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.

Case Report: A Case of Leukocyte Adhesion Deficiency, Type III Presenting With Impaired Platelet Function, Lymphocytosis and Granulocytosis.

Fermitin family homolog 3 (FERMT3), alternatively kindlin-3 (KIND3), is an integrin binding protein (of 667 residues) encoded by the FERMT3 gene. The molecule is essential for activating integrin αIIbß3 (the fibrinogen receptor) on platelets and for the integrin-mediated hematopoietic cell (including platelets, T lymphocytes, B lymphocytes, and granulocytes) adhesion. Its defects are associated with impaired primary hemostasis, described as "Glanzmann's thrombasthenia (MIM#273800)-like bleeding problem." The defects are also associated with infections, designated as "LAD1 (leukocyte adhesion deficiency, type I; MIM#116920)-like immune deficiency." The entity that joins the impaired primary hemostasis with the leukocyte malfunction has been termed "leukocyte adhesion deficiency, type III" (LAD3, autosomal recessive, MIM#612840), representing a defective activation of the integrins ß1, ß2, and ß3 on leukocytes and platelets. Here, we report a male toddler with novel compound heterozygous variants, NM_178443.2(FERMT3):c.1800G>A, p.Trp600* (a non-sense variant) and NM_178443.2(FERMT3):c.2001del p.*668Glufs*106 (a non-stop variant). His umbilical cord separated at about 3 weeks of age. A skin rash (mainly petechiae and purpura) and recurrent episodes of severe epistaxis required blood transfusions in early infancy. His hemostatic work-up was remarkable for a normal platelet count, but abnormal platelet function screen with markedly prolonged collagen-epinephrine and collagen-ADP closure times. The impaired platelet function was associated with reduced platelet aggregation with all agonists. The expression of platelet receptors was normal. Other remarkable findings were persistent lymphocytosis and granulocytosis, representing defects in diapedesis due to the integrin dysfunction. The natural history of his condition, structure and sequence analysis of the variations, and comparison with other LAD3 cases reported in the literature are presented.

Early (5-Day) Onset of Diabetes Mellitus Causes Degeneration of Photoreceptor Cells, Overexpression of Incretins, and Increased Cellular Bioenergetics in Rat Retina.

The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission electron microscopy. Tissue localization of glucagon-like-peptide-1 (GLP-1), exendin-4 (EXE-4), and catalase (CAT) in non-diabetic and diabetic rat retinas was conducted using immunohistochemistry, while the retinal and plasma concentration of GLP-1, EXE-4, and CAT were measured with ELISA. Lipid profiles and kidney and liver function markers were measured from the blood of non-diabetic and diabetic rats with an automated biochemical analyzer. Oxygen consumption was monitored using a phosphorescence analyzer, and the adenosine triphosphate (ATP) level was determined using the Enliten ATP assay kit. Blood glucose and cholesterol levels were significantly higher in diabetic rats compared to control. The number of degenerated photoreceptor cells was significantly higher in the diabetic rat retina. Tissue levels of EXE-4, GLP-1 and CAT were significantly (p = 0.002) higher in diabetic rat retina compared to non-diabetic controls. Retinal cellular respiration was 50% higher (p = 0.004) in diabetic (0.53 ± 0.16 µM O2 min-1 mg-1, n = 10) than in non-diabetic rats (0.35 ± 0.07 µM O2 min-1 mg-1, n = 11). Retinal cellular ATP was 76% higher (p = 0.077) in diabetic (205 ± 113 pmol mg-1, n = 10) than in non-diabetic rats (116 ± 99 pmol mg-1, n = 12). Thus, acute (5-day) or early onslaught of diabetes-induced hyperglycemia increased incretins and antioxidant levels and oxidative phosphorylation. All of these events could transiently preserve retinal function during the early phase of the progression of diabetes.

Case Report: BCG-Triggered Hemophagocytic Lymphohistiocytosis in an Infant With X-Linked Recessive Mendelian Susceptibility to Mycobacterial Disease Due to a Variant of Chronic Granulomatous Disease.

