Loss-of-function variant in spermidine/spermine N1-acetyl transferase like 1 (SATL1) gene as an underlying cause of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complicated, lifelong neurodevelopmental disorder affecting verbal and non-verbal communication and social interactions. ASD signs and symptoms appear early in development before the age of 3 years. It is unlikely for a person to acquire autism after a period of normal development. However, we encountered an 8-year-old child who developed ASD later in life although his developmental milestones were normal at the beginning of life. Sequencing the complete coding part of the genome identified a hemizygous nonsense mutation (NM_001367857.2):c.1803C>G; (p.Tyr601Ter) in the gene (SATL1) encoding spermidine/spermine N1-acetyl transferase like 1. Screening an ASD cohort of 28 isolated patients for the SATL1 gene identified another patient with the same variant. Although SATL1 mutations have not been associated with any human diseases, our data suggests that a mutation in SATL1 is the underlying cause of ASD in our cases. In mammals, mutations in spermine synthase (SMS), an enzyme needed for the synthesis of spermidine polyamine, have been reported in a syndromic form of the X-linked mental retardation. Moreover, SATL1 gene expression studies showed a relatively higher expression of SATL1 transcripts in ASD related parts of the brain including the cerebellum, amygdala and frontal cortex. Additionally, spermidine has been characterized in the context of learning and memory and supplementations with spermidine increase neuroprotective effects and decrease age-induced memory impairment. Furthermore, spermidine biosynthesis is required for spontaneous axonal regeneration and prevents α-synuclein neurotoxicity in invertebrate models. Thus, we report, for the first time, that a mutation in the SATL1 gene could be a contributing factor in the development of autistic symptoms in our patients.

Aging-Related Protein Alterations in the Brain.

Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-ß protein precursor (AßPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aß and AßPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.

Computational design of experimentally validated multi-epitopes vaccine against hepatitis E virus: An immunological approach.

Hepatitis E virus (HEV) is one of the leading acute liver infections triggered by viral hepatitis. Patients infected with HEV usually recover and the annual death rate is negligible. Currently, there is no HEV licensed vaccine available globally. This study was carried out to design a multi-epitope HEV peptide-based vaccine by retrieving already experimentally validated epitopes from ViPR database leading to epitope prioritization. Epitopes selected as potential vaccine candidates were non-allergen, immunogenic, soluble, non-toxic and IFN gamma positive. The epitopes were linked together by AAY linkers and the linker EAAAK was used to join adjuvant with epitopes. Toll-like receptor (TLR)-4 agonist was used as an adjuvant to boost efficacy of the vaccine. Furthermore, codon optimization followed by disulfide engineering was performed to analyse the designed vaccine's structural stability. Computational modeling of the immune simulation was done to examine the immune response against the vaccine. The designed vaccine construct was docked with TLR-3 receptor for their interactions and then subjected to molecular dynamic simulations. The vaccine model was examined computationally towards the capability of inducing immune responses which showed the induction of both humoral and cell mediated immunity. Taken together, our study suggests an In-silico designed HEV based multi-epitope peptide-based vaccine (MEPV) that needs to be examined in the wet lab-based data that can help to develop a potential vaccine against HEV.

Role of Thioredoxin System in Regulating Cellular Redox Status in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia and a public health problem. It exhibits significant oxidative stress and redox alterations. The antioxidant enzyme systems defend the cellular environment from oxidative stress. One of the redox systems is the thioredoxin system (TS), which exerts decisive control over the cellular redox environment. We aimed to review the protective effects of TS, which include thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. In the following, we discussed the physiological functioning and the role of the TS in maintaining the cellular redox-homeostasis in the AD-damaged brain. Trx protects the cellular environment from oxidative stress, while TrxR is crucial for the cellular detoxification of reactive oxygen species in the brain. However, TS dysregulation increases the susceptibility to cellular death. The changes in Trx and TrxR levels are significantly associated with AD progression. Though the data from human, animal, and cellular models support the neuroprotective role of TS in the brain of AD patients, the translational potential of these findings to clinical settings is not yet applied. This review summarizes the current knowledge on the emerging role of the TrxR-Trx system in AD.

Transcriptomic and Proteomic Analysis Reveals the Potential Role of RBMS1 in Adipogenesis and Adipocyte Metabolism.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

Novel Adiponectin-Resistin Indices and Ratios Predict Increased Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus.

