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Exposure of newborns to persistent organic pollutants (POPs) is a public health concern. The objective of this study was to assess the prevalence of POPs in human milk collected from lactating mothers in Lebanon and to investigate the sociodemographic, nutritional, and other lifestyle determinants. Fifty-four breast milk samples were collected as per World Health Organization guidelines. A survey was used to assess the anthropometric and demographic characteristics of participants. Dietary habits were evaluated based on a semiquantitative food frequency questionnaire. Organochlorine pesticides and polychlorinated biphenyls were measured in milk samples with liquid-liquid extraction and gas chromatography. Among the screened POPs, dichlorodiphenyldichloroethylene (DDE) was the only POP detected in breast milk samples and was found in only 17.9% of the samples, with a mean (SD) of 11.6 (5.0) μg/L and a range of 5.7 to 21.4 μg/L. Prepregnancy body mass index and age were positively associated with DDE contamination in breast milk. Women who consumed cereals at least two times per week had detectable DDE contamination in their breast milk. Consumption of potatoes and beans at least once per week was also associated with DDE contamination. Our study is the first to assess the presence of POPs in breast milk in Lebanon. The benefits of breastfeeding compensate for the low prevalence of DDE in the breast milk. Our findings highlight the high need to implement monitoring policies, good agricultural practices, and education programs for breastfeeding mothers.

Background: Hypothyroidism is a common endocrine disorder that is managed by a wide range of physicians. There are no data on the pattern of clinical management of hypothyroidism in the Middle East and Africa (MEA) region. Objectives: We sought to document current practices in the management of primary hypothyroidism in the MEA region and compare these with international recommendations and practices elsewhere. Materials and Methods: A convenience sample of physicians practicing in the MEA in relevant disciplines were invited to take a web-based survey consisting of previously validated multiple-choice questions dealing with investigation and treatment of an index case of overt primary hypothyroidism in general and in three special situations. Results: Out of complete 397 responses, 368 were eligible for inclusion in the analysis. The majority were endocrinologists and internal medicine specialists; 82.2% of them have been in clinical practice for 10 years or more. Overt hypothyroidism would be treated using L-T4 alone by 97.2% of respondents; 1.7% would use a combination of L-T4 and liothyronine (L-T3) therapy. The rate of replacement would be gradual (66.5%), an empiric dose, adjusted to achieve target levels (14.7%); or a calculated full replacement dose (18.5%). A target thyroid-stimulating hormone (TSH) of 2.0–2.9 mU/L was favored in the index case of overt hypothyroidism (by 34.4%) followed by a target of 3.0–3.9 mU/L (by 26.0%) of respondents. However, a target of 4.0–4.9 mU/L was the most commonly selected TSH target for an octogenarian (by 33.5% of respondents). Persistent hypothyroid symptoms despite achieving a target TSH would prompt testing for other causes by 86.9% of respondents, a change to L-T4 plus L-T3 therapy by 5.8%, and an increase in the thyroid hormone dose by 4.6%. Evaluation of persistent symptoms would include measurements of complete blood count (82.4%), complete metabolic panel (68.7%), morning cortisol (65.3%), Vitamin B12 levels (54.5%), and serum T3 levels (27.9%). Subclinical disease with a TSH 7.8 mU/L would be treated without further justification by 9.0% of respondents, or in the presence of positive thyroid peroxidase antibodies (65.3%), hypothyroid symptoms (65.0%), high low-density lipoprotein (51.7%), or a goiter (36.7%). The TSH target for a newly pregnant patient was 2.0–2.4 mU/L for 28.5% of respondents, with 15.8% preferring a TSH target of 1.5–1.9 mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 62.9% and every 8 weeks by an additional 17.6%. A hypothyroid patient with a TSH of 0.5 mU/L who becomes pregnant would receive an immediate L-T4 dose increase by only 28.5% of respondents. Conclusions: The survey revealed that (1) nearly exclusive preference for L-T4 alone for therapy, (2) use of age-specific TSH targets for replacement therapy, (3) a low threshold for treating mild thyroid failure, (4) complacent and variable attention to TSH targets in the pregnant and prepregnant woman, and (5) a highly variable approach to both the rate and means of restoring euthyroid status for overt disease. Both alignments with and divergence from guidelines were detected. The results should help in directing focused educational activities in the region, providing a baseline for future monitoring of practices.

Valproic acid (VPA) is a powerful antiepileptic drug that was associated with several neurological and hepatic problems especially with increasing its dose and duration. These problems may be metabolic in origin and related to glucose homeostasis. So, the present study investigated the effect of different doses and durations of VPA on the expression of glucose transporters (Glut1 and Glut4), oxidative stress and inflammatory cytokine (IL-6) in the liver and specific brain regions. Seventy-two male Sprague-Dawley rats were randomly allocated into three equal groups: (1) saline group, (2) 200 mg VPA group and (3) 400 mg VPA group. By the end of experiments, the expressions of Glut1, Glut4 nuclear factor erythroid-like 2 related factor (Nrf2), IL-6 and oxidative stress markers [malondialdehyde (MDA) and glutathione (GSH)] in the liver, corpus striatum, prefrontal cortex (PFC) and cerebellum were assessed. We found that administration of VPA (200 mg and 400 mg) caused a significant decrease in the Glut1 and Glut4 expression in different tissues in a dose- and time-dependent manner (P < 0.01). Also, VPA (200 and 400 mg) caused a significant increase in MDA with a decrease in GSH in tissues at different times. Moreover, VPA (200 and 400 mg) caused significant upregulation in IL-6 expression and downregulation in Nrf2 expression (P < 0.01). The results suggest that increasing the dose and time of VPA therapy downregulates Glut1 and Glut4 in the liver and brain which may impair glucose uptake in these tissues. This effect was associated with enhanced oxidative stress, downregulation of nrf2 and upregulation of IL-6 in liver and brain tissues.

Background Robotic-assisted total knee arthroplasty (TKA) is a growing technique in adult reconstruction. The variations between robotic-assisted and conventional TKA could lead to changes in immediate postoperative outcomes. We aimed to evaluate for differences in postoperative pain, discharge day, as well as post-hospital disposition (home vs subacute rehabilitation facility [SAR]) between robotic-assisted and conventional TKA. Methods We retrospectively identified 2 cohorts of patients who underwent either conventional or robotic-assisted TKA between January 2019 and July 2019. Their average pain scores from postoperative day 0, day 1, and day 2 were recorded. Their postoperative discharge day was recorded, as well as their disposition to either home or a SAR. Preoperatively, all patients are offered robotic-assisted TKA, and only those who want the procedure and undergo a preoperative CT scan receive the robotic-assisted surgery. Statistical analysis was conducted using SPSS. Results One hundred sixty-six patients were identified with 83 in each cohort. No differences between age, race, and gender were found. Despite minor variations in pain levels, the overall postoperative pain score analysis did not strongly favor one technique over the other. The robotic-assisted group had a significantly higher amount of patients discharged to home instead of a SAR and also had a shorter time to discharge than the conventional group. Conclusions Robotic-assisted TKA has similar postoperative pain scores compared with conventional TKA. The robotic-assisted cohort demonstrated other benefits including earlier discharge and are more likely to be discharged home instead of a SAR.