In the United Arab Emirates, BCG (Bacillus Calmette-Guérin) is administered to all newborns. We present here a young infant with an inborn error of immunity (IEI) who developed fatal adverse events to this live-attenuated vaccine. This male infant received BCG (Serum Institute of India Pvt., Ltd., India) on Day 11 of life. On Day 25, he developed fever, followed by cervical lymphadenitis and bilateral otitis media with fluid drainage. On Day 118, he was admitted with severe hemophagocytic lymphohistiocytosis (HLH), and passed away on Day 145. The diagnostic exome sequencing test identified a hemizygous nonsense variant, NM_000397.3(CYBB):c.676C>T, p.Arg226* (rs137854592). Pathogenic variants of CYBB [cytochrome b(-245), beta subunit; Mendelian Inheritance in Man [MIM] accession code, 300481] are known to cause "immunodeficiency 34, mycobacteriosis, X-linked" (IMD34, MIM#300645) and "chronic granulomatous disease, X-linked" (CGDX, MIM#306400). The natural history of his illness is consistent with "X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD)." This entity is responsible for his BCG disease and is a likely trigger of his HLH. This disastrous event underlines the importance of developing worldwide policies that target BCG disease prevention, especially in communities with high prevalence of IEI. Moreover, screening for genetic causes of MSMD in the community could pave the way, at least partially, for scale-up of tuberculosis (TB) prevention.

Effects of Diabetes Prevention Education Program for Overweight and Obese Subjects with a Family History of Type 2 Diabetes Mellitus: A Pilot Study from the United Arab Emirates.

OBJECTIVES: The association of obesity and family history of type 2 diabetes mellitus (T2DM) provides an opportunity for risk stratification and prevention, as these two conditions are the most well-known risk factors for T2DM. We aimed to test the feasibility and effects of a diabetes mellitus prevention education program designed for overweight and obese Emirati people with at least one parent with T2DM. METHODS: We conducted a pilot study using a pre-post design without a control arm at the Diabetes Center at Tawam Hospital in Al Ain, UAE. Overweight and obese subjects with at least one parent with T2DM were invited to participate. Three study assessments were conducted at baseline, three months, and six months including a questionnaire, anthropometry, and laboratory assessments. Interventions included three individualized or family-engaged counseling sessions based on the DiAlert protocol. The study outcomes included awareness of risks and prevention opportunities to T2DM, behavior changes in nutrition and exercise, decreased waist-circumference, and clinical/metabolic/inflammatory markers. Pre-post changes were analyzed using repeated-measures analysis of variance. RESULTS: One hundred twenty-two overweight or obese individuals were approached. Forty-four individuals met the eligibility criteria, and 32 individuals (35.0±9.0 years; 75.0% female) completed the study. At six months, there were significant improvements in the glycated hemoglobin levels (p = 0.007), high-density lipoprotein (p < 0.049), serum creatinine (p < 0.025), estimated glomerular filtration rate (p = 0.009), and adiponectin levels (p < 0.024). Sixteen of 32 participants had ≥ 2 cm reduction in waist circumference. They demonstrated notable physical and laboratory improvements in moderate-vigorous activity, average activity counts per day, tumor necrosis factor-alpha, and interleukin-6 total cholesterol, triglyceride, and low-density lipoprotein. CONCLUSIONS: Offering family-oriented diabetes education to people at risk for T2DM is well received and has favorable effects on relevant risk factors. Better testing with large-scale randomized controlled studies is needed, and implementing similar educational programs for the Emirati population seems warranted.

Genetic variants of small airways and interstitial pulmonary disease in children.

Genetic variants of small airways and interstitial pulmonary disease have not been comprehensively studied. This cluster of respiratory disorders usually manifests from early infancy ('lung disease in utero'). In this study, 24 variants linked to these entities are described. The variants involved two genes associated with surfactant metabolism dysfunction (ABCA3 and CSF2RB), two with pulmonary fibrosis (MUC5B and SFTP), one with bronchiectasis (SCNN1B), and one with alpha-1-antitrypsin deficiency (SERPINA1). A nonsense variant, MUC5B:c.16861G > T, p.Glu5621*, was found in homozygous state in two siblings with severe respiratory disease from birth. One of the siblings also had heterozygous SFTPA1:c.675C > G, p.Asn225Lys, which resulted in a more severe respiratory disease. The sibling with only the homozygous MUC5B variant had lung biopsy, which showed alveolar simplification, interstitial fibrosis, intra-alveolar lipid-laden macrophages, and foci of foreign body giant cell reaction in distal airspaces. Two missense variants, MUC5B:c.14936 T > C, p.Ile4979Thr (rs201287218) and MUC5B:c.16738G > A, p.Gly5580Arg (rs776709402), were also found in compound heterozygous state in two siblings with severe respiratory disease from birth. Overall, the results emphasize the need for genetic studies for patients with complex respiratory problems. Identifying pathogenic variants, such as those presented here, assists in effective family counseling aimed at genetic prevention. In addition, results of genetic studies improve the clinical care and provide opportunities for participating in clinical trials, such as those involving molecularly-targeted therapies.

