Insulin resistance induced by de novo pathway-generated C16-ceramide is associated with type 2 diabetes in an obese population.

BACKGROUND: Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. METHODS: The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n = 20), obese-non-diabetic (n = 66), and obese-diabetic (n = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. RESULTS: C16-ceramide (P = 0.023), C16-dihydro-ceramide (P < 0.005), C18-dihydro-ceramide (P = 0.009) and C24-ceramide (P = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels (P = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 (P < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. CONCLUSIONS: The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.

Knowledge, attitude, and practice toward rheumatic fever and rheumatic heart disease among parents in Al-Baha Region, Saudi Arabia: A Cross-Sectional study.

Rheumatic fever (RF) is an autoimmune inflammatory process that develops as a sequela of untreated group A streptococcal pharyngitis and primarily affects children. It can lead to rheumatic heart disease (RHD), a major cause of cardiovascular morbidity and mortality. Awareness and preventive measures are crucial to mitigate its impact, particularly in low-resource settings. This study aimed to assess the knowledge, attitudes, and practices toward RF and RHD among parents living in Al-Baha Region. And to determine its association with other different sociodemographic variables. This was a cross-sectional study included 415 parents in Al-Baha region, Saudi Arabia. using a self-administered questionnaire distributed online. Of the total 415 participants, more than half were females 223 (53.7%), and 149 (35.9%) participants aged between 45 and 55 years. The knowledge regarding RF was classified as good 20 (4.8%), fair 104 (25.1%), and bad 291 (70.1%). The attitude towards RF showed that about half of the participants 206 (49.7%) had a negative attitude, 169 (40.7%) natural and 40 (9.6%) positive attitudes. While the total practice level was classified as Bad 15 (3.6%), Fair 113 (27.2%) and Good 287 (69.2%), females were more likely than males to exhibit good practices (p = 0.001). The study concluded that knowledge about RF and RHD among parents in the Al Baha region, Saudi Arabia, is very poor. Most participants lacked sufficient understanding of the definition of RF, its relationship with bacterial sore throats, prophylactic treatments, and the vulnerable age group. Attitudes towards RF were relatively negative. Therefore, healthcare authorities and providers should raise awareness and create educational programs to improve public understanding of RF and RHD, aiding in their prevention and control in the Al Baha region.

A rare primary hepatic neuroendocrine tumour with laparoscopic resection: a case report.

INTRODUCTION: Primary hepatic neuroendocrine tumours (PHNETs) are a rare form of hepatic neoplasms, and it is difficult to differentiate them from common hepatic malignancies in routine imaging studies. PRESENTATION OF THE CASE: We describe the case of a 60-year-old Indian male patient with a tentative preoperative diagnosis of hepatocellular carcinoma (HCC). Nevertheless, the definitive post-operative diagnosis was made by Histopathological and immunohistochemical assessment, which revealed a grade II neuroendocrine tumour (NET) of moderate differentiation. Surgical resection was performed through a minimally invasive approach with a favourable postoperative course and a short hospital stay. One-month Post-operative Octreotide scan showed no extrahepatic primary origin of the tumour. DISCUSSION: PHNET is a rare entity, and multi modalities investigations, including imaging, serology, endoscopy series, and histopathology findings, aside from long-term follow-up to rule out another primary origin, are essential for the final diagnosis of PHNET. Surgical resection stands as the mainstay of treatment of PHNETs. CONCLUSION: The absence of primary liver diseases should expand our possible differential diagnosis. Laparoscopic surgical resection of PHNETs carries a favourable outcome.

A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin.

The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubule length. Kinesin-13s are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerization activity, we created a synthetic ancestral kinesin-13 motor domain. This phylogenetically inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the kinesin-13 family. Here we show that the ancestral kinesin-13 motor depolymerizes stabilized microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied kinesin-13, MCAK and allows the ancestral kinesin-13 to depolymerize doubly stabilized microtubules and cause internal breaks within microtubules. These data suggest that the ancestor of the kinesin-13 family was a 'super depolymerizer' and that members of the kinesin-13 family have evolved away from this extreme depolymerizing activity to provide more controlled microtubule depolymerization activity in extant cells.

Invasive giant pancreatic desmoid-type fibromatosis with curative resection: A case report.

