Laparoscopic Approach To Treat a Hydrocele of the Canal of Nuck: A Case Report.

The hydrocele of the canal of Nuck is a rare medical condition that usually affects females during childhood and early adulthood. It is considered the female homolog to the testicular hydrocele in males, as they share similar pathophysiology. The condition is often underreported and considered an incidental finding. On many occasions, it is mistakenly diagnosed and even managed as an inguinal hernia. The hydrocele of the canal of Nuck is usually managed surgically, either by open surgery or laparoscopy. In this case report, we will discuss the hydrocele of the canal of Nuck diagnosed in a young adult female and provide a background, case presentation, and thorough discussion.

Deep learning-based automated bone age estimation for Saudi patients on hand radiograph images: a retrospective study.

PURPOSE: In pediatric medicine, precise estimation of bone age is essential for skeletal maturity evaluation, growth disorder diagnosis, and therapeutic intervention planning. Conventional techniques for determining bone age depend on radiologists' subjective judgments, which may lead to non-negligible differences in the estimated bone age. This study proposes a deep learning-based model utilizing a fully connected convolutional neural network(CNN) to predict bone age from left-hand radiographs. METHODS: The data set used in this study, consisting of 473 patients, was retrospectively retrieved from the PACS (Picture Achieving and Communication System) of a single institution. We developed a fully connected CNN consisting of four convolutional blocks, three fully connected layers, and a single neuron as output. The model was trained and validated on 80% of the data using the mean-squared error as a cost function to minimize the difference between the predicted and reference bone age values through the Adam optimization algorithm. Data augmentation was applied to the training and validation sets yielded in doubling the data samples. The performance of the trained model was evaluated on a test data set (20%) using various metrics including, the mean absolute error (MAE), median absolute error (MedAE), root-mean-squared error (RMSE), and mean absolute percentage error (MAPE). The code of the developed model for predicting the bone age in this study is available publicly on GitHub at https://github.com/afiosman/deep-learning-based-bone-age-estimation . RESULTS: Experimental results demonstrate the sound capabilities of our model in predicting the bone age on the left-hand radiographs as in the majority of the cases, the predicted bone ages and reference bone ages are nearly close to each other with a calculated MAE of 2.3 [1.9, 2.7; 0.95 confidence level] years, MedAE of 2.1 years, RMAE of 3.0 [1.5, 4.5; 0.95 confidence level] years, and MAPE of 0.29 (29%) on the test data set. CONCLUSION: These findings highlight the usability of estimating the bone age from left-hand radiographs, helping radiologists to verify their own results considering the margin of error on the model. The performance of our proposed model could be improved with additional refining and validation.

Prevalence and associated factors of clubfoot in the eastern province of Saudi Arabia: A hospital-based study.

BACKGROUND: Clubfoot, or congenital talipes equinovarus, is a widely recognized cause of disability and congenital deformity worldwide, which significantly impacts the quality of life. Effective management of clubfoot requires long-term, multidisciplinary intervention. It is important to understand how common this condition is in order to assess its impact on the population. Unfortunately, few studies have investigated the prevalence of clubfoot in Saudi Arabia. AIM: To determine the prevalence of clubfoot in Saudi Arabia via the patient population at King Fahad University Hospital (KFUH). METHODS: This was a retrospective study conducted at one of the largest hospitals in the country and located in one of the most densely populated of the administrative regions. RESULTS: Of the 7792 births between 2015 to 2023 that were included in the analysis, 42 patients were diagnosed with clubfoot, resulting in a prevalence of 5.3 per 1000 live births at KFUH. CONCLUSION: The observed prevalence of clubfoot was significantly higher than both global and local estimates, indicating a substantial burden in the study population.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects.

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

The Incidence of Devitalization of Vital Teeth Associated with Pathologies of the Jaws Following Surgical Intervention: A Mixed-case Study.

