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Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), which are endowed with beneficial biological activities as they reduce inflammation, regulate endothelial tone, improve mitochondrial function, and decrease oxidative stress. Therefore, inhibition of sEH for maintaining high EET levels is implicated as a new therapeutic modality with broad clinical applications for metabolic, renal, and cardiovascular disorders. In our search for new sEH inhibitors, we designed and synthesized novel amide analogues of the quinazolinone-7-carboxylic acid derivative 5 , a previously discovered 5-lipoxygenase-activating protein (FLAP) inhibitor, to evaluate their potential for inhibiting sEH. As a result, we identified new quinazolinone-7-carboxamides that demonstrated selective sEH inhibition with decreased FLAP inhibitor properties. The tractable SAR results indicated that the amide and thiobenzyl fragments flanking the quinazolinone nucleus are critical features governing the potent sEH inhibition, and compounds 34 , 35 , 37 , and 43 inhibited the sEH activity with IC 50 values of 0.30-0.66 μM. Compound 34 also inhibited the FLAP-mediated leukotriene biosynthesis (IC 50 = 2.91 μM). In conclusion, quinazolinone-7-carboxamides can be regarded as novel lead structures, and newer analogues with improved efficiency against sEH along with or without FLAP inhibition can be generated., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative ( 9 ), and most of the newly synthesized derivatives demonstrated moderate to good antiproliferative activities against a panel of hepatocellular carcinoma and breast cancer cells, exemplified with the diaryl isoxazole 11 and the diaryl pyrazole 85 with IC 50 values in the range of 0.7-9.5 μM. Treatments with both 11 and 85 induced apoptosis in these tumor cells, and they displayed antitumor activity in vivo in the Mahlavu hepatocellular carcinoma and the MDA-MB-231 breast cancer xenograft models, indicating that these compounds could be considered as leads for further development of antitumor agents. Important structural features of this compound class for the antitumor activity have also been proposed, which warrant further exploration to guide the design of new and more potent diaryl heterocycles., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A series of novel piperazine urea derivatives with thiadiazole moieties were designed, synthesized, and investigated for their inhibition potential against human fatty acid amide hydrolase (hFAAH). The urea derivatives possessing p-chlorophenylthiadiazole and benzylpiperazine fragments (19-22) were effective inhibitors of hFAAH. Notably, compounds with 4-chlorobenzyl (19) and 4-fluorobenzyl (20) tails at the piperazine side were identified as the most active inhibitors with IC 50 values of 0.13 and 0.22 µM, respectively. The preincubation test of 19 was in agreement with the irreversible binding mechanism. Molecular docking was performed to explore the potential binding interactions with key amino acid residues at the FAAH active site. These newly identified inhibitors could serve as leads for the further development of potent and selective FAAH inhibitors for FAAH-associated diseases., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Background: The pretreatment ratio of neutrophils to lymphocytes (NLR) has been suggested as an indicator of poor outcome in various cancers. This study aimed to determine whether the preoperative NLR may be a predictor of survival in patients who underwent curative resection for colorectal cancer (CRC)., Materials and Methods: The records of 219 CRC patients underwent curative resection between 2008 and 2014 were retrospectively evaluated. NLR was calculated by preoperative complete blood counts. The effects of age, gender, anatomic location, histologic grade, lymphovascular invasion, pathological T, pathological N, and tumor-node-metastasis stages and NLR on disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate analyses. The optimal cutoff value for NLR was determined using receiver operating characteristic curve analysis., Results: The best cutoff value of NLR was 2.8. Multivariate analysis showed that NLR was not a predictor of DFS. However, NLR was found as an independent prognostic factor for OS (Hazard ratio, 5.4; 95% confidence interval, 2.3-12.5; P = 0.0001)., Conclusion: A preoperative NLR of more than 2.8 might be an independent predictor for OS in patients with CRC. This simple and routinely available laboratory parameter may be used as a useful marker for identifying patients with a worse prognosis., Competing Interests: None