Objectives: Adiponectin and resistin are adipokines involved in insulin resistance, glucometabolic control and adiposity. There is evidence that hypoadiponectinemia and hyperresistinemia are associated with cardiovascular disease. Whether the ratio of Adiponectin-Resistin (AR) and Insulin Resistance Adiponectin-Resistin (IRAR) indices can be used as non-invasive biomarker of cardiovascular disease needs more attention. Therefore, the aim of this study was to assess the relationships of AR and IRAR indices with adiposity, glucometabolic control and cardiovascular risk incurred by high-sensitivity C-reactive protein (hsCRP) in healthy subjects and patients with Type 2 Diabetes Mellitus. Methods: This observational case control study was conducted in the Department of Physiology and Medicine, King Saud University, Riyadh. A total of 191 (control = 84 and diabetic = 107) subjects were recruited. Body composition was assessed by bioelectrical impendence analyzer (BIA). Fasting blood samples were analyzed for glucose, glycosylated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hsCRP), lipid profile, adiponectin, and resistin levels. The AR and IRAR indices were determined by formulas. Results: Serum adiponectin levels were significantly lower in diabetics compared to control (95.45 ± 39.27 ng/ml vs 146.64 ± 56.36 ng/ml, p < .001) while serum resistin was significantly higher in diabetic when compared to control (2.94 ± 1.30 ng/ml vs 2.40 ± 1.09 ng/ml, p = .003). Furthermore, AR and IRAR indices were significantly increased in diabetic subjects when compared to control (.82 ± .29 vs .48 ± .35, p < .001) and (.30 ± .10 vs .17 ± .12, p < .001) respectively. ROC analysis revealed that these indices predicted increased cardiovascular risk with area under the curve (AUC) for adiponectin = .717 ( p = .001), resistin = .635 ( p = .002), AR index = .740 ( p < .001), and IRAR index = .737 ( p < .001) respectively. AR index correlated positively with Triglycerides (r = .354, p < .01), hsCRP (r = .264, p < .01), HbA1c (r = .425, p < .01), fat mass (r = .164, p < .05), Waist/Hip Ratio (WHR) (r = .248, p < .01), and negatively with high density lipoprotein (r=-.327, p < .01). Furthermore, IRAR index more strongly correlated with Triglycerides (r = .409, p < .01), hsCRP (r = .268, p < .01), HbA1c (r = .508, p < .01), fat mass (r = .152, p < .05), WHR (r = .256, p < .01), and negatively with high density lipoprotein (r = -.340, p < .01). Conclusions: AR and IRAR indices correlate significantly with adiposity, glucometabolic control and cardiovascular risk in type 2 diabetic patients and non-diabetic individuals. They may prove to be useful integrated biomarkers to predict metabolic dysregulation and cardiovascular risk.

Antimicrobial, Antibiofilm, and Antioxidant Potentials of Four Halophytic Plants, Euphorbia chamaesyce, Bassia arabica, Fagonia mollis, and Haloxylon salicornicum, Growing in Qassim Region of Saudi Arabia: Phytochemical Profile and In Vitro and In Silico Bioactivity Investigations.

The current study aimed to investigate the phytochemical contents and antioxidant, antimicrobial, and antibiofilm activities of four halophytic plants, namely, Euphorbia chamaesyce, Bassia arabica, Fagonia mollis, and Haloxylon salicornicum, native to central Saudi Arabia. The alcoholic extract of E. chamaesyce was found to be the most potent in various bioactivities-based evaluations and rich in polyphenols and flavonoid secondary metabolites, with 68.0 mg/g and 39.23 mg/g gallic acid and quercetin equivalents, respectively. Among all plants' extracts, the alcoholic extract of E. chamaesyce had the highest DPPH scavenging and metal chelating antioxidant activities at 74.15 Trolox equivalents and 16.28 EDTA equivalents, respectively. The highest antimicrobial activity of E. chamaesyce extract was found to be against Shigella flexneri, with a mean zone of inhibition diameter of 18.1 ± 0.2 mm, whereas the minimum inhibitory concentration, minimum biocidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration values were 12.5, 25, 25, and 50 mg/mL, respectively. The LC-ESI-MS/MS analysis of the E. chamaesyce extract showed the presence of six flavonoids and ten phenolic constituents. The in silico binding of the E. chamaesyce extract's constituents to Staphylococcus aureus tyrosyl-tRNA synthetase enzyme displayed -6.2 to -10.1 kcal/mol binding energy values, suggesting that these constituents can contribute to the antimicrobial properties of the plant extract, making it an essential medicinal ingredient. In conclusion, these results warrant further investigation to standardize the antimicrobial profiles of these plant extracts.

