Students' perspectives on their early dropout of medical school.

BACKGROUND: Enrolling in medical school launches a more demanding and stressful way of life for newly admitted students. Some students will struggle academically and will ultimately drop out from medical school. The study aims to understand the perspectives that dropped-out students have and their opinion regarding possible preventative solutions. MATERIALS AND METHODS: This study uses a mixed-method approach. The results of students' examinations in the first 2 years of admission (within four academic years from 2016 until 2020) were collected from the medical school records. A questionnaire was developed to investigate the causes of early attrition during the study period. All dropped-out students who were admitted were included in this study. RESULTS: The study included 479 admitted students, 349 (72.9%) were females; 152 (31.7%) students dropped out in the premedical program (first two years); 104 (68.4%) of the dropped-out students were females. Thirty-five (23%) students responded to the questionnaire. Twenty-eight (80%) respondents believed that their low academic performance and leaving medical school was primarily related to psychological problems, 19 (54%) of respondents reported leaving for social reasons, and lack of self-organization in 13 (37.1%) respondents. Human anatomy was recorded as the most difficult course in the first year by 21 (63.6%) students. CONCLUSIONS: The cause of attrition is often multifactorial and complex. Psychological problems are one of the important factors in students with low academic performance and dropping out of the students. Some difficult courses in the curriculum may affect the students' academic performance leading to their attrition.

Relationship between admission selection tools and student attrition in the early years of medical school.

Objectives: Placement in medical schools is highly sought after worldwide with fierce competition among applicants. However, some of the best students withdraw after being accepted to medical school. The aim of this study was to investigate early student attrition within the first 2 years of medical school and determine its relationship to admission selection tools. Methods: Quantitative research was conducted at the College of Medicine and Health Sciences from 2016 until 2020, during which time routine admission data and students' examination results for the first 2 years were collected and analyzed. Results: The attrition rate during the study period was 31.7%. High school and college written examination scores were significantly related to completing the premedical program (p = 0.001 and p = 0.002, respectively). Female students scored significantly higher in multiple mini interviews (MMIs) compared with male counterparts (p < 0.001). However, the difference in MMI score was not related to student attrition (p = 0.148). Conclusion: The cause of early attrition is complex and cannot be attributed to a single factor.Undergraduate high school score and written admission examination results were statistically significant factors in relation to student attrition rate and low academic performance. The results of this study showed that the female students scored significantly higher in the multiple MMI tests compared to male students. However, MMI score alone was not significantly related to student attrition.

Long-Lasting Complete Remission in a Patient With Metastatic Metaplastic Breast Cancer Treated With Immune Checkpoint Inhibitor and Chemotherapy: A Case Report and a Review of the Literature.

Metaplastic breast cancer (MpBC) is a rare form of breast cancer known for suboptimal response to chemotherapy, high recurrence rate, poor prognosis, and limited treatment options. Recent studies have reported that MpBC has high expression of programmed death ligand 1 and tumor-infiltrating lymphocytes, indicating the potential effectiveness of immunotherapy (IO) in MpBC. In addition, several reports have demonstrated the activity of IO in MpBC. In this case report, we present a case of recurrent MpBC that achieved durable, rapid, complete remission with atezolizumab (anti-PD-L1) and nab-paclitaxel with a continued response even after discontinued therapy.

α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3ß, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades.

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3ß signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3ß, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested.

Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension.

Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks. The control rats were injected with the vehicle for the same period. The metformin-treated group received 200 mg/kg metformin daily for 10 weeks, beginning week 1, and received TAA injections with dosage and timing similar to those of the model group. All rats were culled at week 10. It was observed that TAA induced substantial renal injury, as demonstrated by significant kidney tissue damage and fibrosis, as well as augmented blood and kidney tissue levels of urea, creatinine, inflammation, oxidative stress, dyslipidemia, tissue inhibitor of metalloproteinases-1 (TIMP-1), and hypertension. TAA nephrotoxicity substantially inhibited the renal expression of phosphorylated AMPK. All these markers were significantly protected by metformin administration. In addition, a link between kidney fibrosis and these parameters was observed. Thus, metformin provides profound protection against TAA-induced kidney damage and fibrosis associated with the augmentation of the tissue protective enzyme AMPK and inhibition of oxidative stress, inflammation, the profibrogenic gene TIMP-1, dyslipidemia, and hypertension for a period of 10 weeks in rats.

