Investigation of the Efficacy of Bevacizumab Treatment in An Experimental Rat Model of Chronic Subdural Hematoma.

INTRODUCTION: Chronic subdural hematoma (cSDH), a condition that develops over time, is characterized by inflammation, angiogenesis, and membrane development. As the population's average age increases, the incidence of cSDH is expected to grow. While surgery is the primary treatment technique, medicinal therapy options are being explored for high-risk patients. Currently, the most effective therapy combination is dexamethasone (Dex) and atorvastatin (Ato); however, it is associated with an increased risk of mortality. This study explored the effects of bevacizumab (Bev), a VEGF antagonist, on cSDH. MATERIALS AND METHODS: Ninety-five rats were divided into four groups (n = 18): sham, control hematoma, Dex-Ato, and Bev. Two separate autologous blood injections into the subdural space were used as the model. Weight was monitored for all rats to assess changes in their overall health. The control group was given i.p. saline, the Dex-Ato treatment was given by gavage, and the Bev treatment was given i.p. On 7th, 14th and 21st days six rats from each group were sacrificed and analyzed, while 23 rats were excluded from the experiment. RESULTS: The maximum immunological response to cSDH was observed on day 14. Hematoma volume decreased over time in all groups. Dex-Ato and Bev were both found effective, while Dex-Ato caused weight loss. CONCLUSION: Bev had similar effects to the Dex-Ato group and was well tolerated by rats. Given that cSDH is a disease of the elderly and vulnerable populations, Bev may be a viable alternative that can shed light on the disease's etiology for future research.

Elecsys® AMH assay: Determination of Anti-Müllerian hormone levels and evaluation of the relationship between superovulation response in Holstein dairy cows.

BACKGROUND: Anti-Müllerian Hormone (AMH) serves as a crucial parameter in assessing the reproductive herd life and ovarian reserve in cattle. Consequently, extensive research is conducted on AMH levels. Various measurement methods can be employed to determine AMH levels. However, to our knowledge, no study has been conducted on Holstein donors using the Elecsys® AMH kit. OBJECTIVE: This study was designed to determine AMH levels in donors utilising the Elecsys® AMH kit and to evaluate the relationship between superovulation response parameters and AMH levels. METHODS: In this study, we measured the serum AMH levels of 36 cows using the Elecsys® AMH automated assay before the superovulation protocol (1st sample) and FSH injections (2nd sample). The cows were categorised into three groups based on their AMH levels: low, medium, and high AMH. RESULTS: Positive correlations were identified between AMH and parameters associated with superovulation response. The high AMH level group exhibited significantly greater numbers of corpus luteum, total embryos, transferable embryos, and grade 1 embryos compared to the medium and low AMH groups (p < 0.05) There was no significant difference between AMH levels before the superovulation protocol and FSH injections(p > 0.05). Body condition score and parity did not significantly affect AMH levels in cows (p > 0.05). Also, AMH cut-off values for the number of corpus luteum, total embryo, and transferable embryos were detected as 234, 227, and 210 pg/mL, respectively. CONCLUSION: These findings demonstrate that a high serum AMH level has a positive influence on the superovulation response. AMH can be used as a reliable marker for the selection of donors in Holstein cows.

Comparison of blood ΒHBA measurement devices for diagnosis of subclinical pregnancy toxaemia in sheep: A field study.