Relationship of Plasma Gremlin 1 Levels with Body Adiposity and Glycemic Control in Saudi Female Type 2 Diabetes Patients.

Objective: Gremlin 1 is a novel adipokine that plays an important role in obesity and type 2 diabetes mellitus (T2DM). In the current study, we aimed to evaluate plasma levels of Gremlin 1 in diabetic and non-diabetic Saudi adult females and its correlation with body composition, glycemic control and lipid profile. Methods: A case-control study was conducted among 41 T2DM and 31 non-diabetic adult age matched females (controls). All patients underwent body composition by bioelectrical impedance analysis, with a commercially available body analyzer. Fasting venous samples were analyzed for glycemic markers and lipids, while plasma Gremlin 1 was measured by ELISA. The results were compared between the two groups and correlated with other anthropometric and adiposity parameters. Results: Gremlin 1 levels were elevated in T2DM patients (345 ± 26 ng/mL) when compared to control subjects (272 ± 16 ng/mL, p < 0.05). Diabetic patients having poor glycemic control had significantly higher Gremlin 1 levels (382 ± 34 ng/mL) compared to patients with good glycemic control (291 ± 37 ng/mL, p < 0.05). Pearson correlation analysis revealed a positive correlation of Gremlin 1 with fat mass (r = 0.246, p = 0.012), HbA1C (r = 0.262, p = 0.008) and HOMA-IR index (r = 0.321, p = 0.001). Conclusion: Our study demonstrates an important role of Gremlin 1 in glycemic control and body adiposity in the pathophysiology of obesity and T2DM. Gremlin 1 may emerge as a promising biomarker and therapeutic target in obesity and T2DM.

Modification of SWCNTs with hybrid materials ZnO-Ag and ZnO-Au for enhancing bactericidal activity of phagocytic cells against Escherichia coli through NOX2 pathway.

Zinc oxide-silver (ZnO-Ag), and zinc oxide-gold (ZnO-Au) nano-composites were prepared through wet chemical process and laced into single-walled carbon nanotubes (SWCNTs) to yield ZnO-Ag-SWCNTs, and ZnO-Au-SWCNTs hybrids. These nano-composite-laced SWCNTs hybrids were characterized using Raman spectroscopic, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses. The hybrids were evaluated for their effects on phagocytic cells and bactericidal activity against the gram-negative bacteria E. coli. Their phagocytic cell activities and intracellular killing actions were found to be significantly increased, as the ZnO-Ag-SWCNTs and ZnO-Au-SWCNTs nano-hybrids induced widespread clearance of Escherichia coli. An increase in the production of reactive oxygen species (ROS) also led to upregulated phagocytosis, which was determined mechanistically to involve the phagocyte NADPH oxidase (NOX2) pathway. The findings emphasized the roles of ZnO-Ag- and ZnO-Au-decorated SWCNTs in the prevention of bacterial infection by inhibiting biofilm formation, showing the potential to be utilized as catheter coatings in the clinic.

Retardation of Bacterial Biofilm Formation by Coating Urinary Catheters with Metal Nanoparticle-Stabilized Polymers.

Urinary catheter infections remain an issue for many patients and can complicate their health status, especially for individuals who require long-term catheterization. Catheters can be colonized by biofilm-forming bacteria resistant to the administered antibiotics. Therefore, this study aimed to investigate the efficacy of silver nanoparticles (AgNPs) stabilized with different polymeric materials generated via a one-step simple coating technique for their ability to inhibit biofilm formation on urinary catheters. AgNPs were prepared and characterized to confirm their formation and determine their size, charge, morphology, and physical stability. Screening of the antimicrobial activity of nanoparticle formulations and determining minimal inhibitory concentration (MIC) and their cytotoxicity against PC3 cells were performed. Moreover, the antibiofilm activity and efficacy of the AgNPs coated on the urinary catheters under static and flowing conditions were examined against a clinical isolate of Escherichia coli. The results showed that the investigated polymers could form physically stable AgNPs, especially those prepared using polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Preliminary screening and MIC determinations suggested that the AgNPs-EC and AgNPs-PVP had superior antibacterial effects against E. coli. AgNPs-EC and AgNPs-PVP inhibited biofilm formation to 58.2% and 50.8% compared with AgNPs-PEG, silver nitrate solution and control samples. In addition, coating urinary catheters with AgNPs-EC and AgNPs-PVP at concentrations lower than the determined IC50 values significantly (p < 0.05; t-test) inhibited bacterial biofilm formation compared with noncoated catheters under both static and static and flowing conditions using two different types of commercial Foley urinary catheters. The data obtained in this study provide evidence that AgNP-coated EC and PVP could be useful as potential antibacterial and antibiofilm catheter coating agents to prevent the development of urinary tract infections caused by E. coli.

Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant, anti-inflammatory, and antihyperlipidemic properties?

AIMS: Although trastuzumab (TZB)-induced cardiotoxicity is well documented and allicin (one of the main active garlic ingredients) has ameliorating effects against numerous causes of toxicities; however, the influence of allicin on TZB-induced cardiotoxicity has not been investigated yet. Therefore, the current work explored the potential cardioprotective structural, biochemical, and molecular mechanisms of allicin against TZB-induced cardiotoxicity in a rat's model. METHODS: Forty rats were divided into four equal groups and treated for five weeks. The control group (G1) received PBS, the allicin group (G2) received allicin (9 mg/kg/day), the TZB group (G3) received TZB (6 mg/kg/week), and the allicin+TZB group (G4) received 9 mg of allicin/kg/day +6 mg of TZB/kg/week. Heart specimens and blood samples were processed for histopathological, immunohistochemical, biochemical, and molecular investigations to determine the extent of cardiac injury in all groups. KEY FINDINGS: The myocardium of G3 revealed significant increases in the numbers of inflammatory and apoptotic cells and the area percentage of collagen fibers and TNF-α immunoexpression compared with G1 and G2. Besides, qRT-PCR analysis exhibited significant reductions of SOD3, GPX1, and CAT expressions with significant increases in TNFα, IL-1ß, IL-6, cTnI, cTnT, and LDH expressions. Additionally, flow cytometry analysis demonstrated a significant elevation in the apoptotic and ROS levels. In contrast, allicin+TZB cotherapy in G4 ameliorated all previous changes compared with G3. SIGNIFICANCE: The current study proves that allicin could be used as a novel supplementary cardioprotective therapy to avoid TZB-induced cardiotoxicity via its anti-inflammatory, antifibrotic, antioxidant, antihyperlipidemic, and antiapoptotic properties.

Anodal Transcranial Direct Current Stimulation (tDCS) Over the Primary Motor Cortex (M1) Enhances Motor Response Inhibition and Visual Recognition Memory.

BACKGROUND Transcranial direct current stimulation (tDCS) is a non-invasive brain modulatory technique that can boost cognitive processes and alter performance in cognitive tasks. The effect of anodal-tDCS on cognitive functions following a single session has been repeatedly reported. However, results are varied, mixed, and confounded by several factors, including differences in tDCS current intensity and sham conditions used. Therefore, we assessed the effect of a single session of anodal-tDCS over the primary motor cortex (M1) on cognitive functions, particularly response inhibitory control and visual recognition memory, in healthy adults. MATERIAL AND METHODS Thirty healthy male subjects participated in a randomized, double-blind, sham-controlled tDCS study (2 mA, for 20 min). In the sham stimulation, subjects received the same intensity (2 mA, for 30 s, ramped up, then ramped down). We assessed the cognitive functions response inhibitory control and visual recognition memory using the stop signal task (SST) and pattern recognition memory (PRM) task before and after the stimulation. RESULTS There was a statistically significant difference in cognitive function as assessed by the stop signal task go trial (SST) (P=0.019) and SST correct response time on go trials (P=0.04) after real stimulation only. There was no significant effect observed in sham condition. CONCLUSIONS The findings suggest that anodal-tDCS applied over M1 improves inhibitory control and visual recognition memory compared to sham stimulation. Thus, application of anodal-tDCS to the M1, as an integral node in inhibitory motor control, might be a promising adjuvant therapeutic intervention for modulation of motor response inhibition.

Influence of social media on parents' attitudes towards vaccine administration.