INTRODUCTION: Desmoid-type Fibromatoses (DTF) tumours are rare, benign fibrous tumours with aggressive invasive behaviour that account for approximately 0.03% of all neoplasms. We report the success in curing a rare, invasive, and huge pancreatic intraabdominal DTF. PRESENTATION OF CASE: A 42 years old male was medically free apart from recurrent left upper abdominal pain, anorexia, and nausea for more than ten years and no significant past surgeries, trauma, or family history of cancer. The patient has a non-tender large abdominal mass at the left hypochondria area extending down to the pelvis below the umbilicus with a rigid and smooth surface. The computed tomography scan showed a huge heterogeneous mass appears to be of pancreatic origin, measuring about 23 cm by 15 cm by 11 cm. The patient underwent radical antegrade modular pancreato-splenectomy, segmental transverse colectomy, adrenalectomy, and subsequent colo-colic anastomosis. The accurate gross size of the tumour specimen was 26 × 17 × 9 cm, and the weight was found to be 3.6 kg. Immunohistochemistry confirmed the diagnosis of pancreas DTF. The follow up to 5 years confirmed no recurrence reported clinically or by imaging. DISCUSSION: The Pancreas origin of DTF is a rarely reported subset with an incidence of around 5% of all DTF. Establishing the diagnosis is fundamentally based on the characteristic pathological and immunohistochemical studies, for the only available cure modality by complete radical resection to be promptly offered. CONCLUSION: Our case is rare and uniquely the largest pancreatic DTF reported in the literature with curative resection despite being locally invasive.

Gangliocytic Paraganglioma: A Rare Etiology of Obstructive Jaundice.

BACKGROUND Gangliocytic paraganglioma is an extremely rare tumor, with only 263 reported cases. This tumor has heterogeneous clinical presentation, with gastrointestinal bleeding being the most common. However, jaundice is a relatively unusual presentation, seen in less than 5% of all cases. CASE REPORT We report the case of a 32-year-old man who presented with abdominal pain and jaundice. He reported having similar episodes of this pain recently, but they were milder in severity. On examination, there was a tenderness in the right upper quadrant with a positive Murphy sign. Laboratory investigation revealed total bilirubin of 3.6 mg/dL with a direct bilirubin of 3.0 mg/dL, alkaline phosphatase of 323 IU/L, and g-glutamyltransferase level of 1153 IU/L, giving the impression of obstructive jaundice. The abdominal ultrasound examination revealed a normal common bile duct diameter with no thickening or pericholecystic fluid noted. Subsequently, the patient underwent endoscopic retrograde cholangiopancreatography, which revealed a mass in the second part of the duodenum. Histopathological examination of biopsy specimens obtained by fine-needle biopsy revealed an unencapsulated submucosal lesion with epithelioid, spindle, and ganglion cells. The spindle cells expressed positive immunohistochemical staining for S100, synaptophysin, and chromogranin. These findings were consistent with the diagnosis of gangliocytic paraganglioma. Surgical resection of the tumor was advised. However, the patient refused the operation despite the recommendation of the oncology team. CONCLUSIONS Gangliocytic paraganglioma is a very rare tumor that may present with a clinical picture mimicking a biliary disease. Clinicians should have a high index of suspicion for duodenal lesions in patients presenting with obstructive jaundice with no evidence of biliary stones.

Measurement Invariance and Differential Item Functioning Across Gender Within a Latent Class Analysis Framework: Evidence From a High-Stakes Test for University Admission in Saudi Arabia.

The main aim of the present study was to investigate the presence of Differential Item Functioning (DIF) using a latent class (LC) analysis approach. Particularly, we examined potential sources of DIF in relation to gender. Data came from 6,265 Saudi Arabia students, who completed a high-stakes standardized admission test for university entrance. The results from a Latent Class Analysis (LCA) revealed a three-class solution (i.e., high, average, and low scorers). Then, to better understand the nature of the emerging classes and the characteristics of the people who comprise them, we applied a new stepwise approach, using the Multiple Indicator Multiple Causes (MIMIC) model. The model identified both uniform and non-uniform DIF effects for several items across all scales of the test, although, for the majority of them, the DIF effect sizes were negligible. Findings from this study have important implications for both measurement quality and interpretation of the results. Particularly, results showed that gender is a potential source of DIF for latent class indicators; thus, it is important to include those direct effects in the latent class regression model, to obtain unbiased estimates not only for the measurement parameters but also of the structural parameters. Ignoring these effects might lead to misspecification of the latent classes in terms of both the size and the characteristics of each class, which in turn, could lead to misinterpretations of the obtained latent class results. Implications of the results for practice are discussed.