Novel genetic variants of inborn errors of immunity.

OBJECTIVES: Inborn errors of immunity (IEI) are prevalent in tribal cultures due to frequent consanguineous marriages. Many of these disorders are autosomal recessive, resulting from founder mutations; hence they are amenable to prevention. The primary objective of this study was to evaluate the pathogenicity of novel variants of IEI found among Emiratis. METHODS: This retrospective data collection study reports novel variants of IEI detected by diagnostic exome sequencing. Pathogenicity prediction was based on scoring tools, amino acid alignment, and Jensen-Shannon divergence values. RESULTS: Twenty-one novel variants were identified; nine were frameshift, three nonsense, four intronic (one pathogenic), and five missense (two pathogenic). Fifteen variants were likely pathogenic, of which 13 were autosomal recessive and two uncertain inheritance. Their clinical spectra included combined immunodeficiency, antibody deficiency, immune dysregulation, defects in intrinsic/innate immunity, and bone marrow failure. CONCLUSION: The described novel pathogenic variants are core to a planned national screening program that aims toward IEI prevention. Future studies, however, are needed to confirm their natural history in individual patients and estimate their prevalence in the community.

Perception of Cosmetic Procedures among Middle Eastern Youth.

BACKGROUND: In the past decade, there has been an increase in the number of cosmetic procedures performed globally. About one-third of individuals who undergo cosmetic procedures are under the age of 35. The United Arab Emirates (UAE) has become a regional hub for cosmetic procedures. This cross-sectional study examines the perception of cosmetic procedures among youth in the UAE. METHODS: A 63-question survey was electronically disseminated to university students to identify factors associated with the use of cosmetic procedures in this population. RESULTS: Ninety-one percent of the 178 participants were female, and 58 percent of them were aged 19 to 21. The majority of the participants felt cosmetic procedures are gaining acceptance in UAE society. Nearly 70 percent of participants felt that a legal and regulatory framework was important to determine the permissible age for undergoing cosmetic surgeries. LIMITATIONS: One limitation of the study lies in a modest response rate of 35.6 percent. There was a small number of male responders, and the assessment of differences between sex was not easy to conduct. CONCLUSION: Cosmetic procedures are increasingly being accepted among youth in the Middle East, with skin and nasal procedures being the most popular. The youth's concept of ideal body shape is in alignment with the Western ideas of beauty. Future research could characterize these perceptions in other cultures and explore differences in what is perceived to be beautiful in various parts of the world.

Adverse Events of the BCG (Bacillus Calmette-Guérin) and Rotavirus Vaccines in a Young Infant with Inborn Error of Immunity.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) and rotavirus vaccines are live-attenuated preparations. In the United Arab Emirates, these products are universally administered to the young infants. This unguided practice does not account for the children with immunodeficiency, which frequently manifests after the administration of these vaccines. We present here a young infant with immunodeficiency that developed disseminated tuberculosis infection and severe diarrhea due to these improper immunizations. Case Presentation. This young infant was diagnosed at six months of age with "immunodeficiency type 19" (MIM#615617) due to homozygous nonsense variant, NM_000732.4 (CD3D):c.128G > A, p.Trp43∗ (variation ClinVar#VCV000643120.1; pathogenic). This variant creates premature stop-gain in CD3D (CD3 antigen, delta subunit, autosomal recessive; MIM#186790), resulting in loss-of-function. He also had "X-linked agammaglobulinemia" (MIM#300755) due to hemizygous missense variant, NM_001287344.1 (BTK):c.80G > A, p.Gly27Asp (novel). He had a sibling who passed away in infancy of unknown disease and family members with autoimmune disorders. Despite these clear clues, he was immunized with BCG at birth and rotavirus at 2 and 4 months. He was well in the first four months. He then developed high-fever, lymphadenopathy, and refractory diarrhea. Stool was positive for rotavirus, and lymph node biopsy showed acid-fast bacilli, consistent with tuberculosis lymphadenitis. These infections were serious and markedly complicated his clinical course, which included bone marrow transplantation from a matched sibling. CONCLUSIONS: These unfortunate events could have been avoided by compiling the available clinical information. This patient underscores the importance of implementing proper policies for BCG and rotavirus vaccinations. International registries of adverse events of universally administered vaccines are crucial.

