demonstrate the various technical advantages of minimally invasive endoscopic untethering of tight filum terminale for the treatment of tethered cord syndrome (TCS)., Material and Methods: In five pediatric cases of TCS, we performed untethering by using the endoscopic technique. The age of the patients were 6, 7, 8, 9, and 12 years old. We used a nasal speculum of the transsphenoidal approach during the endoscopic surgical procedure., Results: All the procedures were performed uneventfully, except for one case with a split cord malformation that showed neurologic deterioration caused by excision of the diastematomyelic fibrous septum at the thoracic level (unrelated to the endoscopic procedure at the L5-S1 level). This patient was referred to a rehabilitation clinic 5 days after surgery and showed significant improvement by the third postoperative month. The other four patients were discharged 1 day after the operation., Conclusion: Endoscopic release of filum terminale is a safe technique especially if it is performed with neuromonitoring. This technique may shorten the length of hospital stay and reduce perioperative blood loss. However, futher studies with a larger number of patients and long-term follow-up are needed.

This study investigated the protective effects of Compound 21 (C21), the first specific non-peptide AT2 receptor agonist, on cardiac injury in rats with isoproterenol-induced heart failure in vivo and compared it with valsartan, an AT1 receptor antagonist. In this study, 56 Wistar albino male rats (estimated body weights 250-400 g) were divided into eight groups (n = 7). Group 1 (Control) received no drug. Group 2 (ISO) was given 180 mg/kg of isoproterenol subcutaneously (s.c.); two doses were administered at 24-h intervals on days 29 and 30 of the experiment. Groups 3, 4, and 5 were given valsartan (30 mg/kg orally), C21 (0.03 mg/kg intraperitoneally), and a combination of Valsartan + C21, respectively, for 30 days. Groups 6, 7, and 8 were administered Valsartan, C21, and Valsartan + C21 in the same application, duration, and dose, respectively, and isoproterenol (180 mg/kg s.c.) was given on days 29 and 30 of the experiment. Transthoracic echocardiography was performed on the rats at the beginning and end of the experiment. Blood pressure, heart rate, and ECG alterations were monitored via a carotid artery cannula at the end of the experiment. Histopathological and biochemical measurements were performed on the cardiac tissue of the rats. For histopathological findings, C21 and Valsartan + C21 combination therapy significantly reduced the development of heart failure compared to valsartan alone. Also, the protective effect of C21 on myocardial injury was superior to that of valsartan. According to the results of echocardiographic and biochemical evaluations, C21, and Valsartan showed protective effects against heart failure. C21, valsartan, and combined therapy significantly prevented the decrease of ejection fraction. This report describes the cardioprotective effects of C21 and valsartan in ISO-induced myocardial damage.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

PDA is a major cause of US cancer-related deaths. Oncogenic Kras presents in 90% of human PDAs. Kras mutations occur early in pre-neoplastic lesions but are insufficient to cause PDA. Other contributing factors early in disease progression include chronic pancreatitis, alterations in epigenetic regulators, and tumor suppressor gene mutation. GPCRs activate heterotrimeric G-proteins that stimulate intracellular calcium and oncogenic Kras signaling, thereby promoting pancreatitis and progression to PDA. By contrast, Rgs proteins inhibit Gi/q-coupled GPCRs to negatively regulate PDA progression. Rgs16::GFP is expressed in response to caerulein-induced acinar cell dedifferentiation, early neoplasia, and throughout PDA progression. In genetically engineered mouse models of PDA, Rgs16::GFP is useful for pre-clinical rapid in vivo validation of novel chemotherapeutics targeting early lesions in patients following successful resection or at high risk for progressing to PDA. Cultured primary PDA cells express Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo. Here we establish the use of Rgs16::GFP expression for testing drug combinations in cell culture and validation of best candidates in our rapid in vivo screen.