Objective: The aim of this study was to investigate whether being the parents of children with developmental hip dysplasia (DDH) is a risk factor for asymptomatic dysplasia., Methods: Asymptomatic parents of children who were diagnosed with DDH were assessed for presence of dysplasia by examining their anteroposterior pelvis radiographs at the neutral position. Eighty-six hips of 43 participants were included in the study group and 98 hips of 49 participants were included in the control group. Presence of hip dysplasia over the anteroposterior pelvis radiographs was analyzed for Wiberg's angle, acetabular index of the weight-bearing zone (the Tönnis angle), acetabular depth/width index, femoral head coverage ratio (FHCR) and femoral neck/shaft angle., Results: The mean acetabular depth/width ratio was 44.3% in the study group and 53.5% in the control group. And, the mean FHCR was 80% in the study group and 82% in the control group. There was a statistically significant difference between the two groups in terms of mean acetabular depth/width ratio (p < 0.05) and FHCR (p < 0.05). In addition, 21 participants in the study group and 2 in the control group had a pathological acetabular depth/width ratio. And, the number of participants with a pathological FHCR was 22 in the study group and 13 in the control group. A statistically significant difference was found between the two groups regarding the number of pathological measurements of acetabular depth/width ratio (p < 0.05) and FHCR (p < 0.05)., Conclusion: Having a parent with DDH is a definitive risk factor for the development of hip dysplasia in childhood. In addition, being a parent of a child with DDH is a risk factor for asymptomatic dysplasia. These parents should be screened by roentgenogram., Level of Evidence: Level III, Diagnostic Study., (Copyright © 2019 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study is to investigate which ADAMTS genes play a major role in the development of primary hip osteoarthritis, by comparing the tissue and blood samples in patients with hip osteoarthritis and a control group., Material and Methods: Human articular cartilage was obtained from femoral heads of 15 patients with end stage osteoarthritis undergoing total hip replacement. As the control group, the cartilages was obtained from femoral heads of 15 patients, who did not have osteoarthritis or degenerative changes in hip joint, undergoing hip replacement following the fracture of the femoral neck. After the cartilage samples were taken from the resection materials, the DNA polymorphisms in the patients' cartilage samples were tested by Polymerase Chain Reaction (PCR), the serum levels of aggrecanase genes were analyzed with Enzyme-Linked ImmunoSorbent Assay (ELISA)., Results: The level of ADAMTS5 and ADAMTS9 genes were found significantly lower as a result of ELISA analysis degenerative arthritis group than the control group (p < 0,05). ADAMTS 1, 4, 8, 15 were similar between the two groups in ELISA analysis (p > 0,05). As a result of quantitative real time RT-PCR analysis, the level of ADAMTS8 mRNA increased 3.5 fold in hip degenerative arthritis group when compared with femoral neck fractures group. ADAMTS1, ADAMTS4 and ADAMTS5 expression levels in hip degenerative arthritis group were decreased 2.5, 2 and 2.5 fold, respectively. ADAMTS9, 15 were found to be similar between two groups., Concluson: As a result of this study on hip osteoarthritis, the ADAMTS8 levels was found to be significantly higher in the end stage of hip osteoarthritis. Unlike similar studies on knee osteoarthritis, ADAMTS1,4,5 levels were found to be lower., (Copyright © 2018 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to define a sutureless peripheral nerve repair technique with a vein graft and bone marrow-derived stem cells (BMSC) and compare it to epineural repair., Materials and Methods: Thirty Wistar Albino rats were divided into five groups evenly. In the control group (C), epineural repair was performed. In the SV (suture + vein) and MSV (BMSC + suture + vein) groups, epineural repair was wrapped with a vein graft. In the V (vein) and MV (vein + BMSC) groups, sutureless repair using a vein graft was performed by taking sutures away from the regeneration site. Rats were evaluated with pinprick, toe spread tests and sciatic nerve index (SFI) at 4th, 8th, and 12th weeks. They were sacrificed at 12th week, repair sites were harvested and evaluated immunohistochemically., Results: There was no difference in pinprick and toe spread tests between the groups at 12th week. The mean SFI was -76.5 ± 3.7, -65.2 ± 11.7, -46.2 ± 19.4, -68.8 ± 9.8, -56 ± 8.8 in the C, SV, MSV, V, MV groups, respectively. The MSV group showed significantly the best SFI results (P < .05). NF-H immunostaining scores were as C; 1 ± 0.18, SV; 2.5 ± 0.36, MSV; 4 ± 0.49, V; 1.56 ± 0.54, MV; 3 ± 0.39, whereas GAP-43 scores were as C; 1 ± 0.31, SV; 2.66 ± 0.56, MSV; 4.50 ± 0.23, V; 2 ± 0.23, MV; 3 ± 0.6. The best nerve regeneration according to immunostaining results was observed in the MSV group (P < .05). The mean fibrosis area was 221.5 ± 25.9, 101.6 ± 7.1, 121.3 ± 18.8, 150.3 ± 12.1, 152.4 ± 11.8 μm 2 in the above groups, respectively. SV and MSV groups showed the significantly less fibrosis area (P < .05)., Conclusion: Epineural suture repair combined with vein wrapping and BMSCs (MSV) showed the best SFI, GAP-43, and NF-H immunostaining results., (© 2018 Wiley Periodicals, Inc.)