Introduction: Appropriate dose adjustments of glucocorticoids replacement therapy for adrenal insufficiency (AI) is vital. Objective: We sought to scope physicians’ perceptions, and practices regarding Ramadan fasting (RF) impact on the management of AI. Methods: A web-based survey of a convenience sample of endocrinologists. Results: Nearly two-thirds of 145 respondents (64.1%) were adult endocrinologists and almost half (49%) saw more than 10 hypoadrenal patients per year. Most respondents (78.6%) prescribed hydrocortisone, while the minority prescribed other preparations. The glucocorticoid doses were reportedly divided twice daily by 70.8% and thrice daily by 22.2% of respondents. Respondents recognized RF as having potential consequences in adrenal insufficiency patients included causing hypoglycaemia, undue tiredness, and fatigue, hypotension, feeling dizzy, and light-headedness. Symptoms of under-replacement were thought to happen in the late afternoon by 59.3% of respondents. Almost half (45.5%) of respondents thought that RF has some probable or definite impact on glucocorticoid therapy that certainly warrants specific concern and possible action. Three quarters (76.4%) of respondents confirmed providing specific management recommendations during RF. The most frequently reported recommendation was taking in the usual morning dose of hydrocortisone just before pre-dawn meal (Suhor) (57.8%). A third switch patients from hydrocortisone to prednisolone/prednisone. Half reported providing patients with specific recommendations regarding breaking their fast and/or seeking help if hypoadrenal symptoms occur. Conclusions: There is a remarkable variation in the physicians’ perceptions and practices regarding the management of AI during Ramadan. This warrants professional effort to increase the awareness and dissemination of evidence-based guidelines.

Background and Aim: Brucellosis is a zoonotic disease caused by the bacterium of the genus Brucella. This disease is present worldwide, especially in developing and underdeveloped countries, where it is endemic. This first-of-its-kind study in Lebanon aimed to assess the prevalence of brucellosis across the country and to determine the efficacy of a vaccine for reducing losses in herds so that its toll on public health is reduced. Materials and Methods: Three hundred and fifty-three blood serum and 261 milk samples were obtained from cows in different areas of Lebanon. The samples were analyzed using serological tests (rose Bengal, milk ring, and indirect enzyme-linked immunosorbent assay [ELISA]) and confirmed with competitive ELISA and polymerase chain reaction. Results: The highest rate of Brucellae was found in the Bekaa region (10%). After vaccination of 5 cows and 13 heifers at different times, the results showed that all the vaccinated animals have developed an immune response to brucellosis 60 days after vaccination. This vaccine can be considered as stable and preventative to protect against brucellosis in animals and thus protect the public from this infection. Conclusion: These findings will provide further insight into designing future targeted awareness interventions and adapted policies as efforts toward reducing the prevalence and prevention of brucellosis in cattle in Lebanon.

Background: Male hypogonadism is characterized by androgen deficiency in the body. Several studies have shown that testosterone deficiency is inducing a metabolic syndrome and insulin resistance. Although of the unwanted effects of exogenous testosterone replacement therapy, it is the main treatment of male hypogonadism. One of the safe treatment options is Dehydroepiandrosterone (DHEA) replacement therapy which is the precursor of testosterone. Up to date and to the best of our knowledge, no one investigates the effect of DHEA on glucose-6-phosphatase enzyme in a rat model of male hypogonadism and its impact on the metabolic dys-function. Aim of Study: The aim of the research is to investigate the possible protective effect of DHEA on hepatic and meta-bolic dysfunction in a rate model of male hypogonadism through examining its effect on glucose-6-phosphatase enzyme. Moreover, it studies the possible therapeutic effects of the male androgen (DHEA) on the hepatic steatosis and insulin resistance triggered by testosterone deficiency. Material and Methods: Thirty-two Wistar Kyoto rats were divided into 4 groups as follows (I) Untreated controls, (II) Untreated orchidectomized, (III) Control, treated with DHEA and (IV) Orchidectomized, treated with DHEA. Treatment was carried three times per week for 12 weeks. Cobas c111, Roche diagnostic, USA machine was used to measure the level of the glucose, liver enzymes and lipid profile. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure the plasma level of testosterone hormone, insulin and glucose-6-phosphatase enzyme. Results: As expected, the plasma testosterone decreased significantly in ORCH rats, with significant increase in glucose, lipid profile as well as significant decrease in insulin as compared to control rats. Moreover, our data revealed insig-nificant increases in plasma testosterone in ORCH + DHEA with significant increase in ORCH + DHEA compared to control + DHEA. DHEA did not significantly affect G-6-Pase enzyme. Also, ORCH shows significant increase in triglyceride and cholesterol as well as the ORCH + DHEA.Conclusion: Testosterone deficiency and DHEA replace-ment therapy have no effects on glucose 6-phosphatase enzyme. Male hypogonadism is a risk factor for metabolic syndrome and NAFLD that could not be treated effectively with DHEA.

It is important to study the incidence and causes of readmissions in order to understand why they occur and how to reduce them. This study looks at a national sample of patients following total knee arthroplasty (TKA) to identify incidences, trends, causes, and timing of 30-day readmissions.Patients undergoing primary TKA from 2012 to 2016 in the American College of Surgeons National Surgical Quality Improvement Program database were identified (n = 197,192). Patients with fractures (n = 177), nonelective surgery (n = 2234), bilateral TKA (n = 5483), and cases with unknown readmission status (n = 1047) were excluded, leaving a total of 188,251 cases. Linear regression analysis was used to determine trends over time.The incidence of overall 30-day readmission following primary TKA from 2012 to 2016 was 3.19% (6014/188,251), with significant decreases in readmission rates during this time (β = -0.001, P.001). The top 5 causes of readmission included superficial surgical site infection (SSI; 9.7%), non-SSI infection (9.5%), cardiovascular complications (CV; 9.3%), gastrointestinal complications (8.8%), and venous thromboembolisms (8.8%). The most common cause of readmission during postoperative week 1 was CV complications (12.2%), week 2 was superficial SSI (11.6%), week 3 was deep SSI (11.4%), and week 4 was deep SSI (12.4%).Overall, 30-day readmissions following TKA were found to significantly decline from 2012 to 2016. The most common causes of overall readmission included superficial SSI, non-SSI infection, CV complications, gastrointestinal complications, and venous thromboembolisms. However, the most common causes of readmission changed from week to week postoperatively. This data may help institutions develop policies to prevent unplanned readmissions following TKA.