AIM: The purpose of this mixed-case study is to explore the incidence of pulp necrosis of vital teeth after surgical treatment of adjacent lesions of the jaws. MATERIALS AND METHODS: The records of 341 biopsies submitted to the institute's histopathology laboratory were reviewed to include cases that met the inclusion criteria. About 84 biopsies collected from patients during surgical enucleation of lesions in proximity to healthy vital teeth were included of which 22 patients were recalled. Adjacent teeth were examined clinically and radiographically to assess their pulpal and periapical status after at least 8 months of follow-up. RESULTS: There were 7 different pathological lesions diagnosed histologically. The follow-up period ranged between 8 and 72 months; 12 cases (54.6%) have developed pulpal necrosis for at least one tooth after surgical enucleation of the lesion. The other 10 cases (45.4%) showed normal responses to sensibility testing for all the teeth adjacent to the lesion. Ten out of the 12 cases (83%) that underwent pulpal necrosis were associated with odontogenic cysts, whereas the remaining 2 were associated with periapical granuloma and fibrous dysplasia. CONCLUSION: Pulp necrosis is high in vital teeth associated with lesions without pulpal involvement. These teeth may benefit from root canal treatment prior to surgical enucleation of the lesion, which may prevent impaired healing or recurrence of infection. CLINICAL SIGNIFICANCE: Careful treatment planning and thorough discussion should take place between the surgeons, endodontists, and patients prior to executing the treatment. The patient should be aware that there is a possibility that they may need root canal treatment as a preventative measure to enhance the chances of healing following the surgical procedures and in case the patients opted not to perform root canal treatment beforehand, close follow-up in the future should take place to monitor the vitality of the teeth in the follow-up visits.

A Challenging Case of Heart Displacement by a Large Mediastinal Germ Cell Tumor.

Mediastinal germ cell tumors (GCTs) are rare and aggressive cancers originating from the germ cells in the mediastinum. Early detection and treatment are vital due to their high potential for metastasis and recurrence. We present a case of a 28-year-old man who exhibited a cough and shortness of breath. Laboratory tests revealed elevated tumor markers, alpha-fetoprotein, and beta-human chorionic gonadotropin. Imaging studies displayed a large mediastinal mass, causing the right displacement of the mediastinum and cardiac tamponade. The biopsy confirmed a non-seminomatous GCT, specifically a yolk sac tumor. The patient experienced pericardial effusion and cardiac tamponade after receiving two cycles of etoposide and cisplatin chemotherapy. To relieve the tamponade, an emergency pericardiocentesis was performed malignant GCTs necessitate prompt diagnosis and treatment and utilizing multimodal therapy such as chemotherapy to achieve tumor control. Due to the high risk of metastasis, vigilant surveillance for recurrence is essential, emphasizing the need for specific criteria for accurate early detection.

FOXO 1 deletion in chondrocytes rescues diabetes-impaired fracture healing by restoring angiogenesis and reducing apoptosis.

Introduction: Diabetes mellitus is associated with higher risks of long bone and jaw fractures. It is also associated with a higher incidence of delayed union or non-union. Our previous investigations concluded that a dominant mechanism was the premature loss of cartilage during endochondral bone formation associated with increased osteoclastic activities. We tested the hypothesis that FOXO1 plays a key role in diabetes-impaired angiogenesis and chondrocyte apoptosis. Methods: Closed fractures of the femur were induced in mice with lineage-specific FOXO1 deletion in chondrocytes. The control group consisted of mice with the FOXO1 gene present. Mice in the diabetic group were rendered diabetic by multiple streptozotocin injections, while mice in the normoglycemic group received vehicle. Specimens were collected 16 days post fracture. The samples were fixed, decalcified, and embedded in paraffin blocks for immunostaining utilizing anti cleaved caspase-3 or CD31 specific antibodies compared with matched control IgG antibody, and apoptosis by the TUNEL assay. Additionally, ATDC5 chondrocytes were examined in vitro by RT-PCR, luciferase reporter and chromatin immunoprecipitation assays. Results: Diabetic mice had ~ 50% fewer blood vessels compared to normoglycemic mice FOXO1 deletion in diabetic mice partially rescued the low number of blood vessels (p < 0.05). Additionally, diabetes increased caspase-3 positive and apoptotic chondrocytes by 50%. FOXO1 deletion in diabetic animals blocked the increase in both to levels comparable to normoglycemic animals (p < 0.05). High glucose (HG) and high advanced glycation end products (AGE) levels stimulated FOXO1 association with the caspase-3 promoter in vitro, and overexpression of FOXO1 increased caspase-3 promoter activity in luciferase reporter assays. Furthermore, we review previous mechanistic studies demonstrating that tumor necrosis factor (TNF) inhibition reverses impaired angiogenesis and reverses high levels of chondrocyte apoptosis that occur in fracture healing. Discussion: New results presented here, in combination with recent studies, provide a comprehensive overview of how diabetes, through high glucose levels, AGEs, and increased inflammation, impair the healing process by interfering with angiogenesis and stimulating chondrocyte apoptosis. FOXO1 in diabetic fractures plays a negative role by reducing new blood vessel formation and increasing chondrocyte cell death which is distinct from its role in normal fracture healing.