Genetic variants in children with chronic respiratory diseases.

Founder mutations and autosomal recessive (AR) disorders are common in the Arabian Peninsula due to frequent consanguineous marriages. As a result, the pulmonary service at Tawam Hospital (Al Ain, UAE) routinely requests genetic testing for children with persistent (unexplained) respiratory problems. The main purpose of this report was to underscore the usefulness of these tests. Ten children with severe respiratory diseases due to complex genetic findings are described here. Forty-one variants (six novel) were detected, averaging four per patient (range: 1-9). Seven (17%) variants were homozygous and 34 (83%) heterozygous; some variants were known to show monoallelic expression. Using binomial probability distribution, the fetal-risk for having AR disorder(s) as a function of the number of shared variants by a couple ranged from 0.25 (having one shared variant) to 0.9249 (having nine shared variants). In cultures where increased size of homozygous genomic segments is common, children often have multiple variants that could cause complex clinical phenotypes. Identifying pathogenic variants assists in clinical care, family counseling, and disease prevention through genetic screening.

Idelalisib induces apoptosis in the lymphoid tissues and impairs lung function in mice.

Idelalisib, an inhibitor of the phosphatidylinositol-3-kinase p110δ subunit (PI3Kδ), is approved for treating lymphoid malignancy. The drug is associated with hematopoietic and pulmonary toxicities, which limit its clinical use. However, the toxicity mechanisms are not completely elucidated. In this study, mice were intraperitoneally injected with idelalisib (40 or 80 µg/g) or dimethyl sulfoxide for five days every week for up to four weeks to evaluate the changes in the thymus, spleen, and pulmonary functions. Idelalisib treatment induced thymic involution, decreased CD4+/CD8+ T-cell population, and increased CD4-/CD8- T-cell population. In the spleen, idelalisib dose dependently decreased the lymphocyte viability and cell count. Idelalisib-treated mice exhibited enhanced cleaved caspase-3 expression in the thymus, spleen, and lung tissues. Idelalisib augmented thoracic and airway resistance and decreased thoracic compliance. Thus, PI3Kδ has physiological roles in T-cell development and airway function. Monitoring drug toxicity is important for developing follow-up compounds that target PI3Kδ signalling.

Dyslipidemia, subclinical inflammation, hepatic cholestasis and endothelial dysfunction in schoolchildren with excess fat: A study from the United Arab Emirates.

BACKGROUND: The impact of obesity on cardiovascular health of young children is still to be fully illustrated. This study measured biomarkers for glycemic control, lipid metabolism, systemic inflammation, endothelial dysfunction, and hepatic cholestasis in schoolchildren. Its main purpose was to determine whether metabolic derangements could be detected in young children with excess fat. METHOD: This cross-sectional study involved 967 children in the second, sixth, and tenth grades (median age, 7.3, 11.3, and 15.4 years, respectively). Using the International Obesity Task Force interpretation (IOTF) of body-mass-index (BMI), children were stratified as thin (<5th centiles), normal (5th to <85th centiles), overweight (85th to <95th centiles), obese (95th to <98th centiles), or extremely-obese (≥98th centiles). Waist circumference was also measured. Several metabolic determinations were then used as surrogate biomarkers for cardiovascular risks. RESULTS: Prevalence of BMI≥85th centile among the second graders was 13.1%, sixth graders 42.2%, and tenth graders 33.8%. BMI≥85th centile was associated with a tendency for higher hemoglobin A1c (p≥0.160) and higher blood glucose (p≥0.197). For the second graders, BMI≥85th centile was associated with higher high-sensitivity C-reactive protein (hs-CRP, p<0.001), higher tumor necrosis factor-α (TNF-alpha, p<0.001), higher interleukin-6 (IL-6, p<0.001), higher soluble intercellular cytoadhesive molecule-1 (sICAM-1), higher triglycerides (p≤0.024), and lower high-density lipoprotein (HDL, p<0.001). Additionally, for the sixth and tenth graders, BMI≥85th centile was associated with higher gamma-glutamyl transferase (GGT, p<0.001). In the sixth graders, BMI≥85th centile was insignificantly changed with sICAM-1 or the soluble vascular cytoadhesive molecule-1 (sVCAM-1). CONCLUSIONS: The studied children with excess fat had increased risks for developing systemic inflammation, dyslipidemia, endothelial dysfunction, cholestasis, and diabetes. These results suggest that metabolic biomarkers should be included in the routine assessment of children with an overweight problem.