Objective:  Primary dysmenorrhea occurs due to abnormal levels of prostanoids, uterine contractions, and uterine blood flow. However, the reasons for pain in primary dysmenorrhea have not yet been clarified. We examined the blood flow alterations in patients with primary dysmenorrhea and determined the relationship between ischemia-modified albumin (IMA) levels, as an ischemia indicator, and primary dysmenorrhea., Methods:  In the present study, 37 patients who had primary dysmenorrhea and were in their luteal and menstrual phase of their menstrual cycles were included. Thirty individuals who had similar demographic characteristics, who were between 18 and 30 years old and did not have gynecologic disease were included as control individuals. Their uterine artery Doppler indices and serum IMA levels were measured., Results:  Menstrual phase plasma IMA levels were significantly higher than luteal phase IMA levels, both in the patient and in the control groups ( p  < 0.001). Although the menstrual phase IMA levels of patients were significantly higher than those of controls, luteal phase IMA levels were not significantly different between the two groups. Menstrual uterine artery pulsatility index (PI) and resistance index (RI) of primary dysmenorrhea patients were significantly different when compared with luteal uterine artery PI and RI levels. There was a positive correlation between menstrual phase IMA and uterine artery PI and RI in the primary dysmenorrhea., Conclusion:  Ischemia plays an important role in the etiology of the pain, which is frequently observed in patients with primary dysmenorrhea. Ischemia-modified albumin levels are considered as an efficient marker to determine the severity of pain and to indicate ischemia in primary dysmenorrhea., Competing Interests: The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Nesfatin-1, identified as an anorexigenic peptide, regulates the energy metabolism by suppressing food intake. The majority of nesfatin-1-synthesizing neurons are concentrated in various hypothalamic nuclei, especially in the supraoptic (SON), arcuate (ARC) and paraventricular nuclei (PVN). We tested the hypothesis that the glutamatergic system regulates nesfatin-1 neurons through glutamate receptors. Therefore, the first aim of the proposed studies was to examine effects of different glutamate agonists in the activation of nesfatin-1 neurons using c-Fos double immunohistochemical labeling. Experimental groups were formed containing male and female rats which received intraperitoneal injections of glutamate agonists kainic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) while the control rats received vehicle. The significant increase in the number of c-Fos-expressing nesfatin-1 neurons after agonist injections were observed both in female and male subjects and some of these effects were found to be sexually dimorphic. In addition, treatment with specific glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or dizocilpine (MK-801) before each of the three agonist injections caused a statistically significant reduction in the number of activated nesfatin-1 neurons in the hypothalamic nuclei including supraoptic, paraventricular and arcuate nuclei. The second aim of the study was to determine the expression of glutamate receptor subunit proteins in the nesfatin-1 neurons by using a double immunofluorescence technique. The results showed that the glutamate receptor subunits, which may form homomeric or heteromeric functional receptor channels, were expressed in the nesfatin-1 neurons. In conclusion, the results of this study suggest that nesfatin-1 neurons respond to glutamatergic signals in the form of neuronal activation and that the glutamate receptors that are synthesized by nesfatin-1 neurons may participate in the glutamatergic regulation of these neurons.

Cecal ligation and puncture (CLP) is a commonly used model of sepsis in vivo. We investigated the effects of dexpanthenol (DXP) on heart, lung and aorta in CLP-induced sepsis in rats. Rats were divided into four groups of eight: group 1, sham (SH); group 2 (DXP), 500 mg/kg DXP injected intraperitoneally (i.p.); group 3 (CLP), CLP performed; group 4 (CLP + DXP), 500 mg/kg DXP injected i.p. after CLP. Heart, lung and aorta specimens were harvested for histopathological and biochemical analysis. Heart rate increased in group 3 compared to group 1; DXP administration to group 4 did not alleviate this change. In heart tissue samples, MDA levels were decreased significantly in groups 2 and 4 compared to group 3. The levels of GSH in groups 2 and 3 were elevated compared to groups 1 and 2. SOD activity was increased significantly in group 4 compared to group 3. CAT activity for group 4 was increased significantly compared to groups 1 and 3. We found that caspase-9 and caspase-3 activity was increased after application of CLP. Also, DXP treatment decreased the number of caspase-positive cells significantly compared to group 3. DXP appears to be promising for reducing sepsis-related mortality.

Large palatal fistulas after cleft palate surgery are difficult to treat using local mucoperiosteal flaps alone, particularly if multiple attempts to close the fistulas have resulted in tissue scarring. In this study, we present our 15-year surgical experience with tongue flaps for large palatal fistulas. A total of 34 patients who underwent tongue flap surgery at our institution between January 2000 and January 2015 were retrospectively analyzed. An anteriorly-based dorsal tongue flap was used for the treatment of anteriorly localized large palatal fistulas in all patients. Data including demographic characteristics of the patients, previous surgeries, localization of the fistula, time between the first and second surgery, and complications were recorded. Factors affecting the surgical success were evaluated. Of the patients, 21 were males and 13 were females with a mean age of 11.7 ± 6.9 (range: 4 to 29) years. Detachment of the tongue flap was observed in nine patients after surgery. Seven of the patients with detachment were male aged ≤6 years ( p  < 0.05). Resuturing the flap back to the defect did not significantly affect the results. Our study results suggest that proper patient selection and attentive and rigorous surgical technique have a critical importance in the tongue flap repair and tongue flap is not recommended for patients who are under seven years of age.