Lower Prevalence of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma in Middle Eastern Population: Clinical Implications for Diagnosis and Prevention.

Introduction Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The prevalence of human papillomavirus (HPV) in HNSCC varies across regions. Objective This study aimed to determine the prevalence of high-risk HPV (hrHPV) among patients with HNSCC in the Middle East region. Methods Samples from patients with oropharyngeal or laryngeal lesions who underwent biopsy or resection at a tertiary care hospital from 2010 to 2015 were collected. Those confirmed as squamous cell carcinoma (SCC) on histopathology were identified as cases (n = 61), whereas benign lesions were used as controls (n = 83). Immunohistochemistry (IHC) for p16, p53, Ki-67, and in situ hybridization (ISH) for hrHPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66 were performed on all cases. Results A total of 154 cases were studied: 61 squamous cell cancers (cases), 83 benign lesions (control), and 10 dysplasia specimens. Among the cases, only five (8.6%) were positive for hrHPV, whereas only one control specimen tested positive. The SCC group had higher mean age, male sex, and history of cigarette smoking and alcohol usage. Among the hrHPV-positive SCC cases, 80% had a tumor in the oropharyngeal region. All hrHPV-positive cases were positive for p16 and p53 immunostains. Conclusion Among HNSCC cases, hrHPV was detected at a lower rate compared to other regions of the world. This study suggests that hrHPV plays a minor role in the pathogenesis of HNSCC in this region, compared to tobacco use and alcohol consumption.

Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression.

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects.

Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice.

Sirolimus (SRL) is widely used as an immunosuppressant to prevent graft rejection, despite the risk of impairing glucose metabolism. Metformin (MET) can reduce the detrimental effects of SRL in many patients, including diabetes and renal transplant recipients. Limited in vivo studies have reported on SRL and MET therapy, particularly in relation to cellular bioenergetics, glucose metabolism, and insulin resistance. Herein, we investigated the efficacy of SRL and MET co-treatment in BALB/c mice over 4 weeks. Balb/c mice (4-6 weeks old) were divided into four groups and injected intraperitoneally (i.p.) with water (control, CTRL), MET (200 µg/g), SRL (5 µg/g), or MET (200 µg/g) +SRL (5 µg/g) over a period of one month. We evaluated the body weight, food consumption rate, random blood glucose (BG), insulin levels, serum biochemistry parameters (ALT, Albumin, BUN, Creatinine), and histomorphology in all groups using standardized techniques and assays. All drug-treated groups showed a statistically significant decrease in weight gain compared to the CTRL group, despite normal food intake. Treatment with SRL caused elevated BG and insulin levels, which were restored with SRL + MET combination. Serum biochemical parameters were within the normal range in all the studied groups. SRL+ MET co-treatment decreased liver cellular respiration and increased cellular ATP levels in the liver. In the pancreas, co-treatment resulted in increased cellular respiration and decreased cellular ATP levels. Liver and pancreatic histology were unchanged in all groups. This study showed that co-treatment of SRL with MET alleviates hyperglycemia induced by SRL without any deleterious effects. These results provide initial insights into the potential use of SRL + MET therapy in various settings.

α-Bisabolol Attenuates NF-κB/MAPK Signaling Activation and ER-Stress-Mediated Apoptosis by Invoking Nrf2-Mediated Antioxidant Defense Systems against Doxorubicin-Induced Testicular Toxicity in Rats.