Vaccination has had tremendous impact on human health. The tendency to hesitate or delay vaccination has been increasing, which has contributed to outbreaks of vaccine-preventable diseases. This cross-sectional study aimed to investigate the prevalence of childhood vaccine hesitancy and social media misconceptions in vaccine refusal among randomly selected parents from October 2019 through March 2020 in the outpatient clinics of King Khalid University Hospital, Riyadh, Saudi Arabia. The data were collected using a three-part questionnaire: the socio-demographic and economic questions, the Parents' Attitudes about Childhood Vaccines (PACV) survey, and questions concerning social media use. Based on the PACV survey tool, 37 parents (11%) scored a value > 50 and were suggested as hesitant (8% hesitant and 3% very hesitant). Overall, 288 parents (89%) scored < 50, hence deemed to not be hesitant about childhood vaccination. There was no significant association between high educational level or social media exposure with vaccine hesitancy. The most commonly used social media platform was Twitter (40%). In conclusion, we report a low prevalence of vaccine hesitancy about childhood vaccination among parents, with no significant impact of education level or social media on vaccine hesitancy. Further studies are required to replicate these findings in other regions and cities to generalize these observations for Saudi Arabia.

Impact of Gastric Sleeve Surgery on Plasma Retinol Binding Protein 4 and Adipsin Levels in Healthy Male Population.

OBJECTIVES: Bariatric surgery provides most substantial and sustainable weight loss measures in individuals with obesity. Caloric restriction is not only intervention, changes in hormonal secretions are also leading contributory mechanisms to reduce body weight and improve the glycaemic control. The aim of this study was to evaluate the impact of gastric sleeve surgery on plasma retinol binding protein 4 (RBP4) and adipsin levels among Saudi male obese population. METHODS: This prospective study was conducted in the Departments of Physiology and Surgery, College of Medicine, King Saud University. Thirty-three obese (BMI>38.3) male patients age ranged from 25 to 50 years were recruited. RBP4 and adipsin levels were analyzed before and 6-12 months after gastric sleeve surgery by ELISA along with plasma glucose, insulin, HOMA-IR and lipid profile. RESULTS: Circulating RBP4 levels were not significantly changed by bariatric surgery (4382.85±40.35 ng before, and 4393.28±33.13 ng after surgery, p=0.842), neither did adipsin (2949.68±46.86 pg before, and 2917.90±41.90 pg after surgery, p=0.535). Segregation of study participants into two age groups, 25-35 and 35-50 years of age, revealed that before surgery older age group (35-50) had higher RBP4 levels compared to younger group (25-35) (p=0.016). However, after surgery RBP4 levels were decreased in older group but not to a significant level (p=0.174). In younger age group after surgery, there was a near significant increase in RBP4 levels (p=0.052). There were no significant changes in RBP4 levels in both age groups after surgery (p=0.461). For adipsin, there were no significant differences before and after surgery in both age groups. Insulin, BMI and HOMA-IR index were decreased after surgery, however there was no correlation with RBP4 and adipsin levels. CONCLUSIONS: The present study findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in Saudi male obese population after gastric sleeve surgery. However, a decrease in RBP4 levels in older individuals after surgery needs further investigations to understand its effect on weight and glycemic control.

Reference Ranges and Determinant Factors for Fractional Exhaled Nitric Oxide in a Healthy Saudi Adult Population.

BACKGROUND Fractional exhaled nitric oxide (FENO) has emerged as a promising marker in respiratory research. The aim of this study was to determine the reference range values of FENO for healthy Saudi adults and the factors associated with FENO levels. MATERIAL AND METHODS This cross-sectional study was conducted at the Department of Physiology, King Saud University, Riyadh, Saudi Arabia, from January 2016 to August 2017. A total of 429 healthy Saudi adults were initially recruited. The final selection included 412 participants, consisting of 307 men and 105 women. FENO measurements were performed according to the current recommendations of the American Thoracic Society. RESULTS We observed that the FENO levels of women were significantly lower than those of men (18.6 vs. 21.3, P=0.009). In women, the measured FENO ranged from 5.7 ppb to 42 ppb, and in men from 5.0 ppb to 55.0 ppb. The mean FENO level in the entire study population was 20.6, with a range of 5.0 ppb to 55.0 ppb. The difference became non-significant when we calculated the FENO after adjusting for body surface area by different percentile distributions. Multiple linear regression analysis showed that body surface area and weight were significant predictors of FENO levels. CONCLUSIONS In this study, FENO levels were significantly affected by demographic variables. Therefore, it is important to consider the factors influencing FENO values to make a valid clinical interpretation.

Effects of gastric sleeve surgery on the serum levels of GH, IGF-1 and IGF-binding protein 2 in healthy obese patients.