Polysplenia Syndrome Complicated by Splenic Infarction: A Report of a Rare Case.

Polysplenia syndrome is a rare congenital anomaly characterized by multiple spleens and associated organ anomalies, which can present with serious complications such as splenic infarction. Diagnosis and management of the disorder can be challenging due to the presence of associated anomalies and the condition is often diagnosed incidentally. We report a case of a six-year-old girl with no significant medical history who presented to the emergency department with fever, abdominal pain, and vomiting. Physical examination and laboratory investigations showed leukocytosis, anemia, and elevated levels of C-reactive protein. A computed tomography scan revealed splenic infarction with polysplenia syndrome. The patient received intravenous antibiotics and pain management and was closely monitored for complications such as sepsis. Early diagnosis and appropriate management are essential to prevent complications, and close monitoring and follow-up are necessary for long-term management.

A Novel Approach for Orthodontic Extrusion Prior to Intentional Replantation: A Case Report.

AIM: This case report aimed to present a novel surgical technique involving orthodontics luxation of the offended tooth using miniscrew prior to performing intentional replantation (IR) to remove an extruded separated instrument that injured the inferior alveolar nerve (IAN). BACKGROUND: Intentional replantation is a dental procedure that involves extracting a tooth, managing the root canal, and then reinserting the tooth back into its socket. This procedure is typically used as a last resort when other treatment options have failed or are not possible. Intentional replantation can be successful in preserving the tooth and preventing tooth loss, but it is important to note that there are risks involved. Maintaining the viability of the periodontal ligament (PDL) is a pivotal step to achieve a favorable outcome. CASE DESCRIPTION: A 15-year-old female patient came to the clinic complaining of electric-like pain in the left mandibular posterior area that radiated to the left ear and sometimes caused a headache. Upon clinical and radiographic evaluation, extruded endodontic file from the mesial root of the left first molar that penetrated the IAN canal was noticed. Nonsurgical root canal retreatment was performed, which failed to retrieve the separated file. Orthodontics luxation of the offended tooth was done 2 weeks before the surgical intervention using a miniscrew to induce PDL inflammation, which increased the tooth mobility and PDL volume, facilitating the atraumatic extraction and reduced the risk of complications, such as root resorption and ankylosis. Then, IR was performed, and the extruded file was successfully retrieved. Three months follow-up showed complete recovery of the endodontics-related IAN injury symptoms. Preapical radiographic evaluation and cone-beam computed tomography scan showed complete healing of the periapical radiolucency/area of low density and complete formation of the PDL space and lamina dura around the resected roots. CONCLUSION: This novel approach using a miniscrew suggests a noninvasive technique that minimizes the damage to the offended tooth surrounding tissues as well as minimizing the morbidity of the adjacent teeth and the vital anatomical structures. CLINICAL SIGNIFICANCE: Multidisciplinary comprehensive preplanning of complicated cases is essential to maximize treatment efficiency. The orthodontic extrusion facilitates the extraction process that helps in preserving the PDL, and ultimately increases the survivability of the teeth. How to cite this article: Alharbi MA, Alghamdi BA, Alswajy WA, et al. A Novel Approach for Orthodontic Extrusion Prior to Intentional Replantation: A Case Report. J Contemp Dent Pract 2023;24(11):895-901.

Midgut Volvulus Evolving From Internal Herniation Following Roux-en-Y Gastric Bypass Surgery.