Background Clostridium difficile–associated diarrhea (CDAD) is associated with adverse events and financial liability. As institutions continue to adopt CDAD rates as a quality control metric, it is important to identify patients at risk before surgery, including revision total knee arthroplasty (rTKA). This study was conducted to (1) determine the incidence of CDAD within 30 days of rTKA and (2) identify perioperative risk factors for CDAD following rTKA. Methods The American College of Surgeons National Surgical Quality Improvement Program was queried to identify 6023 rTKA procedures from 2015-2016. Preoperative and perioperative variables, including patient demographics, lab values, comorbidities, operative time, procedure type, presence of postoperative infections, and rates of CDAD were collected. Chi-square and Fisher’s exact tests were used to detect differences between categorical variables, and t-tests were used to compare continuous variables. A stepwise logistic regression model was used to identify the risk factors for CDAD. Results The rate of CDAD within 30 days of rTKA was found to be 0.4% (24/6024). The CDAD rate following aseptic revision was 0.2% (12/4893), while the incidence of CDAD after septic revision was 1.1% (12/1130). Preoperative functional dependence (odds ratio [OR] = 5.14; P = .002), septic revision (OR = 2.77; P = .026), and cancer (OR = 14.26; P = .016) were statistically significant independent risk factors for CDAD after rTKA. Conclusion The incidence of CDAD after rTKA is approximately 0.4% in the United States. Independent risk factors for CDAD include septic revision, preoperative functional dependence, and cancer. Prevention of CDAD in these higher risk patients must be considered before surgery and antibiotic selection for other infections should be managed judiciously.

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg−1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1β, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.

In most of the world, wheat is one of the main staple foods, and is also widely used in livestock feed. In the current study, we investigated the effects of wheat grain consumption on the rat behavior and neurogenesis markers. Thirty male rats were divided into three equal groups (n = 10). Group 1 was the control group fed with chow diet (Carbohydrates 63%, fat 13% and protein 24%), the Group 2 rats were fed with whole grains and the Group 3 rats were fed with refined grains. After 12 weeks, we measured the hippocampal and prefrontal cortical brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), 5-hydroxytryptamine, dopamine, norepinephrine, malondialdehyde (MDA) and reduced glutathione (GSH) levels. Also, we evaluated the rat behavior by forced swimming test (FST) and elevated plus maze (EPM) test. Additionally, we measured serum level of glucose, lipid profile, insulin and cortisol. Weight gain at the end of the study was measured in each group. The rats on a diet of whole and refined grains had low BDNF, NT-3, norepinephrine, dopamine and serotonin significantly (p < .01) in both the hippocampus and prefrontal cortex as compared to control rats. Moreover, the MDA increased significantly with significant reduction in GSH versus the control rats. Moreover, in response to grain consumption, the performance in FST showed a significant (p < .01) shortage in the latency of the attempts to escape as well as a significant prolongation (p < .01) in behavioral immobility as compared to control rats with significant (p < .05) prolongation in time spent in closed arm in EPM. An exclusive diet of either whole or refined grain in a rat model induced anxiety and depressive behaviors and negatively affected the BDNF and NT-3 and modulated the level of the neurotransmitters with significant shift in their behavior. PRACTICAL APPLICATIONS: Grains are considered the major caloric source all over the world that may predispose to the development of chronic diseases. In this research, we evaluated the role of grains in modulating the rate of production of neurogenic factors in rats.

Systemic Lupus erythematosus (SLE) is a chronic multisystem, multifactorial inflammatory autoimmune disease. The SLE patients have 3 times increased risk of mortality based on international data with ethnicity playing an important impact on patients’ morbidity and mortality. Descriptive studies from Saudi Arabia showed variation in clinical features from one region to another. Moreover, reliable inference from these studies is limited by study methodology and lack of translational data using biological samples to understand clinical phenotypes of Saudi SLE patients. The aim of this report is to describe the prospective study protocol of the National Systemic Lupus Erythematosus Cohort in Saudi Arabia. The purpose of this cohort study is multifold: first, to examine clinical characteristics and molecular phenotypes of Saudi SLE patients in relation to local environment and practices/lifestyles; second, to assess long-term outcomes of SLE in Saudi population and factors that influence favorable outcomes; third, to compare the effectiveness of various treatment regimens in Saudi SLE population. This study is a longitudinal prospective cohort study of adult, Saudi SLE patients using open cohort study design. Primary outcomes include disease-related outcomes (activity, improvement, and organ damage) and patient-reported outcomes (quality of life). Secondary outcomes include physiological and molecular modifications associated with changes in disease activity states.Results and analysis are in on-going study. This study provides a source of reliable data for clinical and translational research. This will allow us to have a holistic approach to SLE pathogenesis especially in Saudi population and may take us a step further toward much more personalized medicine. This protocol has been registered in NIH ClinicalTrial.gov (ClinicalTrial.gov identifier: NCT04604990) on October 27, 2020.

Objectives: The present study examined the effect DHEA (dehydroepiandrosterone) on bone mineral content (BMC) and bone mineral density (BMD) and biomarkers of bone remodeling in orchidectomized male rats. Material and Methods: A total of 32 male rats were divided equally into four groups (n = 8): (i) control group (C), (ii) control treated with DHEA (Control + DHEA), (iii) orchidectomized (ORCH) group that underwent bilateral orchidectomy and (iv) orchidectomized (ORCH) rats treated with DHEA (ORCH+DHEA). DHEA treatment started 4 weeks after orchidectomy and continued for 12 weeks. After 12 weeks the bone mineral density (BMD) and bone mineral content (BMC) were assayed in the tibia and femur of the right hind limb of each rat. We also measured the serum levels of the bone turnover markers deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTx), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRAP-5b) and osteocalcin (OC) as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG). Results: Orchidectomy in rats caused significant reduction in BMD, BMC, serum levels of testosterone, PTH (parathyroid hormone), OPG, OC and ALP with significant rise in serum levels of TRAP-5B, RANK, Dpd and NTx1 (p &lt, 0.05). On the other hand, DHEA therapy for 12 weeks caused significant improvement in all studied parameters except NTx1 (p &lt, 0.05). Conclusions: DHEA corrected hypogonadism-induced osteoporosis in male rats probably via inhibiting osteoclastogenesis, stimulating the activity of osteoblasts and stimulating the secretion of PTH and testosterone.