BACKGROUND: Bariatric surgery is an effective treatment for severe obesity. It also ameliorates diabetes independently of weight loss through mechanisms that are not fully understood. In this study, we investigated the levels of GH, IGF-1 and IGF-binding protein 2 (IGFBP-2) after gastric sleeve surgery in healthy obese individuals. METHOD: This study was conducted in 33 obese (BMI > 38.3) healthy male subjects aged 25 to 50 years undergoing sleeve gastrectomy. GH, IGF-1 and IGFBP-2 levels were evaluated by ELISA at baseline and 6-12 months after surgery. Other parameters, such as glucose, BMI, insulin, HOMA-IR and lipid profile, were also investigated. RESULTS: Systemic GH (12.32 vs. 50.97 pg/mL, p < 0.001) and IGFBP-2 levels (51.86 vs. 68.81 pg/mL, p < 0.001) were elevated after bariatric surgery. There was no change in IGF-1 level from before to after surgery. BMI (52.18 vs. 40.11, p = 0.001), insulin (19.35 vs. 8.80 mIU/L, p < 0.001) and HOMA-IR index (6.48 to 2.52, p < 0.001) were reduced after surgery. Lipid profile analysis revealed that total cholesterol (4.26 vs. 5.12 mmol/L, p < 0.001) and high-density lipoprotein (HDL) (0.90 to 1.55 mmol/L, p < 0.001) were increased, while triglycerides were decreased, after surgery (1.62 vs. 1.05 mmol/L p < 0.001). GH, IGF-1, and IGFBP-2 were not correlated with insulin or lipid parameters. CONCLUSIONS: Our study suggests that improved circulating GH and IGFBP-2 levels may mediate the beneficial effects of gastric sleeve surgery in improving insulin sensitivity and reducing insulin demand.

The Role of Ames Dwarfism and Calorie Restriction on Gut Microbiota.

The gut microbiome (GM) represents a large and very complex ecosystem of different microorganisms. There is an extensive interest in the potential role of the GM in different diseases including cancer, diabetes, cardiovascular diseases, and aging. The GM changes over the lifespan and is strongly associated with various age-related diseases. Ames dwarf (df/df) mice are characterized by an extended life- and healthspan, and although these mice are protected from many age-related diseases, their microbiome has not been studied. To determine the role of microbiota on longevity animal models, we investigated the changes in the GM of df/df and normal control (N) mice, by comparing parents before mating and littermate mice at three distinct time points during early life. Furthermore, we studied the effects of a 6-month calorie restriction (CR), the most powerful intervention extending the lifespan. Our data revealed significant changes of the GM composition during early life development, and we detected differences in the abundance of some bacteria between df/df and N mice, already in early life. Overall, the variability of the microbiota by genotype, time-point, and breeding pair showed significant differences. In addition, CR caused significant changes in microbiome according to gastrointestinal (GI) location (distal colon, ileum, and cecum), genotype, and diet. However, the overall impact of the genotype was more prominent than that of the CR. In conclusion, our findings suggest that the gut microbiota plays an important role during postnatal development in long-living df/df mice and CR dietary regimen can significantly modulate the GM.

Effect of wearing cotton towel Ihram and plain Ihram on lung function among Hajj Pilgrims.

OBJECTIVES: Hajj is the world's largest gathering to Makkah, Saudi Arabia. Wearing cotton made Ihram is a basic and an essential component of Hajj. The aim of this study was to investigate the lung functions among Hajj pilgrims who were wearing cotton towel ihram (ihram with fibers) compared to those who were wearing plain cotton ihram (ihram without fibers). METHODS: Ninety male, non-smoker, Hajj pilgrim volunteers with age ranged 20-60 years were selected. Forty five of them wore cotton towel ihram and 45 wore plain ihram. A day before leaving for Hajj and wearing ihram (6th Dhu-al-Hijjah) lung function base line parameters of Hajj pilgrims were determined. Hajj Pilgrims continuously wear ihram from 7-10th Dhu-al-Hijjah. In the afternoon of 10th Dhu-al-Hijjah, after removal of ihram, all parameters were repeated and at the completion of Hajj when all pilgrims return to their homes at Riyadh, all parameters were recorded again. RESULTS: Before wearing Ihram, anthropometric and lung function baseline parameters were recorded, no significant difference was found between the study population. After wearing Ihram on the 7th Dhu-al-Hijjah and its removal on the 10th Dhu-al-Hijjah significant decline in the lung function test parameters was observed among Hajj pilgrims who were wearing cotton towel ihram. Forced Vital Capacity (FVC) 4.30±1.18 vs. 5.03±1.41 (p=0.01); Forced Expiratory Flow 25% (FEF-25%) 4.39±1.94 vs. 5.69±2.84 (p=0.03); Forced Expiratory Flow-50% (FEF-50%) 2.93±1.65 vs. 4.07±2.08 (p=0.01); Forced Expiratory Flow-75% (FEF-75%) 1.02±0.70 vs. 1.66±0.94 (p=0.002) compared to those who were wearing plain ihram. CONCLUSIONS: Lung function test parameters were decreased among the Hajj pilgrims who were wearing cotton towel ihram compared to those who were wearing plain cotton ihram. The pattern of impairment of lung function shows an obstructive peripheral airway lung involvement. It is suggested to conduct further large sample size studies to confirm the present study observations and reach at better conclusions.