In the literature, midgut volvulus is a well-known surgical complication following gastric bypass surgery that is serious and necessitates an immediate intervention. Here, we report a case of internal herniation that was misdiagnosed twice but eventually managed appropriately. A 27-year-old male with a surgical history of Roux-en-Y gastric bypass came to the emergency department complaining of severe epigastric abdominal pain. Two months earlier, he had a similar pain which was treated with Helicobacter pylori eradication therapy. Despite completing the eradication therapy, the pain reoccurred. Computed tomography angiography showed a filling defect in the superior mesenteric artery that was followed by a diagnostic laparoscopy ending with internal hernia reduction. Physicians should consider internal herniation as a differential diagnosis for every patient with a history of gastric bypass surgery presenting with abdominal pain.

Generalized anxiety disorder symptoms during COVID-19 pandemic in Jazan, Saudi Arabia.

The aim of this study was to measure anxiety levels and many co-factors that might influence the levels of anxiety during the COVID-19 outbreak in southern Saudi Arabia (KSA). A cross-sectional self-reporting survey was conducted to determine the level of generalized anxiety disorder (GAD) symptoms related to COVID-19 and quarantining. We selected a convenience sample of eligible participants who had been invited online through social media apps. The survey instrument was distributed, and 981 participants responded. Of the total sample, almost 90% were under the age of 40, 75% were women, and 77% had an educational level beyond high school. Just over half were single, with nearly all participants Saudi nationals. The overall prevalence of anxiety related to COVID-19 was 27%. Factors most strongly related to reporting anxiety included having a diagnosis of COVID-19, spending 1- ≥ 3 h focused on COVID-19, having a previous mental illness history, being a current or former smoker, being female, having a previous diagnosis of chronic or respiratory illness, being below age 40, having a limited standard of living, and being a student. Our study reveals how critical it is to emphasize preventive mental health care during pandemics and what factors may make some individuals most vulnerable to anxiety. Further research is recommended to examine GAD levels pre, during and post pandemic. Additional research to explore the long-term impact of the pandemic on mental health is also needed. being a student, and a limited standard of living.

Hospital Length of Stay and Related Factors for COVID-19 Inpatients Among the Four Southern Regions Under the Proposed Southern Business Unit of Saudi Arabia.

Objective: To assess the length of stay (LoS) variation for COVID-19 inpatients among the four regions of the Southern Business Unit (SBU). Methods: This is a comparative retrospective study of the LoS of COVID-19 inpatients in the four regions of the SBU in the KSA. Data was collected from the Ministry of Health (MoH) in all hospitals in the SBU. Participants were all patients admitted with confirmed COVID-19 between March 2020 and February 2021. Variables included region (variable of interest), demographics, comorbidities, and complications. Multilinear regression was performed to control for any factors that might have had an association with LoS. Results: The mean LoS of the total sample was 10 days and Bisha (the reference) was 7 days. Compared to Bisha, LoS in Jazan was 34% longer, in Najran 62% longer, and Aseer 40% longer. We observed that other factors also had an association with LoS, compared to Bisha, compared to the references, Saudi patients had a 15% shorter stay; admission to ICU increased LoS by 57%; patients who died during hospitalization had a 39% shorter LoS; the complications from COVID-19 of acute kidney injury and ARDS increased LoS by 22% and 48% respectively. Conclusion: After statistically controlling for confounders, this study reveals that LoS was significantly impacted by region in the SBU in the KSA. We recommend that further study be conducted to illuminate the underlying causes of this variation which may be organizational or structural to ensure high quality of care, access to care, and equity of resources throughout all regions of the SBU in accordance with the new Model of Care in Vision 2030.

Hypothyroidism and the risk of coronary artery disease in Saudi patients.