Objectives: “Al Ghodad Al- Somm” is an old Arabic translation for the field of Endocrinology which doesn’t accurately reflect the Greek terminology “Endocrine”, and doesn’t fully describe this science of the glands that secrete hormones and their disorders. Our objectives were to seek the opinion of Arab physicians (Endocrinologists and other physicians) about the accuracy and applicability of the Arabic translation and to suggest a better descriptive and reflective name for the specialty. Methods: An electronic survey of various Arab physicians from the Gulf, Fertile Crescent and North Africa. Results: Responses of 383 out of 400 participants were valid for analysis. The survey results showed that (49%) of participating endocrinologists and (34%) of physicians from other specialties expressed that a more accurate Arabic translation is needed. Conclusions: Practicing Arab physicians expressed the opinion that the Arabic translation “Al- Somm” is deficient and a more accurate term is needed to better reflect our current knowledge of this science of the glands that secrete hormones and their disorders. “The science of hormonal glands, diabetes and metabolism" has been proposed as a term that may better serve this purpose.

Background: The aim of our study was to assess the knowledge, practices, and attitudes towards food allergens and allergies among diagnosed food allergic individuals in Lebanon. Methods: Seventy diagnosed participants were recruited after reaching out to all the allergists of the country. They completed in person or over the phone a comprehensive valid questionnaire composed of 49 questions. Results: Wheat was reported as top food allergen (15.7%), while itchy skin and rash were the most reported symptoms (71.4% and 68.6%, respectively). Only 34 (48.6%) of participants indicated they carry medications, 58 (70.7%) were diagnosed using blood test, and 22 (31.4%) stated that they are very knowledgeable on the topic. In terms of knowledge, participants scored on average 84.2 ± 11.5%. In terms of best practices, participants scored on average 47.8 ± 28.3%. Having a health related educational background increased significantly (p

AIM: The dynamics of coronavirus disease 2019 (COVID-19) pandemic has become of special concern to the rheumatology community. Rheumatic patients are required to engage in effective health management but their behavior is often influenced by intrinsic and extrinsic factors. This cross-sectional study aims to examine patients' experiences during the current pandemic and its implication on their health perception and behavior. METHOD: A patient-centered electronic survey was used, randomly sampling rheumatic patients in Saudi Arabia during March and April 2020. Questions included patients' socio-demographics, diseases, medications, COVID-19 knowledge, source of information, fear level, disease activity perception, health care utilization, medication accessibility, and therapeutic compliance (measured using a modified version of Medication Adherence Reporting Scale). Correlation and regression coefficients were used to evaluate associations among the aforementioned variables. RESULTS: A total of 637 respondents were included. The majority were rheumatoid arthritis patients (42.7%). Patients' knowledge about COVID-19 was correlated with social media use (P = .012). Fear of COVID-19 infection correlated with healthcare facility for follow-up visits (P = .024) and fear of disease deterioration if contracting the infection correlated with patients' levels of knowledge (P = .035). Both types of fear did not correlate with patients' perceptions of disease activity. However, patients' perceptions of worsened disease activity were correlated with unplanned healthcare visits (P < .001), medication non-adherence, and difficulty accessing medication (P = .010 and .006, respectively). CONCLUSION: The COVID-19 pandemic and surrounding public health measures could affect rheumatic patients' health management which might contribute to disease flare-up and subsequently taxing healthcare systems even further.

Antiphospholipid syndrome is a organized autoimmune disease presented with vascular thrombosis and pregnancy morbidity. The Sapporo classification criteria of APS were revised in 2006 and are used as the main diagnosis guideline, which validity as standard measurements is still in debate. This study observe the clinical and laboratory indices of APS among Saudi patients. This is a retrospective study hospital-based population. The clinical and Laboratory manifestations of diagnosed APS patients from electronical medical records identifies by ICD-9 code 795.79 in the King Saud University Medical City, Riyadh, Saudi Arabia, between 1990 and 2012. We selected patients with ICD-9 code 795.79 as. Sapporo criteria applied to all patients, then divided into cases fulfilled criteria and cases failed the criteria. To notice the difference in clinical and laboratory indices and comorbidities between the two groups, the T-test was performed and Logistic regression for the fulfilled criteria and clinical indices of vascular thrombosis, DVT/PE, recurrent, and pregnancy morbidity. A total of 72 (90%) females and 8 (10%) males, with the female-to-male ratio 9:1. The mean (±SD) age at diagnosis was 28.1 (±8.7) years (range 11–63 years). There were 22 patients (27.5%) attained the revised criteria (APS confirmed) and no significant difference between the two groups was observed (p > 0.2). However, we found Sapporo confirmed APS cases had significantly higher percentage of serological manifestation presence than clinically diagnosed APS cases. Though there is no statistically significance, Sapporo confirmed APS cases had advanced odds of undergoing vascular thrombosis (OR = 1.61, 95%CI) and DVT/PE (OR = 1.53, 95%CI) and lesser odds of undergoing recurrent DVT/PE (OR = 0.67, 95%CI) and pregnancy morbidity (OR = 0.63, 95%CI) than the clinically diagnosed APS cases. Over 70% of the study population with diagnosed APS did not accomplish the revised Sapporo criteria due to negative laboratory manifestations, which reflects heterogeneous but not degreed disease severity profiles.

The aim of this study was to investigate the effect of melatonin on oxidative stress and senescence marker protein-30 (SMP30) as well as osteopontin (OPN) expression in the hippocampus of rats subjected to vascular dementia (VD). A total of 72 male rats were divided into six groups (n = 12 each) as follows: (i) untreated control (CON), (ii) sham-operated group, (iii) sham-operated + melatonin, (iv) rats exposed to VD induced by permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (v) rats exposed to VD + melatonin, and (vi) rats exposed to VD + donepezil (DON). At the end of experiment, the hippocampal levels of acetylcholine (ACh), norepinephrine (NE), and dopamine (Dop) were measured. Expression of OPN was determined using immunohistochemistry, and SMP30 expression was determined using real-time PCR in the hippocampus. Hippocampal thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were evaluated. The BCCAO group showed significantly decreased TAC (p p

The aim of this study is to investigate the effect of vanadium and/or insulin on the proinflammatory biomarkers in type 2 diabetes mellitus (T2DM) rat model. Sixty male Sprague Dawley rats were divided into six groups (n = 10). Control group, control vanadium group, T2DM group, insulin-treated diabetic group, vanadium-treated diabetic group, and concomitant insulin and vanadium-treated diabetic group. At the end of the experiment, serum glucose, insulin, lipid profile, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), high sensitivity C reactive protein (hs- CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and adiponectin were measured. Administration of insulin and/or vanadium significantly decreased in the plasma levels of glucose, lipid profile, TNF-α, IL-6, hs-CRP, ICAM-1, and VCAM-1 with significant increase in adiponectin in comparison to the diabetic group. Concomitant administration of insulin and vanadium significantly improved the above measured parameters compared to either insulin or vanadium treatment. Based on our results we can conclude that administration of both vanadium and insulin reduced the low-grade systemic inflammation in T2DM, through reduction of both proinflammatory cytokines and adhesion molecules and increase adiponectin.