Pregnancy toxaemia is a serious disease that occurs during the last trimester of pregnancy in sheep. Yet, in most cases, the disease may have a subclinical course. This study was aimed at comparing blood ßHBA measurement devices for diagnosis of subclinical pregnancy toxaemia in late pregnant sheep. In the study, a total of 50 blood samples were collected from Romanov (n = 30) and cross-bred Hamdani (n = 20) sheep. Blood ßHBA levels were measured using TaiDoc TD-4235 and CentriVet ßHBA hand-held meter. Randox ßHBA (Ranbut) assay was used as a reference laboratory method to compare hand-held meters. ßHBA value of 0.8 mmol/L was set as the cut-off value for diagnosis of subclinical pregnancy toxaemia. Statistical analyses were carried out using Minitab 21 and Jamovi software. In the study, the correlation of Randox-TaiDoc TD-4235 and Randox-CentriVet was .822 (p < .001) and .728 (p < .001), respectively. Based on the Ranbut assay, nine ewes out of 50 were diagnosed with subclinical pregnancy toxaemia. Specificity (detection of healthy ewes) and sensitivity (detection of ewes with subclinical pregnancy toxaemia) for TaiDoc TD-4235 and CentriVet hand-held meters were 100%, 77.8%, and 100%, 66.7%, respectively. In the receiver operating characteristic (ROC) analysis, areas under the ROC curve (AUC) were 0.976 and 0.920 for TaiDoc and CentriVet, respectively. Bland-Altman analysis revealed a bias of 0.092 mmol/L for TaiDoc and a bias of 0.132 mmol/L for CentriVet. TaiDoc hand-held meter shows a better correlation with the Randox Ranbut assay and greater sensitivity compared to the CentriVet hand-held meter. In conclusion, both TaiDoc and CentriVet hand-held meters can be securely used in the diagnosis of subclinical pregnancy toxaemia in sheep. For these reasons, subclinical pregnancy toxaemia and these devices will be evaluated within the scope of herd management programme in the sheep industry. It should also be taken into account that these conditions will affect the future fertility of the mother and offspring.

The effects of case/control ratio and sample size on genome-wide association studies: A simulation study.

BACKGROUND: Genome-wide association studies (GWAS) is a useful tool for the detection of disease or quantitative trait-related genetic variations in the veterinary field. For a binary trait, a case/control experiment is designed in GWAS. However, there is limited information on the optimal case/control and sample size in GWAS. OBJECTIVES: In this study, it was aimed to detect the effects of case/control ratio and sample size for GWAS using computer simulation under certain assumptions. METHOD: Using the PLINK software, we simulated three different disease scenarios. In scenario 1, we simulated 10 different case/control ratios with increasing ratio of cases to controls. In scenario 2, we did versa of scenario 1 with the increasing ratio of controls to cases. In scenarios 1 and 2, sample size gradually was increased with the change case/control ratios. In scenario 3, the total sample size was fixed to 2000 to see real effects of case/control ratio on the number of disease-related single nucleotide polymorphisms (SNPs). RESULTS: The results showed that the number of disease-related SNPs were the highest when the case/control ratio is close to 1:1 in scenarios 1 and 2 and did not change with an increase in sample size. Similarly, the number of disease-related SNPs was the highest in case/control ratios 1:1 in scenario 3. However, unbalanced case/control ratio caused the detection of lower number of disease-related SNPs in scenario 3. The estimated average power of SNPs was highest when case/control ratio is 1:1 in all scenarios. CONCLUSIONS: All findings led to the conclusion that an increase in sample size may enhance the statistical power of GWAS when the number of cases is small. In addition, case/control ratio 1:1 may be the optimal ratio for GWAS. These findings may be valuable not only for veterinary field but also for human clinical experiments.

The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.

Anti-Müllerian hormone: A novel biomarker for detecting bovine freemartinism.