Background/aim: Pseudoangiomatous stromal hyperplasia (PASH) is a rare and benign mesenchymal proliferative breast lesion. Our aim is to review the clinical and radiological features of PASH and define a standard approach for its diagnosis and management. Materials and methods: Clinical records of 35 consecutive patients with PASH were retrospectively reviewed between 2009 and 2015. Patients with clinically or radiologically detected mass and patients who underwent biopsy for other indications and were diagnosed incidentally were included in the study. Results: There were 34 female patients and one male patient with gynecomastia. Twenty-three patients had palpable masses, and 16 of them were diagnosed as PASH with a median size of 3.1 cm. PASH did not show any specific features in radiological imaging. Core needle biopsy was performed for 3 patients before surgical excision; however, the lesions had not been diagnosed as PASH. In pathological examination, lesions associated with PASH showed nonproliferative changes in 14 patients, proliferative changes without atypia in 17, one phyllodes tumor, one in situ tumor, and one invasive cancer. Conclusion: Imaging findings of PASH are nonspecific. It is difficult to give a true prognostic diagnosis through pathological evaluation of big masses with core needle biopsy. We recommend surgical excision, especially for big lesions with suspicious features.

: There are only a few reports of total hip replacement in patients with hemophilia A and inhibitors. We performed total hip replacement in an 18-year-old adolescent boy who had high inhibitor titers since infancy. Recombinant factor VIIa (NovoSeven) was used as a bypass agent during the surgery. There was no excessive introperative bleeding; however, postsurgical bleeding occurred and was controlled by sequential administration of recombinant factor VIIa and activated prothrombin complex concentrate (FEIBA). This is the first report of this treatment modality in such a major surgery. Sequential bypassing agent therapy can be effective for treating refractory bleeding in hemophilia patients who have high inhibitor titers but require major surgery.

Objectives: This study aims to assess the mortality and morbidity rates of patients with intertrochanteric femoral fractures who were performed proximal femoral nail-antirotation (PFNA) or cemented, bipolar hemiarthroplasty with calcar replacement., Patients and Methods: A total of 127 patients (42 males, 85 females; mean age 79.2 years; range 55 to 98 years) who were treated due to proximal femoral fracture between January 2008 and January 2011 were compared retrospectively in terms of intraoperative mortality, total mortality, and monthly distribution of mortality rates. Of these 127 patients, 92 (28 males, 64 females; mean age 80.24 years; range 55 to 94 years) who were alive, who achieved at least a 12-month follow-up, and could walk and fulfil daily activities in preoperative period were included in the study. Patients were divided into two groups as PFNA group (n=34) and cemented, bipolar hemiarthroplasty with calcar replacement group (hemiarthroplasty group; n=58). Both groups were compared in terms of duration of operation, requirement for intraoperative blood transfusion, duration of hospital stay, functional outcomes, quality of life, complication and revision rates, and costs of operation., Results: Patients in both groups had the same type of fracture. Bone mineral densitometry results and the type and risk of anesthesia of both groups were similar. No significant difference was detected between two groups in terms of intraoperative mortality, total mortality, and monthly distribution of mortality rates (p>0.05). Mean durations of operation were 54.85 minutes (range 40-110 minutes) and 74.66 minutes (range 55-120 minutes) in the PFNA and hemiarthroplasty groups, respectively. Mean durations of hospital stay were 5.91 days (range 5-12 days) and 9.41 days (range 6-16 days) in the PFNA and hemiarthroplasty groups, respectively. In the PFNA group, durations of operation and hospital stay were shorter and functional results were superior (p<0.05). Requirement for blood transfusion was lower in the PFNA group., Conclusion: Both PFNA and cemented, bipolar hemiarthroplasty with calcar replacement are good techniques in treatment of intertrochanteric femoral fractures. Internal fixation may be more appropriate for elderly patients due to shorter duration of operation and lower risk of reoperation.