Economic impact of diabetic foot ulcers on healthcare in Saudi Arabia: a retrospective study.

BACKGROUND: Diabetic foot ulcers (DFU) are a critical complication of diabetes mellitus (DM) affecting life quality and significantly impacting healthcare resources. OBJECTIVE: Determine the direct medical costs associated with treating DFU in King Fahad Hospital of the University and identify factors that could assist in developing resource management guidelines in Saudi Arabia. DESIGN: Retrospective study. SETTING: SETTING: King Fahad Hospital of the University, Al-Khobar, Saudi Arabia. PATIENTS AND METHODS: The study included diabetic patients admitted with foot ulcerations between 2007 and 2017 inclusive. We determined management costs including drug usage, wound dressings, surgical procedures, admissions, and basic investigation. MAIN OUTCOME MEASURES: Factors affecting the direct perspective medical costs of managing DFU. SAMPLE SIZE: 99 patients. RESULTS: The overall cost of managing 99 patients with DFU was 6 618 043.3 SAR ($1 764 632.68 USD), which further translates to approximately 6684.9 SAR per patient/year ($1782.6 USD). The highest cost incurred was for admission expenditure (45.6%), followed by debridement (14.5%) and intensive care unit (ICU) admission (10.4%). CONCLUSION: The overall healthcare expenditure in treating DFU is high, with hospital admissions and surgical procedures adding a significant increase to the total cost. Focused patient education on overall glycemic control and prevention of DFU may decrease complications and hence, the overall cost. LIMITATIONS: Identified only the direct medical costs of DFU as the indirect costs were subjective and more difficult to quantify. CONFLICT OF INTEREST: None.

Metastatic testicular retroperitoneal teratoma in an adult: Case report.

INTRODUCTION: Teratomas are bizarre neoplasms derived from embryonic tissues typically found in the gonads and sacrococcygeal tissues of adults. CASE PRESENTATION: We report a case of histologically proven metastatic teratoma with an unusual presentation. The 32-year old male patient had a retroperitoneal tumour detected on computed tomography during the workup of abdominal pain. DISCUSSION: Retroperitoneal teratomas are uncommon and a challenge to manage. Differential diagnoses could be a dilemma without a thorough history and a high index of suspicion. CONCLUSIONS: Recurrent metastatic teratoma is one of the rare differential diagnoses of any retroperitoneal mass and can present years after complete resection of the primary tumour.

Effect of wet cupping on reducing bone pain for patients in King Abdulaziz University Hospital, Saudi Arabia. A retrospective study.

OBJECTIVES:  To investigate the effectiveness of wet cupping as alternative treatment on reducing bone pain and built a model that predicts the level of improvement for patients who suffer from bone pain. METHODS:  This retrospective study was conducted on 289 patients referred from specialty clinics to Prophetic Medicine Clinics (PMC) between September 2013 and August 2015. The effectiveness of cupping is assessed on patients with bone pain who were redirected to PMC, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. An artificial neural network (ANN) method was used to propose a model that predicts levels of improvement for patients suffering from bone pain. Therefore, a random sample of 90% of the data was used to build the ANN model and tested by the remaining 10%. Inferential statistics were conducted to study relations and compare blood tests before and after treatment. RESULTS: Out of 289 patients suffering from bone pain, more than 11% were completely cured, and 55% improved after wet cupping treatment sessions. The proposed ANN model showed a good performance with more than 72% accuracy. In addition, the statistical analysis showed a significant improvement for most blood tests. CONCLUSION: Wet cupping has positive effects on reducing bone pain. We recommend the use of an ANN model in PMC to predict whether patients will benefit from the treatment to reduce pain. This is a recommendation for further study not a conclusion.

Gastrointestinal stromal tumors. A clinicopathological study.

OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%). CONCLUSION: Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Cadaveric liver transplant from older donors.