BACKGROUND: Hypothyroidism has been described in the literature as a risk factor for coronary artery disease (CAD). An association between thyroid-stimulating hormone (TSH) levels and CAD has been confirmed. In Saudi Arabia, there has been no study on the relationship between hypothyroidism and CAD. Therefore, the aim of this study was to investigate the prevalence and risk factors of CAD in patients with hypothyroidism. MATERIALS AND METHODS: This cross-sectional study conducted at King Abdulaziz Medical City in Riyadh (KAMC-R), included 412 adult hypothyroid patients who were followed up between 2013 and 2018. The data was collected on demographics, CAD-related risk factors, and hypothyroidism. In addition, relevant laboratory tests, including thyroid function tests, lipid profile, and hemoglobin A1c, were collected. SPSS version 28.0 was used for data analysis. Categorical data were presented as frequencies and percentages, while mean and standard deviations were computed for the numerical data. Student's t-test used to test statistical significance for numerical variables and Chi- square test was performed to test the differences between categorical variables. Multivariate binary logistic regression was used to determine the effects of gender, BMI, family history (CAD), smoking, hypertension, and TSH on CAD. RESULTS: Of the 412 hypothyroid patients, 21.8% were diagnosed with CAD, with more prevalence in men (44.15%) than in women (15.4%). About 46% had hypertension, 2.2% were smokers, and 2.4% had family history of CAD. Older age was significantly associated with a higher prevalence of CAD compared to younger age groups. The mean of TSH was significantly higher in CAD patients than non-CAD patients before and at diagnosis with CAD (P < 0.001). For every 1mIU/L increase in the TSH level, the odds of developing CAD increased significantly by 4.8% (P = 0.014). The odds ratios for other CAD risk factors were 3.13 for males, 8.1 for smoking, 2.48 for hypertension, and 9.9 for family history of CAD (P < 0.05). CONCLUSION: The prevalence of CAD in hypothyroid patients was higher than in the general population. TSH level was significantly associated with CAD. Male gender, older age, smoking, hypertension, family history of CAD, and high TSH level increased the likelihood of developing CAD.

FOXO1 expression in chondrocytes modulates cartilage production and removal in fracture healing.

Fracture healing is a multistage process characterized by inflammation, cartilage formation, bone deposition, and remodeling. Chondrocytes are important in producing cartilage that forms the initial anlagen for the hard callus needed to stabilize the fracture site. We examined the role of FOXO1 by selective ablation of FOXO1 in chondrocytes mediated by Col2α1 driven Cre recombinase. Experimental mice with lineage-specific FOXO1 deletion (Col2α1Cre+FOXO1L/L) and negative control littermates (Col2α1Cre-FOXO1L/L) were used for in vivo, closed fracture studies. Unexpectedly, we found that in the early phases of fracture healing, FOXO1 deletion significantly increased the amount of cartilage formed, whereas, in later periods, FOXO1 deletion led to a greater loss of cartilage. FOXO1 was functionally important as its deletion in chondrocytes led to diminished bone formation on day 22. Mechanistically, the early effects of FOXO1 deletion were linked to increased proliferation of chondrocytes through enhanced expression of cell cycle genes that promote proliferation and reduced expression of those that inhibit it and increased expression of cartilage matrix genes. At later time points experimental mice with FOXO1 deletion had greater loss of cartilage, enhanced formation of osteoclasts, increased IL-6 and reduced numbers of M2 macrophages. These results identify FOXO1 as a transcription factor that regulates chondrocyte behavior by limiting the early expansion of cartilage and preventing rapid cartilage loss at later phases.

Community-based observational assessment of compliance by the public with COVID19 preventive measures in the south of Saudi Arabia.

BACKGROUND: At the end of August 2020, a surge in the number of cases in the Jazan region has been observed. The number of reported cases by 19th of August in the Jazan region was more than 300, which exceeded the number of reported cases in larger regions such as Riyadh, and Makkah. This study aims to measure compliance by the public with COVID-19 preventive measures. METHODS: This study was a cross-sectional, field-based observational assessment of compliance by individuals in public settings with COVID-19 preventive measures in the Jazan region of Saudi Arabia. The assessment was performed in the last week of July 2020. The assessment was based on observing the actual compliance of individuals and different establishments in the Jazan region with COVID-19 preventive measures. To perform the field observations, a standardised check-list was adopted from COVID-19 preventive measures in the community, which was developed by the Saudi Centre for Disease Prevention and Control (CDC). RESULTS: A total of 1096 individuals were observed in 69 different locations in the Jazan region. Compliance by the observed individuals was variable depending on the age group, the setting and the recommended preventive practice. The findings indicate very low compliance of specific precautionary measures within public parks in comparison to other measured settings. Proportions of individuals not compliant with mask-wearing instructions varied according to settings and age group from 5% in malls and shopping areas to nearly 83% in public parks. Additionally, Proportions of children not compliant with mask-wearing instructions was higher in comparison to adults in all observed settings. CONCLUSIONS: The findings of this study identified variability in the levels of compliance with specific preventive measures against COVID-19. Further assessment is needed to explore factors associated with the limited observed compliance, in particular with regard to limited compliance to precautionary measures applied in specific settings and compliance of children to mask-wearing instructions.