BACKGROUND We sought to determine whether swim exercise can inhibit high carbohydrate and fat diet (HCFD)-induced biomarkers of coagulation and thrombosis. MATERIAL AND METHODS Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks. Swim exercise-'treated' rats started swim exercise training from the 11th week until being sacrificed, on Week 15. RESULTS HCFD caused a significant increase in blood glucose, insulin resistance (HOMA-IR), lipidemia, and inflammatory biomarkers. In addition, HCFD significantly modulated coagulation and thrombosis biomarkers; fibrinogen, plasminogen activator inhibitor-1, von Willebrand factor, prothrombin time, activated partial thromboplastin time, blood clotting and bleeding time, and ADP-induced platelet aggregation that was effectively inhibited by swimming exercises. CONCLUSIONS We demonstrate that in an animal model of obesity and insulin resistance, there is a significant change in hemostasis, which is ameliorated by swim exercise.

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 11

Background and aims Chronic diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are associated with chronic inflammation. However, controversial reports as to the key cytokines involved in the process of chronic inflammation hinder development of targeted therapies for patients. This is because, chronic inflammatory process cannot be fully understood by studying the mechanisms of the disease in a short-term or isolated fashion. Understanding of the trend of inflammatory cytokines through longitudinal studies could provide a profound insight into the process of disease progression. Methods We performed a longitudinal analysis of inflammatory cytokines/chemokines and faecal microbiome dysbiosis associated with the diet-induced progression of NAFLD to HCC in diet-induced animal model of NAFLD comparing males and females, since males show a higher incidence of these diseases than females do. Results Longitudinal analyses revealed that a transient and timely increase in LIF and TMIP1 was associated with the inhibition of the progression of NAFLD to HCC in females. On the other hand, chronically increasing trends in CCL12, CCL17, CXCL9 and LIX/CXCL5 were associated with the promotion of the progression of NAFLD to HCC in males. Conclusions We provided empirical evidence that a methodological shift from snapshot observations to longitudinal data collection and analysis can provide a better understanding of chronic liver diseases.

Pharmacogenomic testing, together with early detection of drug-drug interactions, drug-gene interactions, and drug-drug-gene interactions prior to initiating pain management, can improve the selection of optimal opioid medication, and can reduce adverse drug interactions and therapeutic failures.The

Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals.

Type 2 diabetes mellitus (T2DM) is known to be associated with an increased risk of dementia, specifically Alzheimer’s disease and vascular dementia. Intermittent fasting (IF) has been proposed to produce neuroprotective effects through the activation of several signaling pathways. In this study, we investigated the effect of IF on rat behavior in type 2 diabetic rats. Forty male Wistar Kyoto rats were divided into four groups (n = 10 for each): the ad libitum (Ad) group, the intermittent fasting group (IF), the streptozotocin-induced diabetic 2 group (T2DM) fed a high-fat diet for 4 weeks followed by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) 25 mg.kg−1, and the diabetic group with intermittent fasting (T2DM+IF). We evaluated the impact of 3 months of IF (16 h of food deprivation daily) on the levels of brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), serotonin, dopamine, and glutamate in the hippocampus, and rat behavior was assessed by the forced swim test and elevated plus maze. IF for 12 weeks significantly increased (p &lt, 0.05) the levels of NT3 and BDNF in both control and T2DM rats. Additionally, it increased serotonin, dopamine, and glutamic acid in diabetic rats. Moreover, IF modulated glucose homeostasis parameters, with a significant decrease (p &lt, 0.05) in insulin resistance and downregulation of serum corticosterone level. Interestingly, T2DM rats showed a significant increase in anxiety and depression behaviors, which were ameliorated by IF. These findings suggest that IF could produce a potentially protective effect by increasing the levels of BDNF and NT3 in both control and T2DM rats. IF could be considered as an additional therapy for depression, anxiety, and neurodegenerative diseases.

The human ear is most sensitive. Hearing problems increases with age as well as sound pollution. In today’s life, due to noise pollution or some reasons, per year, many people undergo from the problem of tentative hearing loss. In this experiment, 16 patients of different ages were taken, ranging from 20 years to 55 years of both sexes and we studied hearing sensitivity and it was compared between the right and left ears of each patient, as well as the comparability of hearing for different ages taken in this research.

As the population ages, the need for total hip arthroplasty (THA) will increase. However, this will be associated with an increase in comorbidities and a decrease in the ability to independently perform activities of daily living (ADLs). This study was designed to evaluate the impact preoperative functional status has on short-term outcomes after THA.Primary THAs performed from 2012 to 2016 were identified in the National Surgical Quality Improvement Program database. Final analysis included 115,590 cases. Patients who could perform all ADLs were classified as independent functional status (n = 113,436), and patients requiring assistance with ADLs were classified as dependent functional status (n = 2154). Univariate analysis was used to compare perioperative outcomes and 30-day complication rates. Multivariate regression was then applied to determine if preoperative dependent functional status was an independent risk factor for adverse outcomes.Functionally dependent patients were more likely to experience operative times120 minutes (odds ratio [OR] = 1.39; P.001), hospital stays10 days (OR = 2.96; P.001), and nonhome discharge (OR = 2.53; P.001). Dependent functional status was also an independent risk factor for mortality (OR = 3.00; P = .001), reoperation (OR = 1.39; P = .015), readmission (OR = 1.75; P.001), superficial surgical site infection (OR = 1.96; P = .002), wound dehiscence (OR = 2.72; P = .034), pneumonia (OR = 2.16; P = .001), reintubation (OR = 2.31; P = .007), prolonged ventilator use (OR = 3.01; P = .009), renal failure necessitating dialysis (OR = 3.94; P = .002), urinary tract infection (OR = 1.78; P = .001), blood transfusion (OR = 1.75; P.001), and sepsis (OR = 2.38; P = .001).Functionally dependent patients undergoing THA are at higher risk of mortality, adverse perioperative outcomes, and complications. These data may aid for patient counseling and risk stratification.