The present study investigated the effects of α-bisabolol on DOX-induced testicular damage in rats. Testicular damage was induced in rats by injecting DOX (12.5 mg/kg, i.p., single dose) into rats. α-Bisabolol (25 mg/kg, i.p.) was administered to the rats along with DOX pre- and co-treatment daily for a period of 5 days. DOX-injected rats showed a decrease in absolute testicular weight and relative testicular weight ratio along with concomitant changes in the levels/expression levels of oxidative stress markers and Nrf2 expression levels in the testis. DOX injection also triggered the activation of NF-κB/MAPK signaling and increased levels/expression levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and inflammatory mediators (iNOS and COX-2) in the testis. DOX triggered apoptosis, manifested by an increment in the expression levels of pro-apoptotic markers (Bax, Bcl2, cleaved caspase-3 and -9, and cytochrome-C) and a decline in the expression levels of anti-apoptotic markers (Bcl-xL and Bcl2) in the testis. Additionally, light microscopy revealed the changes in testicular architecture. α-Bisabolol rescued alterations in the testicular weight; restored all biochemical markers; modulated the expression levels of Nrf2-mediated antioxidant responses, NF-κB/MAPK signaling, endoplasmic reticulum (ER) stress, and apoptosis markers in DOX-injected testicular toxicity in rats. Based on our findings, it can be concluded that α-bisabolol has the potential to attenuate DOX-induced testicular injury by modifying NF-κB/MAPK signaling and the ER-stress-mediated mitochondrial pathway of apoptosis by invoking Nrf2-dependent antioxidant defense systems in rats. Based on the findings of the present study, α-bisabolol could be suggested for use as an agent or adjuvant with chemotherapeutic drugs to attenuate their deleterious effects of DOX on many organs including the testis. However, further regulatory toxicology and preclinical studies are necessary before making recommendations in clinical tests.

α-Bisabolol Attenuates Doxorubicin Induced Renal Toxicity by Modulating NF-κB/MAPK Signaling and Caspase-Dependent Apoptosis in Rats.

Doxorubicin (DOX) is a well-known and effective antineoplastic agent of the anthracycline family. But, multiple organ toxicities compromise its invaluable therapeutic usage. Among many toxicity types, nephrotoxicity is one of the major concerns. In recent years many approaches, including bioactive agents of natural origin, have been explored to provide protective effects against chemotherapy-related complications. α-Bisabolol is a naturally occurring monocyclic sesquiterpene alcohol identified in the essential oils of various aromatic plants and possesses a wide range of pharmacological properties such as antioxidant, anti-inflammatory, analgesic, cardioprotective, antibiotic, anti-irritant, and anticancer activities. The present study aimed to evaluate the effects of α-Bisabolol on DOX-induced nephrotoxicity in Wistar male albino rats. Nephrotoxicity was induced in rats by injecting a single dose of DOX (12.5 mg/kg, i.p.), and the test compound, α-Bisabolol (25 mg/kg) was administered intraperitoneally along with DOX as a co-treatment daily for 5 days. DOX-injected rats showed reduction in body weight along with a concomitant fall in antioxidants and increased lipid peroxidation in the kidney. DOX-injection also increased levels/expressions of proinflammatory cytokines namely tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) and inflammatory mediators like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and activated nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinases (MAPK) signaling in the kidney tissues. DOX also triggered apoptotic cell death, evidenced by the increased expression of pro-apoptotic markers like BCL2-Associated X Protein (Bax), cleaved caspase-3, caspase- 9, and cytochrome-C) and a decrease in the expressions of anti-apoptotic markers namely B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra large (Bcl-xL) in the kidney. These biochemical alterations were additionally supported by light microscopic findings, which revealed structural alterations in the kidney. However, treatment with α-Bisabolol prevented body weight loss, restored antioxidants, mitigated lipid peroxidation, and inhibited the rise in proinflammatory cytokines, as well as favorably modulated the expressions of NF-κB/MAPK signaling and apoptosis markers in DOX-induced nephrotoxicity. Based on the results observed, it can be concluded that α-Bisabolol has potential to attenuate DOX-induced nephrotoxicity by inhibiting oxidative stress and inflammation mediated activation of NF-κB/MAPK signaling alongwith intrinsic pathway of apoptosis in rats. The study findings are suggestive of protective potential of α-Bisabolol in DOX associated nephrotoxicity and this could be potentially useful in minimizing the adverse effects of DOX and may be a potential agent or adjuvant for renal protection.