Nasopharyngeal isolates and their clinical impact on young children with asthma: a pilot study.

INTRODUCTION: Respiratory infections have significant effects on childhood asthma. Viral respiratory infections, such as rhinovirus and respiratory syncytial virus are likely to be important in the development and exacerbation of asthma. In this study, we investigated the nasopharyngeal colonization in children with asthma to determine the prevalence of pathogens and their contribution to respiratory symptoms and airway resistance during winter. METHODS: From December 2016 to March 2017, 50 nasopharyngeal specimens were collected from 18 patients (age, 5.0±1.1 years) with asthma and 9 specimens from 9 control children (age, 4.9±1.0 years). Samples were tested for 19 viruses and 7 bacteria, using multiplex real-time PCR. Respiratory disease markers included the Global Asthma Network Questionnaire, the Common-Cold Questionnaire, the Global Initiative for Asthma assessment of asthma control, and the airway resistance at 5 Hz by forced-oscillation technique. RESULTS: The most commonly isolated organisms in both groups (patients and controls) were Streptococcus pneumoniae, Haemophilus influenzae, and rhinovirus. Most patients had multiple isolates (median, 3.5; range, 1-5), which changed during the study period. Types of isolates were 4 bacteria (S. pneumoniae, H. influenzae, Bordetella pertussis, and Bordetella parapertussis) and 6 viruses (rhinovirus, enterovirus, metapneumovirus, adenovirus, coronaviruses, and parainfluenza viruses). Similar isolates, including influenza A-H3 virus and bocavirus, were detected in the controls. Of the 9 patients with "wheezing disturbing sleep ≥1 per week", 6 had rhinovirus, 2 coronaviruses, and 1 no detectable viruses. Patients with mild common cold symptoms had significantly higher airway resistance at 5 Hz z-score (P=0.025). CONCLUSION: Multiple respiratory pathogens were isolated from many patients with asthma, which appeared to contribute to disease symptoms and airway resistance. Minimizing children's exposure to respiratory pathogens might be beneficial, especially during winter.

Forebrain cellular bioenergetics in neonatal mice.

BACKGROUND: Hypoglycemia occurs frequently in the neonate and may result in neurologic dysfunction. Its impact on the kinetics of cellular respiration and bioenergetics in the neonatal brain remains to be explored. AIMS: Develop murine model to investigate the effects of hypoglycemia on neonatal brain bioenergetics. STUDY DESIGN: Forebrain fragments were excised from euthanized BALB/c pups aged <24 hours to 14 days. We measured cellular respiration (µM O2 min-1.mg-1) in phosphate-buffered saline with and without glucose, using phosphorescence oxygen analyzer, as well as cellular adenosine triphosphate (ATP, nmol.mg-1) using the luciferin-luciferase system. RESULTS: In the presence of glucose, although cellular respiration was 11% lower in pups ≤3 days compared to those 3- 14 days old (0.48 vs. 0.54), that difference was not statistically significant (p = 0.14). Respiration driven by endogenous metabolic fuels (without added glucose) was 16% lower in pups ≤3 days compared to those 3- 14 days (0.35 vs. 0.42, p = 0.03), confirming their increased dependency on exogenous glucose. Although cellular ATP was similar between the two age groups (14.9 vs. 11.2, p = 0.32), the ATP content was more severely depleted without added glucose in the younger pups, especially in the presence of the cytochrome c oxidase inhibitor cyanide. The first-order rate constant of cellular ATP decay (hydrolysis) was 44% lower in 2-day-old pups compared to 14-day-old mice (0.43 vs. 0.77 min-1, p = 0.03). CONCLUSIONS: Forebrain cellular respiration and ATP consumption are lower in young pups than older mice. In the absence of glucose, the support for these processes is reduced in young pups, explaining their brain hypersensitivity to hypoglycemia.