Diabesity (diabetes associated with obesity) is a major global and local public health concern, which has almost reached an epidemic order of magnitude in the countries of the Arabian Gulf and worldwide. We sought to review the lifestyle trends in this region and to highlight the challenges and opportunities that health care professionals face and attempt to address and correct them. In this regard, we aimed to review the regional data and widely held expert opinions in the Arabian Gulf and provide a thematic review of the size of the problem of diabesity and its risk factors, challenges, and opportunities. We also wished to delineate the barriers to health promotion, disease prevention, and identify social customs contributing to these challenges. Lastly, we wished to address specific problems with particular relevance to the region such as minimal exercise and unhealthy nutrition, concerns during pregnancy, the subject of childhood obesity, the impact of Ramadan fasting, and the expanding role of bariatric surgery. Finally, general recommendations for prevention, evidence-based, and culturally competent management strategies are presented to be considered at the levels of the individual, community, and policymakers.

This study examined the effects of aliskiren (Ali) (direct renin inhibitor) on serum cardiac enzymes (LDH and CK-MB), electrocardiography (ECG) changes, myocardial oxidative stress markers (MDA, CAT, and GSH) and the expression of Bcl2, HO-1, and Nrf2 genes in isoproterenol (ISO)-induced myocardial infarction (MI). A total of 40 male albino rats were allocated into four groups, (1) normal control (NC) group, (2) Ali group (rats received Ali at 10 mg/kg/day p.o. for 5 days), (3) ISO group (rats received ISO 150 mg/kg i.p. for two consecutive days at 24 h intervals), and (4) Ali + ISO group (rats received ISO + Ali at 10 mg/kg/day p.o. for 5 days from the 2nd dose of ISO). ISO group showed significant rise in serum cardiac enzymes (CK-MB and LDH), myocardial damage scores, myocardial MDA, HO-1, myocardial Nrf2 expression with significant reduction in myocardial antioxidants (CAT and GSH), and Bcl2 expression compared to the normal group (p

Objectives: To develop and test the psychometric properties of an Arabic version of Fatigue Severity Scale (FSS-Ar) that can be used to measure fatigue in Arabic patients with disorders where fatigue is a major symptom. Methods: Forward and backward translations of FSS were undertaken to develop an Arabic version. The validity and reliability of the FSS-Ar was then tested on 28 patients with systemic lupus erythematosus (SLE), 24 patients with multiple sclerosis (MS), and 31 healthy subjects. Exploratory factor analysis and hypothesis testing methods were used to examine construct validity. The correlation between FSS-Ar and the vitality domain of the RAND 36-Item Health was examined to test construct validity. The study was conducted at the King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between February and June 2012. Results: Using a score of ≥4.05 to define fatigue, 39 of 52 (75%) participants were fatigued compared with 10 out of 31 (32%) healthy participants. The correlation between the FSS-Ar and the vitality domain of the RAND-36 was acceptable (r = -0.46). Factor analysis showed that items of the FSS-Ar measured one underlying construct, namely, fatigue. Test-retest reliability and internal consistency of the FSS-Ar was acceptable (intraclass correlation coefficient model 2,1 = 0.80; Cronbach’s alpha = 0.84). Conclusion: The Arabic version of the FSS demonstrated acceptable psychometric properties and was able to differentiate between patients with SLE or MS, and healthy subjects. Saudi Med J 2016; Vol. 37 (1): 73-78 doi: 10.15537/smj.2016.1.13055 How to cite this article: Al-Sobayel HI, Al-Hugail HA, AlSaif RM, Albawardi NM, Alnahdi AH, Daif AM, et al. Validation of an Arabic version of Fatigue Severity Scale . Saudi Med J 2016; 37: 73-8.

Background: It has been documented that remote limb ischemic preconditioning (rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized that osteopontin (OPN), transforming growth factor beta (TGF-β), apoptotic proteins (survivin and caspase-3) and oxidative stress play role in the renoprotective effects of rIPC. Materials and Methods: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: sham group, I/R group (left renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind limb ischemia just before renal ischemia). Each group was subdivided into 24, 48 and 72 h groups according to the time of sacrifice. We measured serum creatinine and blood urea nitrogen (BUN) at the baseline and end points. Also, left kidney was harvested at study end points for assessment of the expression of OPN, TGF-β, apoptotic proteins (survivin and caspase-3) and oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) in kidney tissues and histopathological examination. Results: Serum creatinine and BUN levels and histopathological damage score were significantly lower in rIPC group than I/R group (p < 0.005). Also, compared to I/R group, the levels of MDA and the expression of OPN, TGF-β and caspase-3 in kidney tissues were significantly lower in rIPC group, while the levels of SOD and GSH and the expression of survivin in kidney tissues were significantly higher in rIPC group at all time points (p ≤ 0.05). Conclusions: rIPC exhibited protective effects against renal I/R injury which might be due to inhibition of OPN expression, inflammatory cytokine TGF-β and caspase-3 and activation of anti-apoptotic protein survivin as well as improvement of oxidative stress in kidney tissues.

Aims: To investigate the effects of testosterone (Test) deficiency and testosterone replacement therapy (TRT) on the development of non-alcoholic fatty liver disease (NAFLD) and associated peripheral insulin resistance (IR) in male rats and to illustrate the underlying mechanisms of action. Materials and methods: male Sprague Dawley rats were divided into 3 groups as follows: 1) sham-operated group (n = 11), 2) ORCD-induced group (n = 9) exposed to orchidectomy (ORCD), achieved by complete surgical removal of testicles, and 3) ORCD + Test treated group (n = 10) (11 ng/mL Test propionate, 3x/week, S.C.). Results: Data revealed significant increases in final body, liver, visceral and subcutaneous fats weights with significant increases in fasting plasma glucose and insulin levels and HOMA-IR. Additionally, ORCD rats had higher UAC for measured glucose levels and insulin levels during OGTT and higher AUC for measured glucose levels during ITT. Interesting, higher serum and hepatic levels of TGs and CHOL and higher serum levels of LDL were seen in ORCD-induced rats. Mechanistically, significant increases in mRNA levels of SREBP-1, SREBP-2, ACC-1, FAS, HMGCOAR and HMGCOAS with significant increases in protein levels of both precursor and mature SREBP-1 and SREBP-2, PPAR-α, p-PPAR-α, CPT-1 and UCP-2 and significant lower protein levels p-AMPK and p-ACC-1 were detected in livers of ORCD rats. Test administration to ORCD-induced rats significantly ameliorated all of the above mentioned biochemical endpoints and reversed the effect of ORCD on mRNA and protein levels of these targets. In conclusion, Test deficiency could be an independent risk factor for the development of NAFLD by upregulation of lipid synthesis and disturb fatty acids oxidation whereas Test therapy is a protective strategy.