Sirolimus treatment induces dose-dependent involution of the thymus with elevated cellular respiration in BALB/c mice.

Several in vitro and in vivo studies have shown that the mammalian target of rapamycin (mTOR) inhibitor sirolimus (rapamycin) suppresses thymus cellular respiration. The objective of this study is to investigate the chronic dose-dependent effects of sirolimus in the thymus. This was monitored using body weight, histomorphology, caspase-3 expression, cytochrome C immunohistochemistry, and cellular bioenergetics as surrogate biomarkers. BALB/c mice received intraperitoneal injections of either sirolimus (2.5, 5, or 10 µg/g) or dimethyl sulfoxide (0.1 µL/g) as a control for 4 weeks. At the end of the treatment, fragments were collected from the thymus, small intestine, adrenal gland, and kidney. They were processed for assessing histologic changes, measuring cellular respiration and ATP levels. Immunohistochemical stain of caspase-3 and cytochrome C was performed on paraffin-embedded tissue. The treated animals exhibited a dose-dependent reduction in weight gain despite adequate food intake. Sirolimus produced significant thymic derangements, manifested by dose-dependent tissue involution, increased cortical apoptotic bodies, increased caspase-3-positive lymphocytes, and increased rate of cellular respiration without a concomitant increase in cellular ATP. There were no similar changes in cellular ATP in the other assessed organs. The effects on thymic cellular bioenergetics suggest mitochondrial derangements, uncoupling of oxidative phosphorylation, and induction of apoptosis.

Copy Number Profiles of Prostate Cancer in Men of Middle Eastern Ancestry.

Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of genome-wide copy number profiles of 401 tumors of all ancestries. FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (2.3%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 × 10-3). Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those in men of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (two-sided proportion test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ motif-containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Larger studies investigating ME populations are warranted to confirm these observations.

Effect of angiotensin II on diabetic glomerular hyperpermeability: an in vivo permeability study in rats.

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg-1·min-1 for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ∼20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10-90 Å (Ficoll70-90 Å), were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (θ for Ficoll70-90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll70-90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.

1,2,3-Triazolyl ester of ketorolac (15K), a potent PAK1 blocker, inhibits both growth and metastasis of orthotopic human pancreatic cancer xenografts in mice.

More than 90% of human pancreatic cancers carry the oncogenic mutant of Ki-RAS and their growth depends on its downstream kinase PAK1, mainly because PAK1 blocks the apoptosis of cancer cells selectively. We developed a highly cell-permeable PAK1-blocker called 15K from an old pain-killer (ketorolac), that is shown here to inhibit the growth of three pancreatic cancer cell lines with IC50 values ranging 41-88 nM in vitro. The anti-cancer effect of 15K was further investigated in an orthotopic xenograft model with gemcitabine (GEM)-resistant human pancreatic cancer cell lines (AsPC-1 and BxPC-3) expressing luciferase in athymic mice. During 4 weeks, 15K blocks total burden (growth) of both AsPC-1 and BxPC-3 tumors (measured as radians/sec) with the IC50 below daily dose of 0.1 mg/kg, i.p. In a similar manner 15K reduced both their invasion and metastases as well, while it had no effect on either body weight or hematological parameters even at 5 mg/kg/day. To the best of our knowledge, 15K is so far the most potent among synthetic PAK1-blockers in vivo, and could be potentially useful for therapy of GEM-resistant cancers.

Possible acute rejection associated with the use of the new anti-hepatitis C virus medications.

Hepatitis C virus infection is associated with increased morbidity and mortality. It remains a major challenge for management and treatment, especially in patients with renal transplant. The new direct-acting antiviral agents gave big hopes to both clinicians and patients that they can overcome this challenge without major side effects. Studies recently have supported this claim; however, they are still few, limited, and may give false hopes. In the following case report, we present a case, supported by histological evidence about a possible acute rejection of kidney transplant after treatment with these new medications. This case is limited by the absence of donor-specific antibodies. This report is aimed to increase awareness about the urgent need for further studies.