Objective: The aim of this study was to examine the role of sentinel lymph node biopsy (SLNB) on long-term disease outcome in patients with intermediate-thickness primary cutaneous melanomas., Materials and Methods: Forty patients with intermediate-thickness melanomas, defined as 1.0-4.0 mm, underwent SLNB between 1998 and 2011. The disease-free survival (DFS), overall survival (OS) and prognostic factors were analyzed., Results: Median age was 53 years (range: 24-74 years). Median Breslow thickness was 2.8 mm (range: 1.0-4.0 mm) and 27.5% were ulcerated melanomas. Median follow-up time was 70 months (range: 23-168 months). The number of patients with sentinel lymph node (SLN)-positive was 9 (22.5%) and completion lymph node dissection was performed in all of these patients. Ten patients (25%) developed distant and locoregional recurrence; 4 in the SLN-positive group (4/9; 45%) and 6 in the SLN-negative group (6/31; 19%), P < 0.042. In the SLN-negative group, one patient developed regional node recurrence; false-negative rate was 10%. SLN positivity and ulceration were independent prognostic factors for DFS in multivariate analysis (hazard ratio [HR] of 4.6, and 10.5, respectively; P < 0.011). For OS SLN positivity, ulceration and Breslow thickness were found to be the significant prognostic factors (HR of 5.4, 8.5 and 5.0, respectively; P < 0.024). Ten-year DFS and OS for SLN-negative and SLN-positive patients were 71%, 47% (P < 0.003), and 80%, 55% (P < 0.005), respectively., Conclusion: This study shows that survival rates are worse in the SLN-positive patients according to the long-term follow-up data. Ulceration and Breslow thickness also have significant effects on long-term survival in patients with intermediate-thickness primary cutaneous melanomas.

Objectives: This study aims to compare the efficiency and safety of intraarticular and intravenous tranexamic acid administration in patients who were performed primary total knee arthroplasty., Patients and Methods: This single center, randomized, controlled trial included 60 patients (8 males, 52 females; mean age 67.8 years; range 53 to 87 years) who were performed primary total knee arthroplasty by three surgeons due to a diagnosis of primary osteoarthritis between January 2015 and June 2015. Patients were separated into three groups. Patients in group 1 and group 2 were administered 2 g intravenous tranexamic acid and 2 g intraarticular tranexamic acid, respectively. Patients in group 3 were not administered tranexamic acid. Pre- and postoperative hemoglobin difference, volume of blood collected in drains, and transfusion rate were analyzed., Results: Compared with the control group, there was no significant difference between group 1 and group 2 in terms of total blood loss from the drain, pre- and postoperative hemoglobin difference, and the need for blood transfusion., Conclusion: Both intraarticular and intravenous administrations reduce blood loss and need for transfusion and there is no significant difference between the two techniques in terms of safety.

Congenital extremity anomalies are caused by pathological changes during the development process of the embryo. Exposure to toxins during 4-12 weeks of pregnancy may lead to extremity anomalies. In this article, we present a girl patient born as one of triplets at the 31st week and fifth day of pregnancy with meningomyelocele, Arnold-Chiari type 2 malformation, developmental dysplasia of the right hip, hypothyroidism, and lower extremity anomaly. Mother had a history of antenatal usage of sodium valproate. Radiographic examination of the lower extremity showed medial location of the fibula.

Introduction: We aimed to evaluate pathological extraspinal findings and congenital anomalies/anatomical variations that were incidentally detected on the magnetic resonance imaging (MRI) scans of intervertebral discs, to find the frequencies of these incidental findings, and to emphasise the clinical importance of them., Material and Methods: A retrospective study including 1031 consecutive patients (730 females and 301 males, with a median age of 46 years) was conducted by evaluating a total of 1106 MRI examinations of intervertebral discs. Examinations were performed with a 1.5 T MRI unit. Incidental findings were classified as pathological findings and congenital anomalies/anatomical variations., Results: The percentages of incidental extraspinal pathological findings and congenital anomalies/anatomical variations were 16.6% (95% confidence interval (CI): 14.4-18.8) and 3.7% (95% CI: 2.6-4.3), respectively. The percentage of incidental extraspinal pathological findings on cervical spinal MRI was 25.7% (95% CI: 20.1-31.7), thyroid nodules being the most common incidental findings. On thoracic spinal MRI (n = 19), inferior pole thyroid nodules were demonstrated as incidental extraspinal pathological findings, with a percentage of 10.5% (95% CI: 9.6-11.5). On lumbar spinal MRI, incidental pathological findings were detected with a percentage of 14.2% (95% CI: 11.9-16.6), while the percentage of congenital anomalies/anatomical variations was 4.8% (95% CI: 3.4-6.3). Eventually, 6.5% (95% CI: 2.6-9.4) of all cases with incidental extraspinal pathological findings underwent surgery., Conclusions: On MRI examination of intervertebral discs, paying attention to incidentally detected pathological extraspinal findings and congenital anomalies/anatomical variations is very important due to the fact that they can alter the treatment of the patient or affect the patient's life.