We tested the hypothesis that swim exercise can protect the articular cartilage from damages induced secondary to insulin-dependent diabetes mellitus in rats using the scanning electron microscopy and to monitor the blood levels of oxidative and antioxidative stress biomarkers that are known to be modulated in osteoarthritis (OA). A profound damage to the cartilage was observed in the diabetic rats. Our findings also show that swim exercise protects the knee joints from damage induced by diabetes as well as significantly inhibiting OA-induced upregulation of thiobarbituric acid reactive substances (TBARS) and tumor necrosis factor alpha (TNF-α) and augmented superoxide dismutase (SOD) inhibition by OA. Thus, we demonstrated an effective protection by swim exercise against diabetes-induced OA in a rat model of the disease.

Objectives to investigate the effect of testosterone on the cerebral cortex Bcl-2 expression and oxidative stress in a rat model of vascular dementia (VD). Methods Forty-eight Sprague-Dawley adult male rats were divided into four groups (n=12, each) as follows (i) untreated control, (ii) rats exposed to surgical permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (iii) rats exposed to BCCAO then received testosterone (0.5 mg/ kg S.C., three times/ week, S.C.) (BCCAO + Tes) for 4 weeks and (iv) rats exposed to BCCAO then received donepezil (3 mg/kg/ day; i.p.) (BCCAO + DON) for 4 weeks. Levels of acetylcholine and norepinephrine in the cerebral cortex were measured. Furthermore, the expression of Bcl-2 in the cerebral cortex and malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic [superoxide dismutase (SOD) and catalase (CAT)] anti-oxidants were determined. Histopathological studies of the cerebral cortex were performed. Results BCCAO decreased the expression of Bcl-2 as well as the central level of acetylcholine and norepinephrine as compared to control rats. Also, increased the cerebral cortex level of MDA and decreased the enzymatic and non-enzymatic antioxidant. Treatment with testosterone and donepezil increased acetylcholine and norepinephrine significantly when compared with BCCAO rats. Testosterone significantly increased the expression of Bcl-2 and antioxidant system with significant reduction in MDA. Conclusion Testosterone might employ neuroprotective effects through increasing the expression of Bcl-2 as well as ameliorating the oxidative stress induced by BCCAO in rat model of DA.

The aim of this study was to assess the level of food safety handling knowledge and practices among 1172 Lebanese university students (mean age 20.0 ± 1.6 SD) and to explore the association between their knowledge/practices and the socio-demographic and academic characteristics. Participants were undergraduate students enrolled in the Lebanese American University from different majors and years of study, from different areas of residence, living alone or with others, and having working or non-working mothers. They completed a questionnaire of 16 food handling practices and 14 food safety knowledge questions related to preparation, cross-contamination, storage and hygiene. On average, the students scored 53.6 ± 15.8% and 44.7 ± 14.3% on the knowledge and practices parts, respectively. Female students scored higher on both practices and knowledge questions than male students; however, the difference was significant (p

Malignant pleural mesothelioma (MPM) is a rare tumour. Exposure to asbestos is a well-established aetiological factor for MPM. Patients typically present with shortness of breath due to pleural effusion or chest pain in a more advanced stage. The diagnosis is usually suggested by imaging studies (unilateral pleural thickening; pleural effusion). An occupational history must be obtained. Cytological examination of the effusion can be diagnostic, but often shows equivocal results. Therefore, histology, including immunohistochemistry, is the gold standard. Thoracoscopy, a video-assisted surgical procedure or open pleural biopsy in a fused pleural space may be necessary to provide sufficient material for accurate histological diagnosis. There are three main histological types (epithelial, sarcomatous and mixed) with ~60% being epithelial. Data suggest the possible contribution of serum mesothelin-related proteins and osteopontin along with others as useful markers to support the diagnosis of mesothelioma; however, the precise role of these markers is yet to be defined.

Gastric ulcer is a common gastrointestinal disease. One suggested mechanism is increased oxidative stress. Puplished data showed that dehydroepiandrosterone (DHEA) may limit oxidative stress and lipid peroxidation.To investigate the protective effect of DHEA on indomethacin-induced gastric ulcers in rats.Forty male rats were randomly divided into four groups: l)receive the vehicle, 2) DHEA-treated group, 3) Indomethacin-induced ulcer group and 4) DHEA pretreated (prior to indomethacin) group. At the end of the experiment, rats were killed and the gastric contents were collected to determine the pH and acid concentration. Gastric mucosa was examined macroscopically and then parts of the tissues were collected for histopathological examination. Other parts of the gastric mucosa were homogenized to measure the levels of lipid peroxidation and oxidative stress parameters.Indomethacin-treated rats showed increased gastric acidity, acid concentration and ulcer index as compared to control rats. This is confirmed by histopathological studies. DHEA pre-treatment proir to indomethacin administration ameliorated all changes seen in the ulcered group.DHEA has a protective effect against indomethacin-induced gastric ulcers through decreasing acid secretion, prevention of lipid peroxidation and improving endogenous gastric antioxidant system.

This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all groups, and testicular levels of TBARS and superoxide dismutase (SOD) activity were measured. Epididymal semen analysis was performed, and testicular expression of Bcl-2, p53 and Bax was assessed by RT-PCR. Also, histopathological changes of the testes were examined microscopically. Administration of RES before or after cadmium chloride in rats improved semen parameters including count, motility, daily sperm production and morphology, increased serum concentrations of gonadotropins and testosterone, decreased testicular lipid peroxidation and increased SOD activity. RES not only attenuated cadmium chloride-induced testicular histopathology but was also able to protect against the onset of cadmium chloride testicular toxicity. Cadmium chloride downregulated the anti-apoptotic gene Bcl2 and upregulated the expression of pro-apoptotic genes p53 and Bax. Resveratrol protected against and partially reversed cadmium chloride testicular toxicity via upregulation of Bcl2 and downregulation of p53 and Bax gene expression. The antioxidant activity of RES protects against cadmium chloride testicular toxicity and partially reverses its effect via upregulation of BCl2 and downregulation of p53 and Bax expression.