Frequency of rare and multi viral high-risk HPV types infection in cervical high grade squamous intraepithelial lesions in a non-native dominant middle eastern country: a polymerase chain reaction-based pilot study.

BACKGROUND: The incidence of abnormal cervical smears in the United Arab Emirates (UAE) is 3.6%. Data regarding specific high-risk HPV (hrHPV) genotypes are insufficient. Identification of hrHPV subtypes is essential to allow formulating effective vaccination strategies. METHODS: A total of 75 archival cervical cone biopsies with HSIL or higher lesions (2012-2016) were retrieved from a tertiary hospital, including HSIL (n = 70), adenocarcinoma in-situ (n = 1) and squamous cell carcinoma (n = 4). Five tissue sections (10-µ-thick each) were cut and DNA extracted using the QIAamp DNA FFPE Tissue Kit. GenomeMeTM's GeneNavTM HPV One qPCR Kit was used for specific detection of HPV 16 and 18; and non-16/18 samples were typed by GenomeMeTM's GeneNavTM HPV Genotyping qPCR Kit. RESULTS: Median age was 34 years (range 19-58) with 70% UAE Nationals. hrHPV detected were 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, 66 & 68. hrHPV testing was negative in 12% of cases. Most common types were HPV 16 (49%), HPV 31 (20%) and HPV 18 (6.6%). hrHPV 16 and/or 18 represented 56% and rare subtypes 32%. Co-infection was present in 16%. Eight cases had two-viral subtype infections and 4 cases had 3 subtype infections. Multi-viral HPV infection was limited to hrHPV 16, 18, 31 & 33 subtypes. CONCLUSIONS: Infection by non HPV 16/18 is fairly common. A higher than expected incidence of rare subtype (20% hrHPV31) and multi-viral hrHPV (16%) were detected. This finding stresses the importance of this pilot study as currently only quadravalent vaccine is offered to control the HPV infection in the UAE population.

Gallbladder Polyps in Metachromatic Leukodystrophy.

BACKGROUND: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease, caused by a deficiency of arylsulfatase A, and leads to demyelination of the nervous system. A putative association between MLD and gallbladder pathology including malignancy is documented in the medical literature. CASE REPORT: A 10-year-old boy with MLD was found to have a papillary growth within a cystically dilated gallbladder. The lesion was confirmed to be papillomatosis/polyp with focal intestinal metaplasia. Dysplasia was not identified. CONCLUSION: MLD may be associated with a spectrum of gallbladder pathology including neoplastic conditions. Pathologists and clinicians should be aware of this association/risk. The patient may be offered regular ultrasound screening of the gallbladder.

Swim exercise training ameliorates hepatocyte ultrastructural alterations in rats fed on a high fat and sugar diet.

Excessive consumption of carbohydrate and fat increases the risk of liver disease. We hypothesized that swim exercise can protect hepatocytes from ultra-structural damage induced by high cholesterol and fructose diets (HCFD). Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. Swim exercise trained rats started the treatment from the 11th week until the sacrifice day, end of week 15. Blood samples were assayed for biomarkers of liver injury and adiponectin. The harvested liver tissues were examined using transmission electron microscopy (TEM). TEM images revealed substantial damage and accumulation of lipid droplets (steatosis) in the hepatocytes of the model group that was inhibited by swim exercise. In addition, HCFD significantly (p < 0.0005) increased insulin resistance index (HOMA-IR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), which were effectively (p < 0.02) decreased by a swim exercise to levels comparable to control group. Whereas, swim exercise increased adiponectin levels in HCFD group (p < 0.03). These results show that HCFD-induced hepatic injury is ameliorated by swim training exercise possibly via restoration of a normal blood sugar and lipid, induction of adiponectin and inhibition of inflammatory, and liver injury biomarkers.

Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer.

Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance.

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus - rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 µM) inhibited renal (22%, p = 0.002), hepatic (39%, p < 0.001), and cardiac (42%, p = 0.005) cellular respiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.