Intrahepatic cholestasis in two omani siblings associated with a novel homozygous ATP8B1 mutation, c.379C>G (p.L127V).

We report two Omani brothers with intrahepatic cholestasis that resolved with supportive care. In one, cholestasis began in infancy; in the other, only at the age of 18 months. Whole exome sequencing identified a novel homozygous variant, c.379C>G (p.L127V) in ATP8B1. Those attending patients with cholestasis from the Arabian peninsula should be aware of this mutation and of the variation in its phenotypic effects.

Psychological Assessment of Emirati Patients Pursuing Bariatric Surgery for Obesity.

BACKGROUND: Obesity is currently a rapidly growing global problem of epidemic proportions and is especially prevalent in economically developed countries such as the United Arab Emirates. Obese individuals are increasingly considering bariatric surgery as their preferred means of choice for the reduction of excess body fat. This study explored the psychological characteristics that may potentially complicate the surgical management of obesity. METHODS: This was a cross-sectional study of Emirati patients attending a bariatric clinic at Tawam Hospital, Al Ain, United Arab Emirates, between December 2010 and February 2012. Participants were assessed using standard clinical psychiatric interviews. Also used were screening instruments such as the Hospital Anxiety and Depression Scale, Sheehan Disability Scale (SDS), Body Image Quality of Life Inventory (BIQLI), and Multidimensional Body-Self Relations Questionnaire-Appearance Scale (MBSRQ-AS). RESULTS: A total of 105 patients, 70% of whom were female, participated in this study. Participants were found to have frequencies of anxiety and depressive symptoms at levels of 24% and 13%, respectively. Participants also reported perceived functional disabilities in the following: work/school (27%), social life (36%), family/home (35%), and religious duties (39%). A total of 13 participants (12%) had BIQLI scores showing slight-to-moderate effects on their quality of life. The mean MBSRQ-AS subscale on self-classified weight was higher than the reported norms. Anxiety and depressive symptoms positively correlated with functional impairment (SDS) and negatively correlated with quality of life (BIQLI) (P = .000). MBSRQ-AS subscales significantly correlated with depression, functional impairment, and quality of life (P ≤ .035). CONCLUSIONS: Anxiety, depression, perceived functional disability, impairment in quality of life, and disturbance of self-image were found to be common among participants in the study pursuing bariatric surgery for obesity. Recognition, assessment, and treatment of these symptoms are expected to be conducive to positive outcomes of bariatric surgery.

Subclinical Inflammation and Endothelial Dysfunction in Young Patients with Diabetes: A Study from United Arab Emirates.

BACKGROUND: The impact of obesity and dyslipidemia on cardiovascular health in adolescents and young adults with diabetes is incompletely understood. This study evaluated the effects of these co-morbidities on markers of inflammation and endothelial dysfunction in young patients with the disease. METHODS: The study investigated sets of inflammatory, endothelial, and adipocyte biomarkers in 79 patients with type 1 diabetes, 55 patients with type 2 diabetes, and 47 controls. RESULTS: Mean (±SD) age was 20±6 y (median = 17, range = 12-31). Patients with diabetes had higher levels of cytoadhesive molecules (sICAM-1 and sVCAM-1, p<0.001), adiponectin (p<0.001), and haptoglobin (p = 0.023). Their heart rate variability assessment revealed lower standard deviation of beat-to-beat intervals and lower total power (p≤0.019), reflecting autonomous nervous dysfunction. Hemoglobin A1c >8.0% (estimated average blood glucose >10 mmol/L) was associated with higher adiponectin (p<0.001) and obesity was associated with lower adiponectin (p<0.001); thus, obesity damped the effect of hyperglycemia on adiponectin. Obesity was associated with higher sICAM-1 (p≤0.015), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP), p<0.001. Similarly, high-density lipoprotein (HDL) <1.02 mmol/L was associated with higher sICAM-1, TNFα, IL-6, and hsCRP (p≤0.009) and lower adiponectin (p<0.001). Adiponectin correlated negatively with the inflammatory biomarkers in patients with diabetes. CONCLUSION: Subclinical inflammation and endothelial dysfunction are common among young patients with diabetes. Poor diabetes control is associated with higher adiponectin. Obesity and dyslipidemia are associated with lower adiponectin and higher inflammatory and endothelial biomarkers. Intuitively, these predictors of cardiovascular disease are amenable to proper glycemic control, nutritional choices, and regular exercise.