The anti-Müllerian hormone (AMH) indicates ovarian reserve in cattle, maintaining a consistent trajectory post-puberty. In heterosexual pregnancies, the development of the Müllerian duct in female foetuses is inhibited, resulting in an anticipated minimal or absent ovarian reserve capacity. This investigation aimed to compare AMH levels in healthy Holstein heifers that had reached puberty with those of freemartin animals of the same breed and age. The study incorporated Holstein heifers reaching puberty between 11 and 15 months of age in Group 1 (G1, n = 20) and freemartin animals in Group 2 (G2, n = 19, 16). AMH measurements (AMH-1/AMH-2) were recorded at 12-day intervals for the study participants. Notably, AMH levels in three freemartin animals could not be detected, prompting statistical analysis based on measurements from the remaining 16 freemartin animals in G2. A statistically significant correlation was observed between two separate measurements in G1 and G2 (p < .001). Furthermore, AMH-1 and AMH-2 levels were statistically higher in G1 than in G2 (p < .001). In G1, AMH-1 levels ranged from 227 to 677 pg/mL, with an average of 367.3 ± 25.5 pg/mL, and AMH-2 levels ranged from 234 to 645 pg/mL, with an average of 380.8 ± 24.4 pg/mL. Conversely, in G2, AMH-1 levels ranged from 10 to 72 pg/mL, with an average of 26.8 ± 4.44 pg/mL, and AMH-2 levels ranged from 12 to 68 pg/mL, with an average of 28.75 ± 4.18 pg/mL. The mean AMH levels in G1 were approximately 14 times higher than in G2 (p < .001). Consequently, ROC analysis utilizing AMH-1 and AMH-2 data established cut-off values of ≤72 and ≤ 68 pg/mL respectively for distinguishing freemartin animals. In conclusion, AMH could be used as a reliable biomarker for identifying Holstein freemartin animals.

Design and verification of a parallel elastic robotic leg.

This paper presents the design and experimental verification of a parallel elastic robotic leg mechanism that aims to capture the dynamics of the linear mass-spring-damper model. The mechanism utilizes a wrapping cam mechanism to linearize the non-linear force resulting from the elongation of the parallel elastic element. Firstly, we explain the desired dynamics of the mass-spring-damper model, including the impact transitions, and the design of the wrapping cam mechanism. We then introduce a system identification procedure to estimate the parameters of the leg mechanism corresponding to the dynamic model. The estimated parameters are tested with a cross-validation approach to evaluate the mechanism's performance in tracking the desired model. The experimental results show that the passive dynamics of the mechanism resemble the linear model as intended. Thus, the robot provides a basis for using parallel elastic actuation while using model-based controllers that benefit the analytic solutions of the linear model.

External validation of the "deformity, edema, and pain in pronation" model for predicting wrist fractures.

BACKGROUND: The aim of this study is to externally validate the "Deformity, Edema, and Pain in Pronation" model, which determines the necessity for radiography in patients with wrist trauma. METHODS: This prospective, cross-sectional study was performed in a tertiary emergency department (ED). All patients admitted to the ED with wrist trauma aged 18 years and older were included in the study. Patients who did not have acute and blunt wrist trauma, those who could not be fully examined due to various reasons, and patients who did not wish to participate were excluded. Each patient was examined by their responsible physician, and imaging tests were requested based on the indications. All radiographic images were evaluated by an orthopedic surgeon who was blinded to the clinical information. This evaluation was accepted as the standard reference for diagnosing fractures. RESULTS: 391 patients were included in the study. 170 patients (43.5%) had at least one fracture. The sensitivity and specificity of the model formed in our study in predicting wrist fractures were 98.77% (95% CI: 95.61-99.85) and 27.60% (95% CI 21.82-34.00), respectively. The area under the receiver operating characteristic curve (AUC) on external validation of the model was 0.878 (p < 0.001; 95% CI: 0.844-0.913). With the practice of this rule, there would be a 16% decrease in X-ray imaging request, while only 0.5% patients would have missed inoperable fractures. CONCLUSION: The "deformity, edema, and pain in pronation" model is a reliable and practical clinical decision rule for determining the necessity of radiography in wrist trauma.

Soranus of Ephesus (98-138 ad) and his contributions on human embryology, paediatrics and obstetric knowledge.

This study describes the life and works of Soranus of Ephesus (98-138 AD) who was born in Ephesus in Asia Minor and he practiced medicine in Alexandria and Rome in the Roman period (1st/2nd century AD). Although the majority of his writings have been lost, his surviving popular scientific textbook, a four-volume treatise on "Gynecology", describes ancient medical practice regarding human embryology, paediatrics and obstetrics.

Comparison of antegrade and retrograde cross pin fixation in the surgical treatment of pediatric supracondylar femur fractures: A biomechanical study.