Cortical thickness, neurocognitive, and body composition effects of fasting during Ramadan.

BACKGROUND: We aimed to study the anatomical, physiological, and cognitive function of healthy individuals practicing fasting during the month of Ramadan. Measurements were taken 1 week before and 2 weeks after Ramadan fasting. MATERIALS AND METHODS: Twelve healthy male individuals (mean age ± standard error of the mean: 34.3 ± 2.9 years; body mass index: 26.26 ± 1.4 kg/m2) were assessed for various parameters before and after Ramadan fasting. All the tests were performed in the morning. Body composition characteristics were assessed by bioelectrical impedance analysis using a commercially available body composition analyzer. For neurocognitive analysis, participants underwent the stop signal task (SST), pattern recognition memory task (PRM), and spatial working memory strategy (SWM) from the Cambridge Neuropsychological Test Automated Battery. T1-weighted, 1 mm-thick magnetic resonance images were also acquired. RESULTS: Anthropometric analysis showed a significant decrease in body weight, fat-free mass (FFM), trunk FFM, and trunk predicted muscle mass, while the other body composition parameters did not exhibit any changes. The stop signal reaction time (SSRT) latency (ms) (P > 0.05) and PRM did not show any significant difference before and after fasting. SWM task (P < 0.05) improved significantly after fasting. Cortical thickness data of the whole brain were not significantly different after fasting at any brain location. There was a significant correlation between the left amygdala and the SWM strategy (r 2 = 0.518) and between fat and brain segmentation volume (r 2 = 0.375). CONCLUSION: Our pilot data suggest that Ramadan fasting leads to weight loss and FFM reductions and improve cognitive function.

Brain Training Games Enhance Cognitive Function in Healthy Subjects.

BACKGROUND Brain training games (BTG) are believed to play a major role in improving cognitive functions. The current study evaluated if BTG showed positive impact on attention and memory functions compared with baseline visit in healthy subjects. MATERIAL AND METHODS The study was carried out from October 2015 until April 2016 in the Department of Physiology, College of Medicine, King Saud University and in King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. We enrolled 51 normal healthy subjects to use a computerized cognitive training game (Lumosity) for exercises that target a range of cognitive functions, including attention, processing speed, visual memory, and executive functions for about 15 min per day, at least 7 days per week, for 3 weeks. The control (n=21) group did not perform the training. Both groups took the CANTAB test before and 3 weeks after training for various cognitive functions (flexibility, memory, attention, speed, and problem solving). Serum samples were used to study the brain-derived growth factor (BDNF) and apolipoprotein (Apo) E (APOE) levels. RESULTS A significant improvement in Lumosity performance index was observed in the active group compared to the control group by the end of training (p-value 0.001). After the training, a statistically significant difference in most of the CANTAB measures, such as attention-switching task (AST), mean correct latency, AST switching cost, AST mean correct latency (congruent), AST mean correct latency (incongruent), AST mean correct latency (blocks 3 and 5) [non-switching blocks], AST mean correct latency (block 7) [switching block], and MOT mean correct latency (all P=0.000). However, in the control group, significant improvements were not observed. A positive correlation between pattern recognition memory (PRM) and APOE was found and people who had higher ApoE levels had faster response. CONCLUSIONS An improvement in different cognitive domains was noted, including attention and motor speed. However, this study warrants further research to determine the long-term effect on other cognitive functions and in different groups (e.g., elderly vs. adults).