Objectives: This study aims to investigate the mid-term clinical and radiological results of cementless hydroxyapatite coated total hip arthroplasty (THA) for hip osteoarthritis due to developmental dysplasia of the hip (DDH)., Patients and Methods: Between January 2004 and December 2010, 34 hips (12 Crowe type I, 12 Crowe type II, 4 Crowe type III, 6 Crowe type IV) of 30 patients (22 females, 8 males; mean age 53.4 years; range 30 to 75 years) with degenerative arthritis due to DDH were analyzed in terms of cementless hydroxyapatite coated acetabular component (EPF Plus(®)) over Zweymüller femoral component (Zweymüller SL-PLUS(®)) and porous coating. Clinical assessment was performed using Harris hip scores (HHS) preoperatively and at the last clinic visit, while radiological assessment was done according to the Callaghan and Engh's criteria., Results: The mean follow-up was 48 months (range, 25-91 months). The mean HHS was 44.97 (28-55) preoperatively and 92.25 (69-100) at the last visit. All femoral components were graded as stable according to Callaghan and Engh's criteria. Radiolucency was mostly observed in Gruen zones 1 and zone 7 of the femur [zone 1; 20 hips zone 7; 19 hips zone 2; one hip, zone 3; one hip and zone 6 one hip]. Around acetabular component, radiolucency was detected in zone 2 in 12 hips, zone 3 in 10 hips and zone 1 in six hips. Heterotopic ossification developed in two hips, while neuropraxy was detected in two hips postoperatively. Femoral fissure in one hip, nonunion in the femoral osteotomy line in one hip, and femoral head autograft nonunion in one hip developed., Conclusion: Mid-term results of uncemented Zweymüller femoral stem and hydroxyapatite coated press-fit using acetabular components for THA femoral stem are excellent.

A 54-year-old male complained of a continuous pain together with an irreducible swelling of the left inguinal region 8 hours prior to admission to the surgical emergency department. His physical examination revealed a very painful, erythematous, irreducible swelling in the left inguinal region without abdominal peritoneal irritation. Routine blood tests disclosed mild leukocytosis. Abdominal plain X-ray film was not specific, and ultrasonography revealed a 10 cm in length inactive, edematous intestinal section within the inguinal hernia. With the diagnosis of strangulated inguinal hernia, he underwent surgical exploration through a transverse inguinal incision. By opening the hernia sac, 6-8 cc inflammatory fluid drained out, and an inflamed vermiform appendix adhered to the inner surface of the sac was seen. Appendicectomy and primary hernia repair were performed at the same time through the inguinal incision. The postoperative course was uneventful, and the histological examination of the specimen revealed an inflamed appendix.

Objectives: We evaluated the effects of glucosamine chondroitine sulphate (glcN-CS) on rat Achilles tendons in this experimental animal study., Materials and Methods: Thirty Wistar albino type rats weighing 300-350 g were randomly grouped into two. Group A: Achilles tendons were tenotomized, repaired and, glcN-CS given orally. Group B: Achilles tendons were tenotomized and repaired. All the rats were fed with pellet chow. Five rats in each group were sacrificed at 4, 8, and 12 weeks interval. Tensile strength of three tendon specimen from each group were tested biomechanically and two specimen were analysed histopathologically via immunohistochemical staining and hematoxylin and eosin staining. Contralateral side Achilles tendons were also grouped and analyzed as controls (group C and D)., Results: Histological results showed well organized collagen formation and less inflammation in group A. Biomechanical testing showed higher tendon strength in group A at eight weeks which is not statisticaly significant (55.3±4.84N, p=0.078). Rats which were were given glcN-CS had greater tendon strength which is statisticaly significant (50.01±5.62, p=0.014)., Conclusion: Glucoseamine chondroitine sulphate improved results of Achilles tendon healing in rats. This result might be due to decreased inflammation and stimulation of collagen synthesis. Although glcN-CS is recommended only in osteoarthritic patients to relieve symptoms and signs it can also be prefered in treatment of soft tissue injuries formed during sports activities.