PURPOSE: The aim of this study is to compare biomechanical stability of Kirschner wires (K-wires) sent with antegrade and retrograde technique in the fixation of pediatric supracondylar femur fractures. MATERIALS AND METHODS: A transverse fracture model was created two centimeters above the physis in 24 synthetic bone models suitable for the pediatric femur bone structure. The models were randomly divided into two groups as 12 bones each. In the first group (Group 1), 12 bone fracture models were retrogradely fixed with two cross K-wires. In the second group (Group 2), the fracture was fixed antegradely. In Group 2, both wire ends were allowed to protrude three millimeters from the femoral condyles. The stability of the groups was tested biomechanically by exposing them to varus and extension forces. The forces corresponding to 1 mm, 2 mm, 3 mm and 4 mm displacement and failure loads were calculated in two groups. RESULTS: According to the test results regarding displacements and failure loads, the retrograde group was found to be significantly stronger than the antegrade group against varus loads (p < 0.05). When the groups were compared in terms of extension strength, the results of the two groups were similar and there was no statistical difference between them (p > 0.05). CONCLUSION: Retrograde cross K-wires fixation provides a more stable fixation against varus forces. This is important to prevent varus deformity, which is a clinically less tolerable deformity. However, considering that full-weight mobilization of patients is not allowed after surgery in pediatric supracondylar femur fractures, the surgeon should consider that K-wires can also be sent antegrade to decrease the risk of septic arthritis.

Analysis of the factors affecting school attendance in pediatric fractures.

OBJECTIVE: This study aimed to examine the average duration of school absence according to the type of fracture and the factors affecting the duration of absence in children who had difficulty going to school after an acute orthopedic injury. METHODS: Patients between the ages of 6 and 17 who applied to the emergency department of our hospital and were treated for orthopedic trauma during a teaching period between September 2022 and December 2022 were examined. This study was designed prospectively. All school-aged patients with upper or lower extremity fractures requiring hospitalization or outpatient treatment were included in this study. Information about school absences and school starting dates were recorded at the outpatient clinical presentations of these patients. RESULTS: A total of 126 patients were included in this study. The mean age of the patients was 11.7 (range=6-17) years. The gender ratio was determined as F/M=20/106. The average time absent from school was 14.7 (range=2-61) days. Distal radius fractures were the most common upper extremity fractures; the mean time away from school was 7.9 days. In lower extremity fractures, lateral malleolar fracture was the most common complaint, and the mean duration of absence was calculated as 21.8 days. The periods of absence were mainly determined by the family or the child. CONCLUSION: One of the critical findings in this study was that rest periods were primarily determined by the parents and/or the child and not by the physician. The need to use crutches and/or transportation difficulties were other reasons for the absence. For these reasons, teachers and school management should be sensitive to the adverse effects of absenteeism on the child's success and provide facilitating support and home education opportunities when necessary. LEVEL OF EVIDENCE: Level II, Prognostic study.

Intraobserver and Interobserver Reliability of the Computed Tomography-Based Classifications Used in Posterior Malleolar Fractures: The Haraguchi and Bartonícek-Rammelt Classifications.

BACKGROUND: Three main computed tomography (CT)-based classification systems have been defined and used for posterior malleolar fractures. The intraobserver and interobserver reliability of two of these systems has never been investigated. The aim of this study was to investigate the intraobserver and interobserver reliability of the Haraguchi (HC) and Bartonícek-Rammelt (BRC) classifications. METHODS: Axial and sagittal CT sections and three-dimensional reconstruction images of 60 fractures were evaluated twice by six observers at a 6-week interval. Cohen κ values for intraobserver reliability and Fleiss κ values for interobserver reliability were calculated. RESULTS: The interobserver reliability of the HC was fair in both assessments (Fleiss κ: 0.263 and 0.249 for the first and second evaluations, respectively). The interobserver reliability of the BRC was moderate in both evaluations (Fleiss κ: 0.535 and 0.447, respectively). The intraobserver reliability values (Cohen κ) of the HC were determined to be between 0.532 and 0.927 for the six observers. These values indicated moderate agreement for one observer, substantial for four, and very good for one. Intraobserver reliability values for the BRC were determined to be between Cohen κ of 0.626 and 0.884. Based on these values, the BRC's intraobserver reliability indicated substantial agreement for two observers and very good for four observers. CONCLUSIONS: Intraobserver and interobserver reliability values of the BRC were higher than those of the HC.