A Case of Type 2 Sialidosis With Deletion of a Single Nucleotide at Position c.947 of the Neuraminidase 1 (NEU1) Gene.

Sialidosis is a rare, autosomal recessive inherited disorder caused by α-N-acetyl neuraminidase deficiency resulting from a mutation in the neuraminidase gene (NEU1), located on 6p21.33. A definitive diagnosis is made after the identification of a mutation in the NEU1 gene. An association exists between the impact of the individual mutations and the severity of the clinical presentation of sialidosis. Despite being uncommon, sialidosis has enormous clinical relevance due to its debilitating character. A complete understanding of the underlying pathology remains a challenge, which in turn limits the development of effective therapeutic strategies. We present a case of diagnosed congenital sialidosis type II.

Ki-67 labeling index in glioblastoma; does it really matter?

OBJECTIVE/BACKGROUND: Glioblastoma (GB) is the most common primary malignant brain tumor in adults. Ki-67 is a nonhistone nuclear protein that is expressed by cells entering the mitotic cycle and is associated with the transcription of ribosomal RNA (rRNA). In gliomas, the extent of expression of Ki-67 is roughly proportional to the histologic grade. Over the years, association studies were conducted trying to link the poor outcome in different types of malignant tumors to the Ki-67 proliferative index. This study is designed to investigate the relationship between the proliferation marker, Ki-67, and the overall survival amongst glioblastoma patients diagnosed between 2006 and 2012 at a single institution in Riyadh, Saudi Arabia. METHODS: This is a retrospective cohort study which investigated the status of Ki-67 labeling index in glioblastoma patients diagnosed at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 2006 and 2012. The Kaplan-Meier survival analysis was used to assess the overall survival (OS) and the Mantel-Cox log-rank test was used to compare the survival curves. Multivariate analysis using Cox proportional-hazards model was used to investigate other factors that might influence the overall survival. RESULTS: A total of 44 glioblastoma patients were included in the study. The median age at diagnosis was 56 (1-91) years. The 12-month survival rate for all glioblastoma patients was 48%. The median survival for patients with Ki-67 labeling index of ≤27%, and >27% was 11 months and 14 months, respectively. CONCLUSION: The difference between the survival curves of patients with Ki-67 labeling index of ≤27%, and Ki-67 of >27% was statistically insignificant (p = .130). Therefore, Ki-67 labeling index alone cannot predict survival in glioblastoma patients.

FOXO1 Deletion Reverses the Effect of Diabetic-Induced Impaired Fracture Healing.

Type 1 diabetes impairs fracture healing. We tested the hypothesis that diabetes affects chondrocytes to impair fracture healing through a mechanism that involves the transcription factor FOXO1. Type 1 diabetes was induced by streptozotocin in mice with FOXO1 deletion in chondrocytes (Col2α1Cre+FOXO1L/L) or littermate controls (Col2α1Cre-FOXO1L/L) and closed femoral fractures induced. Diabetic mice had 77% less cartilage and 30% less bone than normoglycemics evaluated histologically and by micro-computed tomography. Both were reversed with lineage-specific FOXO1 ablation. Diabetic mice had a threefold increase in osteoclasts and a two- to threefold increase in RANKL mRNA or RANKL-expressing chondrocytes compared with normoglycemics. Both parameters were rescued by FOXO1 ablation in chondrocytes. Conditions present in diabetes, high glucose (HG), and increased advanced glycation end products (AGEs) stimulated FOXO1 association with the RANKL promoter in vitro, and overexpression of FOXO1 increased RANKL promoter activity in luciferase reporter assays. HG and AGE stimulated FOXO1 nuclear localization, which was reversed by insulin and inhibitors of TLR4, histone deacetylase, nitric oxide, and reactive oxygen species. The results indicate that chondrocytes play a prominent role in diabetes-impaired fracture healing and that high levels of glucose, AGEs, and tumor necrosis factor-α, which are elevated by diabetes, alter RANKL expression in chondrocytes via FOXO1.