Inflammatory markers and cardiovascular risks among overweight-obese Emirati women.

BACKGROUND: The prevalence of abdominal obesity among women in UAE is exceptionally high. However, its impact on cardiovascular health has not been adequately investigated. The aims of this study were to investigate: (1) correlations between inflammatory and oxidative biomarkers vs. anthropometric and metabolic measures; (2) rates of dyslipidemia, diabetes, and hypertension and (3) risks of cardiovascular disease. METHODS: One hundred ten "healthy" overweight/obese Emirati women attending nutrition counselling clinics were randomly recruited. All participants had completed questionnaire, physical examination and laboratory assessment. RESULTS: The participants' mean ± SD of age, body mass-index, waist circumference were 39 ± 9 years, 34 ± 6 kg/m(2) and 100 ± 13 cm respectively. Among the studied women 45 % met diagnostic criteria for metabolic syndrome showing a positive correlation of hsCRP with BMI (p = 0.002), body fat (p = 0.002) and waist circumference (p = 0.018). There was positive correlation of IL-6 with waist circumference (p = 0.019) and adiponectin with HDL (p = 0.007). Prevalence of HDL <1.3 mmol/L or triglycerides ≥1.7 mmol/L were 82 %, dysglycemia 31 %, and hypertension 27 and 37 % of women had either 'high' or 'moderate' calculated cardiovascular 10-year risk score. CONCLUSION: The levels of inflammatory and oxidative stress markers were highly prevalent among overweight/obese Emirati women and this may predispose to increasing cardiovascular risks at relatively young age. Thus effective strategies to impact cardiovascular burden and conducting outcome studies assessing the increased risk of cardiovascular disease and addressing obesity prevention among women are urgently needed.

Bioenergetics of the spinal cord in experimental autoimmune encephalitis of rats.

BACKGROUND: Mitochondrial dysregulation is important in axonal damage and demyelination in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). There is however, no evidence in the literature of any study that has examined cellular bioenergetics of the central nervous system (CNS) during the early development and clinical course of EAE. EAE, a rodent model of relapsing/remitting MS, is a CD4(+) T cell-mediated disease of the CNS. We hypothesize that CNS bioenergetics might predict prognosis, and that preserved bioenergetics might underlie the remission from disease. The study aims therefore, to determine whether the clinical history of EAE is influenced by cellular respiration of the CNS in susceptible Dark Agouti (DA) and resistant Albino Oxford (AO) rats. METHODS: Experimental autoimmune encephalomyelitis was induced by myelin basic protein in complete Freud Adjuvant in the footpads of DA and AO rats. A phosphorescence analyzer that determines cellular respiration was used to monitor oxygen consumption and ATP concentration was measured using the Enliten ATP assay system. Disease pathology was demonstrated by H&E and Luxol fast blue staining of sections of the lumbar regions of the spinal cord. Mitochondrial size in relation to axonal size was determined by electron microscopy. Apoptosis was studied by HPLC measurement of intracellular caspase-3 activity and caspase immunohistochemistry. Role and source of caspase 1 was studied by double immunofluorescence with antibodies for caspase-1, microglia (anti-Iba1) and astrocytes (anti-GFAP). RESULTS: The cellular respiration of the CNS did not vary between diseased and normal rats. We also demonstrate here, that at the peak of disease, inflammation as shown by caspase-1, produced by activated microglia and infiltrating cells, was significant in susceptible DA rats. The mitochondrial:axonal size ratio did not vary in the different groups although mitochondria were smaller in spinal cords of diseased DA rats. Demyelination, observed only in areas of mononuclear infiltration of the spinal cord of diseased DA rats, was demonstrated by light microscopy and electron microscopy. CONCLUSION: We conclude that EAE at this early stage does not significantly affect CNS cellular respiration and this might underlie the reason for the recovery of diseased rats.

In vitro effects of platinum compounds on renal cellular respiration in mice.

BACKGROUND: Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. METHODS: Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 µM platinum drug in the presence and absence of 100 µM N-ethylmaleimide for ≤ 6 h. RESULTS: Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. CONCLUSIONS: These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.