Objective: This study aimed to identify the optimal gestational age for delivery of pregnancies complicated by fetal growth restriction (FGR) without Doppler abnormalities., Study Design: Cases of FGR (ultrasound-estimated fetal weight less than the 10th or abdominal circumference less than the 5th percentile for gestational age) without fetal Doppler abnormalities were identified from a fetal ultrasound database. The primary outcome was a composite of perinatal mortality and morbidity. The risk of the primary outcome for each gestational age was compared with pregnancies delivered at 39 0/7 to 40 6/7 weeks. Odds ratios were adjusted for potential confounders., Results: The analysis included 1,024 pregnancies. FGR was identified at a median of 23 5/7 weeks (range: 20-42 weeks). Four cases of fetal death (23 4/7 -37 6/7 weeks) and no neonatal deaths were included. The primary outcome occurred in 209 patients (20.4%). This was greater for patients delivered at less than 37 weeks' gestation than for those delivered at or after 39 weeks' gestation, with no increased risk after 40 weeks., Conclusion: Among pregnancies complicated by suspected FGR without Doppler abnormalities, delivery at 39 weeks is safe with no difference in perinatal outcomes from 37 to 42 weeks., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Neuronostatin, a newly identified anorexigenic peptide, is present in the central nervous system. We tested the hypothesis that neuronostatin neurons are activated by feeding as a peripheral factor and that the glutamatergic system has regulatory influences on neuronostatin neurons. The first set of experiments analyzed the activation of neuronostatin neurons by refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: the fasting group, refeeding group, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)+refeeding group. We found that refeeding increased the phosphorylated signal transducers and transcription activator-5 (pSTAT5) expression in neuronostatin-positive neurons and that the CNQX injection significantly suppressed the number of pSTAT5-expressing neuronostatin neurons. The second set of experiments analyzed the activation pathways of neuronostatin neurons and the regulating effects of the glutamatergic system on neuronostatin neurons. The animals received intraperitoneal injections of glutamate receptor agonists (kainic acid, α-amino-3-hydroxy-5methyl-4-isoazepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA)) or 0.9% NaCl. The number of c-Fos-expressing neuronostatin neurons significantly increased following the AMPA and NMDA injections. In conclusion, we found that the neuronostatin neurons were activated by peripheral or central signals, including food intake and/or glutamatergic innervation, and that the glutamate receptors played an important role in this activation., Competing Interests: The authors declare no conflict of interest.

Noncollinear antiferromagnets can have additional spin Hall effects due to the net chirality of their magnetic spin structure, which provides for more complex spin-transport phenomena compared to ordinary nonmagnetic materials. Here we investigated how ferromagnetic resonance of permalloy (Ni&#95;{80}Fe&#95;{20}) is modulated by spin Hall effects in adjacent epitaxial IrMn&#95;{3} films. We observe a large dc modulation of the ferromagnetic resonance linewidth for currents applied along the [001] IrMn&#95;{3} direction. This very strong angular dependence of spin-orbit torques from dc currents through the bilayers can be explained by the magnetic spin Hall effect where IrMn&#95;{3} provides novel pathways for modulating magnetization dynamics electrically.

Aim: Breast cancer is the most common cancer and the second leading cause of cancer-related deaths among women. Several genetic and environmental factors are known to be involved in breast cancer pathogenesis, but the exact etiology of this disease is complicated and not completely understood. We aimed to investigate whether the gene polymorphisms of ABCB1 and ABCG2 carrier proteins and COX-2 enzyme affect breast cancer risk., Method: ABCG2 C421A (rs2231142), ABCB1 C3435T (rs1045642), COX-2 T8473C (rs5275) and COX-2 G306C (rs5277) were genotyped 104 breast cancer patients and 90 healthy controls using a real-time PCR for breast cancer susceptibility., Results: Patients carrying ABCG2 C421A , the CC genotype, had a higher risk of disease compared with patients carrying any A allele (OR = 3.06; 95% CI = 1.49-6.25, p  = 0.0019). The other variants showed no association with breast cancer (p > 0.05). Comparing the pathological parameters with the variants, only, the frequency of C allele of ABCB1 C3435T was significantly lower in the estrogen receptor-α (ERα) (OR = 2.25; 95% CI: 0.75-6.76; p  = 0.041) and progesterone receptor (PgR) (OR = 3.67; 95% CI: 1.34-10.03; p  = 0.008) positive breast cancer patients., Conclusion: ABCB1 C3435T and ABCG2 C421A might represent a potential risk factor for breast cancer for Turkish women., (© 2019 The Author(s).)

Background: Gunshot injury of the hip joint was reported to constitute 2-17% of all extremity firearm injuries. However, there are few studies in the literature related to gunshot injuries of the hip joint. The aim of the current study was to present the results of 10 cases treated with arthroplasty following a gunshot injury to the hip joint together with the recommended treatment algorithm., Methods: Patients with a previous medical history of hip joint region gunshot injury who underwent total hip arthroplasty were retrospectively evaluated. Those with incomplete medical records or who were lost to follow-up were excluded. Patients were classified according to the severity of the previous gunshot injury to the hip joint region. Harris hip score (HHS) and Short Form-12 quality of life score were the main outcome measurements. Postoperative complications encountered during follow-up were recorded., Results: The mean age of the patients at the time of surgery was 29.9 years. The mean preoperative HHS was 25.2 points and it was 65.8 at the final follow-up. Patients with bullet fragments in the hip joint, classified as group 1, had better HHS, whereas those with contaminated hip joint with intestinal flora, classified as group 3, had worst HHS., Conclusion: Hip arthroplasty after hip joint gunshot injury is a good treatment choice in young patients to reduce pain and regain functions. However, very high infection rates can be seen in patients with accompanying intestinal injury.