Pantoprazole reduces vascular relaxation in-vitro and ex-vivo and interferes with blood coagulation in an animal model.

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are effective antagonists of gastric acid secretion used to treat a number of gastro-esophageal disorders. The present study investigated the effect of Pantoprazole on vascular relaxation in-vitro and ex-vivo and its effect on blood coagulation in an animal model. MAIN METHODS: Isolated mouse arterial rings were pre-contracted in-vitro with phenylephrine and concentration-response curves to the acetylcholine relaxing effect were constructed in the presence of escalating concentrations of pantoprazole. In another set of experiments, male albino mice weighing ∼25 g were administered a daily dose of pantoprazole (0.4 mg by oral gavage) for four consecutive weeks; a vehicle control group was run in parallel. At the end of the treatment period, thoracic aorta was isolated for the assessment of vascular function ex-vivo. Blood samples were also collected to evaluate the effect of chronic pantoprazole therapy on coagulation parameters, namely, prothrombin time (PT) and activated partial thromboplastin time (aPTT). KEY FINDINGS: Vascular responsiveness to acetylcholine demonstrated a reduced relaxation of the arterial ring from baseline in the presence of different concentrations of pantoprazole (1 µM: 54.69 ±â€¯1.42%, 10 µM: 34.64 ±â€¯0.90% and 100 µM: 31.50 ±â€¯0.67% vs. control 74.39 ±â€¯1.426%, p < 0.001). Furthermore, acetylcholine-induced relaxation of the aorta was significantly diminished after four weeks of administrating pantoprazole to mice (37.12 ±â€¯2.50%) compared with the control group (72.47 ±â€¯1.68%, p < 0.001). This, however, wasn't accompanied by significant changes in the phenylephrine-induced vasoconstriction. Animals that received pantoprazole daily for four weeks also exhibited increased blood coagulation time in comparison to the vehicle control group (PT 45.30 ±â€¯3.52 s vs. 15.30 ±â€¯0.70 s, p < 0.05; aPTT 96.1 ±â€¯4.62 s vs. 48 ±â€¯1.97 s, p < 0.05, respectively). SIGNIFICANCE: The results of the present investigation suggest that pantoprazole reduces arterial relaxation and interferes with blood coagulation. Additional studies are warranted to assess the clinical implications of such observations.

Effect of ketamine on pro- and anti-inflammatory cytokine response in paediatric cardiac surgery: A prospective randomised controlled study.

BACKGROUND AND AIMS: Paediatric cardiac surgery with cardiopulmonary bypass (CPB) is associated with a marked inflammatory response and triggers release of inflammatory cytokines. The aim of this study was to study the effect of ketamine on the inflammatory response during correction of congenital cyanotic heart diseases. METHODS: Sixty-six patients with congenital cyanotic heart diseases scheduled for cardiac surgery were randomised into three groups. Group A patients did not receive ketamine (control group), Group B patients received 2 mg/kg ketamine intravenous (IV) and Group C patients received ketamine 2 mg/kg IV and an IV infusion of ketamine (50 µg/kg/min). Interleukin (IL) levels for IL-6, IL-8, IL-10, C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) levels were examined in the three groups at four timings: pre-operative (baseline), intraoperative (after weaning off the CPB) and post-operative (6 and 24 h after weaning off CPB). Paired sample t-test and ANOVA test were used for statistical analysis and P < 0.05 was considered statistically significant. RESULTS: Within each group, the intra- and post-operative serum levels of IL-6, IL-8, IL-10 and CRP were significantly elevated from the baseline, however, TNF-α was not significantly elevated. There were no statistically significant differences in the IL, CRP or TNF-α levels between the three groups. CONCLUSION: Paediatric cardiac surgery for congenital cyanotic heart disease is a triggering factor for the inflammatory response, yet we could not detect any beneficial effect of ketamine on that response whether given either as an IV induction dose or continued as an IV infusion.