Expression and localization of insulin-like growth factor gene family members in the caprine ovarian and uterine tissues during different pregnancy stages.

Goats are of significant economic importance, yet our knowledge of the molecular pathways involved in their pregnancy remains limited. This study aims to investigate the role of IGFs in uterine and ovarian cellular events during pregnancy in goats. Forty-two Hair Goats were examined, including four pregnancy groups representing embryo-positive (G1, n=7), early (G2, n=7), mid (G3, n=7), and late pregnancy (G4, n=7), as well as two luteal stage groups representing early (G5, n=7) and late (G6, n=7) phases. Uterine and ovarian tissues were collected, and RT-qPCR and immunohistochemistry were performed to evaluate IGF expression. The results showed that IGF1 and IGF2 expressions were significantly higher in G1 than in other pregnancy and control groups (p < 0.05). Additionally, IGFBP1 expression was higher in G2 than in G1 and G4 (p < 0.05), and IGFBP3 expression was higher in G4 than in any other pregnancy stage (p < 0.05). However, no statistically significant differences were observed in the expression levels of IGFBP4 and IGFBP6 between any of the groups. Finally, IGFBP5 expression was significantly higher in G1, G3, and G4 compared to G2 (p < 0.05). Overall, the dynamic changes observed in the expression of the IGF gene family during different stages of pregnancy highlight the crucial role of IGFs in regulating pregnancy in goats.

Differential expression of angiogenesis-related genes in goat uterus and corpus luteum during pregnancy.

Vascularization and the control of luteal and endometrial development are regulated by hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) during pregnancy. In this study, the mRNA and protein expression levels of HIFs (HIF1A, HIF2A and HIF3A) and VEGF in goat uterine and ovarian tissues during various stages of pregnancy were evaluated. A total of 42 Hair goats were used and were allocated into six groups, namely embryo-positive (G1), early pregnancy (G2), mid-term pregnancy (G3), late pregnancy (G4), oocyte-positive group (G5) and diestrus group (G6). The mRNA expression of the examined genes was evaluated by RT-qPCR, and protein expression was evaluated by immunohistochemistry (IHC). In caruncles, HIF1A mRNA expression was greater in G1, G2 and G4 than in G3 (p < .05). HIF1A and HIF2A expression was greater in G1 than in G5 (p < .05). In cotyledons, HIF1A, HIF2A and HIF3A mRNA expression was greater in G2 and G3 compared to G4 (p < .05). In luteal tissue, HIF1A mRNA expression was greater in G1 and G2 than in G3 and G4 (p < .05). In the immunohistochemical examination, HIF1A, HIF2A, HIF3A and VEGF immunoreactions were detected in uterine and luteal tissues. Findings suggest that HIFs and VEGF are involved in the regulation of ovarian functions as well as the processes of implantation and placentation.

Analysis of the Intra- and Inter-observer Reliabilities of Delbet Classification: Is Simplification Required.

Objective: This study aims to investigate the intra- and inter-reliabilities of Delbet classification and whether simplifying the classification improves reliability. Method: The Radiographs of 58 patients under 16 years old diagnosed with pediatric hip fractures between January 2012 and January 2020 were evaluated. Two separate Microsoft® PowerPoint (PPT) presentations consisting of 58 slides for Delbet's classification and its simplified form were prepared in which the order of cases was randomized and blinded. Then five orthopedic surgeons with different years of experience (more than 15 years of surgical experience were accepted experienced group) in pediatric trauma surgery evaluated the presentations two times one month apart. Results: In the inter-observer reliability analysis, a moderate agreement for the classical Delbet classification and a substantial agreement for the simplified Delbet classification was found in both evaluations. As a result of the intra-observer reliability analysis, there was substantial agreement in four observers, moderate agreement in one observer for the classical Delbet classification and substantial agreement in two observers, very good agreement in three observers for the simplified Delbet classification. The experience was not effective on agreement levels in the intra-observer reliability analysis of the classical Delbet classification system. The inter-reliability values of the less experienced group in the simplified classification were much higher than the classical Delbet classification. Conclusion: The simplification of the Delbet classification provides a significant increase in inter-observer reliability levels, especially in less experienced orthopedics and traumatology specialists, and a significant increase in intra-observer reliability levels. Level of Evidence: Level III, diagnostic study.