OBJECTIVE: To examine the effects of cadaveric donor age on outcomes following orthotopic liver transplantation OLT. METHODS: Data were collected on all patients who underwent OLT between January 1997 and December 2004 at the Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. During this period, 313 OLTs were performed: 51 patients 16% received older donor livers OD; 60 or more years old, and 262 84% received younger donor livers YD; less than 60 years old. RESULTS: In the study group 313 patients, we found significantly more recipients of OD liver with blood group O: 51% versus 33% p=0.025 and with fulminant hepatic failure: 9.8% versus 5% p=0.018 compared to YD recipients. No difference between OD and YD liver recipients was found in initial poor graft function: 16/51 31% versus 74/262 28%, primary non-functioning: 6.5% versus 6.5%, the overall graft loss: 15/51 29% versus 62/262 24%, post-revascularization liver biopsy steatosis: 14/40 35% versus 82/232 36% or hepatic artery thrombosis: 1/51 2% versus 8/262 3%. There was no difference in graft actuarial survival between OD and YD recipients at 1, 3, and 5 years, 82% versus 87%, 75% versus 81%, and 75% versus 77% p=0.27 log rank or patient actuarial survival, 86% versus 89%, 79% versus 83%, and 79% versus 80% p=0.336 log rank. CONCLUSION: Orthotopic liver transplantation can be achieved with acceptable outcomes using selected livers from older deceased donors.

Cecal volvulus following mini gastric bypass: A case report and review of literature.

INTRODUCTION: With the rising worldwide obesity epidemic, bariatric surgeries are gaining popularity as the most effective modality for achieving long term results in weight loss and reducing its metabolic sequels. CASE PRESENTATION: A 36-year-old female presented with a sudden onset of severe abdominal pain for 6 h. The patient underwent Mini gastric bypass (MGB) 2 years prior to presentation. Computed tomography (CT) scan revealed a 14-cm dilatation of the cecum occupying the left upper quadrant of the abdomen with the swirling appearance of the mesentery. These findings were confirmed through emergency exploratory laparotomy to be cecal volvulus. a right hemicolectomy and conversion of MGB to a conventional Roux-en-Y gastric bypass. DISCUSSION: a modification of the classical gastric bypass surgery the MGB considered by its advocates to be a safer, simpler, and more effective option. However, serious complications can take place especially in the early learning curve of the procedure. CONCLUSIONS: We present a unexpected acute in top of chronic cecal volvulus in patient two years post MGB. The uncommon serious complication should be considered one of the differential diagnosis of acute surgical abdomen in those patients.

Management of Liver Trauma.

In the last 30 years, the management of liver injury has evolved significantly. The advancement of imaging studies has played an important role in the conservative approach for management. A shift from operative to nonoperative management for most hemodynamically stable patients with hepatic injury has been prompted by speed and sensitivity of diagnostic imaging and by advances in critical care monitoring. In this review article, the up-to-date recommendation on the management approach of liver trauma will be discussed.

The Prevalence of Hjortsjo Crook Sign of Right Posterior Sectional Bile Duct and Bile Duct Anatomy in ERCP.

AIM: The frequency of the Right Posterior Sectional Bile Duct (RPSBD) hump sign in cholangiogram when it crosses over the right portal vein known as Hjortsjo Crook Sign and the bile duct anatomy are studied. Knowledge of the implication of positive sign can facilitate safe resection for both bile duct and portal vein. METHODS: Prospectively, we included 237 patients with indicated ERCP during a period from March 2010 to January 2015. RESULTS: The mean age (±SD) and male to female ratio were 38.8 (±19.20) and 1 : 1.28, respectively. All patients are Arab from Middle Eastern origin, had biliary stone disease, and underwent diagnostic and therapeutic ERCP. Positive Hjortsjo Crook Sign was found in 17.7% (42) of patients. The sign was found to be equally more frequent in Nakamura's RPSBD anatomical variant types I, II, and IV in 8.4% (20), 6.8% (16), and 2.1% (5), respectively, while rare anatomical variant type III showed no positive sign. CONCLUSION: Hjortsjo Crook Sign frequently presents in RPSBD variation types I, II, and IV in our patients.

Acute Acalculous Cholecystitis Perforation in a Child Non-Surgical Management.

Spontaneous gallbladder perforation (SGP) is a rare but fatal complication usually associated with acute calculus cholecystitis. Mostly seen in adult patient and rarely reported in children. We report a rare case of aculcoulus gallbladder perforation in a 15 years old child post kidney transplant managed by percutaneous cholecystostomy tube drainage.