Clinical Outcomes of Two-Stage Implantation in Reverse Shoulder Arthroplasty for Postinfectious End-Stage Glenohumeral Arthritis in Native Shoulders: A Single-Center Cohort Study with a Minimum 2-Year Follow-up.

Background: Septic arthritis of the shoulder is a rare but devastating condition that may lead to joint destruction. There are few studies and limited outcome data on shoulder arthroplasty for infected native shoulders with end-stage glenohumeral arthritis (GHA). Hence, this study aimed to demonstrate the clinical outcomes of two-stage implantation in reverse shoulder arthroplasty (RSA) using an antibiotic spacer in the first stage for this challenging condition. Methods: We conducted a retrospective study on two-stage implantation in RSA in infected shoulders. Patients were diagnosed with end-stage GHA due to primary shoulder sepsis or infection following non-arthroplasty shoulder surgery. Laboratory data, range of motion (ROM), and functional scores including American Shoulder and Elbow Surgeons score, Constant score, and Disabilities of the Arm, Shoulder and Hand score were assessed prior to spacer placement and at the latest follow-up. Furthermore, intraoperative and postoperative complications were recorded. Results: In this study, 10 patients with a mean age of 54.8 ± 15.8 years (range, 30-77 years) were included. The mean follow-up period was 37.3 ± 9.1 months (range, 25-56 months). All postoperative ROM measurements and functional scores were improved significantly. Although no reinfection was observed, a total of 5 complications including 2 hematomas, 1 intraoperative humeral fracture, 1 humeral stem loosening, and 1 anterior deltoid dysfunction were observed in 4 patients after a follow-up period of at least 2 years after RSA. Conclusions: Two-stage implantation in RSA is an effective method for improving the function and controlling the infection in postinfectious end-stage GHA in native shoulders.

Analysis of the factors affecting pain level during K-wire removal among pediatric elbow fractures.

Our aim was, to analyze the reasons for possible increased pain during the removal of the Kirschner wires from the elbows of children. From February 2021 to December 2021, 573 patients with elbow fractures were treated. In total, 150 patients were analyzed prospectively. No action was taken to reduce pain during the removal of Kirschner wires. The pain status of the patients was evaluated according to the Wong-Baker FACES Pain Rating scoring system (WBAS), the Numeric Rating Scale (NRS) for the pain system and the pulse and oxygen saturation measured by the pulse oximeter on the finger. Measurements were performed before, during, immediately after and 30 min after the procedure. There were 119 patients with a diagnosis of supracondylar humerus fracture and 31 patients with a diagnosis of lateral condyle fracture. The mean age of treated patients was 7.1 years (1-15 years). Of the patients, 93 were boys and 57 were girls. In the measurements made according to the sex difference, it was determined that there was a statistically significant increase in the WBAS scores measured both before the procedure ( P = 0.032) and during the removal ( P = 0.017), and also in the pulse measurements taken 30 min after the removal in girls ( P = 0.034). A statistically significant difference was found in both the WBAS score during removal ( P = 0.025) and the NRS scores 30 min later ( P = 0.048) in the procedures performed on the right elbow. We found a statistically significant increase in the pain parameters we evaluated in girls, right extremity fractures, the group over 8 years old and when both parents were with the child during the K-wire removal procedure. In light of these findings, physicians should consider the above-mentioned conditions before starting the procedure to ensure a less painful and positive experience.