Diabetic Nephropathy (DN) is one of most prevalent complications of Diabetes Mellitus (DM), therefore prevention of its development is a important field for researches. Quercetin is a plant flavenoid with hypoglycemic and antioxidant properties that is cla imed to have a reno-protective effect in diabetes. This study was designed to investigate the reno-preventi ve role of Quercetin treatment in terms of biochemi cal and pathological changes in diabetic rats and to de termine whether the effect is mediated through modulation of oxidative stress and Na + , K + ATPase expression and activity. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) Contro l group (C), (ii) Quercetin treated Control group ( CQ), (iii) Diabetic group (D), (iv) Diabetic Insulin tre ated group (DI), (v) Diabetic Quercetin treated gro up (DQ) and (vi) Diabetic Insulin and Quercetin treated gro up (DIQ). Systolic blood pressure was measured at t he end of the experiments (8 weeks). Retro-orbital blo od samples were used to determine the serum levels of glucose, HbA1c, urea, creatinine, Na + and K + . Renal homogenate levels of Na + , K + ATPase activity, Malondialdehyde (MDA0, Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) were measured. Semiquantitative reverse transcriptase-PCR Na + , K + ATPase expression assays and kidney histopathological examination were conducted. Treatment with either insulin or Quercetin alone resulted in partial rever sal of the biochemical and histopathological signs of neph ropathy in diabetic rats. This was associated with partial but significant amelioration of indicators of oxida tive stress and Na + , K + ATPase gene expression and activity. However only combined treatment by both insulin and Quercetin significantly improved all of the aforementioned parameters up to the control levels. These results suggested that combined therapy with insulin and Quercetin might be a useful preventive tool aga inst development of DN.

Aim To investigate the effects of testosterone on myocardial contractility, oxidative stress status and expression of sodium channel protein (Nav1.5) and inward rectifying K channels (Kir 2.x) in normal and orchidectomized (ORX) rats. Methods One hundred four rats were randomly assigned into four groups (n = 26, each) as follows: (i) untreated controls, (ii) testosterone treated, (iii) orchidectomized rats and (iv) orchidectomized, testosterone-treated rats. Treatments with the vehicle or testosterone were carried out for 12 weeks, three times per week. At the end of treatment, surface ECG, isolated heart, tissue oxidative stress and lipid peroxidation experiments were carried out on the cardiac tissues. Also, immunohistochemical examination for Nav1.5 and PCR detection of mRNA of Kir2.1, Kir2.2 and Kir2.4 subunits of K channels were carried out. Results Orchidectomy impaired cardiac contractile function parameters left ventricular developed pressure (LVDP) and the peaks of the positive and negative pressure derivatives (dP/dtmax and −dP/dtmax respectively), increased heart rate and prolonged QT and QTc intervals, elevated pro-oxidant state in rat's hearts and decreased the expression of Kir 2.1 but not Kir2.2, Kir 2.4 and Nav1.5 channels. Exogenous testosterone administration to orchidectomized rats restored heart contractility and shortened QT and QTc intervals to their normal values, ameliorated the generated pro-oxidant state and improved the expression of Nav1.5 and Kir2.1, but not Kir2.2 or Kir2.4 channels. Conclusion Testosterone improved cardiac contractility and shortened QT and QTc intervals in ORX rats. An effect that might be dependent of reduction in oxidative stress and enhancement of Kir2.1 channels but independent of Nav1.5 channel protein.

Arrhythmia is one of the major detrimental risk factors for cardiac arrest and death especially those associated with prolonged Q-T interval. Several antiarrythmic and cardiac agents prolong the Q-T interval as class I-a and class III anti-arrythmic agents. The cGMP is an important second messenger formed by the NO induced-guanylyl cyclase in response to L-arginine infusion. The aim of the present work is to investigate the relation between L-arginine infusion and different electrocardiograph (ECG) intervals. Isolated hearts from 6 male rabbits were perfused using Langendorff’s apparatus in which the perfusion fluid was ringer-Locke solution, applied at constant flow rate and was continuously bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Each heart served as its own control before infusion of adrenaline and then L-arginine at concentration of 3 mmol/L. With the help of Power Lab data acquisition and analysis system and Chart 7 program (ADInstruments Australia), the force of contraction, heart rate, and ECG were recorded for 5 min. NO generation and cGMP generation produces negative chronotropic effect with significant decrease in the heart rate from (125.2 ± 8.320) to (93.67 ± 7.04) /min. and significant prolongation of the Q–T interval 34% from (199.5 ± 22.35) to (268.4 ± 9.948) m.sec. and the Q-Tc by 24% from (291.0±35.98) to (361.2 ± 13.23) m.sec. L-arginine infusion with NO generation in isolated mammalian produces negative inotropic effects as well as prolongs Q-T and Q-Tc intervals. Key words: L-arginine, Q-T interval, arrhythmias, isolated heart.

Health care cost is consuming a large portion of the nation's gross domestic product while placing added economic burdens on physicians and their patients. With total joint replacement being one of the early-targeted procedures in the evolving health care environment, knee surgeons will benefit from developing a critical knowledge on health care reforms and their financial implications. The Medicare Access and Children's Health Insurance Program Reauthorization Act represents a cohesive movement toward value-based payment reform and contains several unchartered rulings that require detailed attention by knee surgeons. In this article, we provide a contextual framework of health care legislation that has led to the formation of the current health policy, and present a comprehensive summary and update on the Merit-Based Incentive Payment Systems and Alternative Payment Models reimbursement models.

In this study, we investigated the effects of grape seed extract (GSE) on the expression of osteopontin (OPN) and cyclooxygenase-2 (COX-2) in a rat model of spinal cord ischemia–reperfusion injury (SC-IRI). Fifty male rats were divided into 5 groups: control (CON); control + GSE (CON + GSE) (received GSE for 28 days); sham operated (Sham); IRI; and IRI + GSE. SC-IRI was induced by clamping the aorta just above the bifurcation for 45 min, and then the clamp was released for 48 h for reperfusion. IRI + GSE group received GSE for 28 days before SC-IRI. Sensory, motor, and placing/stepping reflex assessment was performed. Prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBARs), and total antioxidant capacity (TAC) were measured in spinal cord homogenate. Immunohistochemical examination of the spinal cord for OPN and COX-2 were carried out. SC-IRI resulted in significant increase in plasma nitrite/nitrate level and spinal cord homogenate levels of TBARs and PGE2, and OPN and COX-2 expression with significant decrease in TAC. GSE improves the sensory and motor functions through decreasing OPN and COX-2 expression with reduction of oxidative stress parameters. We conclude a neuroprotective effect of GSE in SC-IRI through downregulating COX-2 and OPN expression plus its antioxidants effects.

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and −dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, −dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.

Recently, guidelines on the management of hyperglycemia in type 2 diabetes were released by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) as their formally adopted position statement. These guidelines are different from the previously published documents. They introduced a nonalgorithmic patient-centered approach that stressed the principles of individualization of care based on several important patients’ attributes. They affirmed the role of lifestyle modification as a basic requirement, metformin as the first line pharmacological therapy and individually-tailored basis for the choice of the second and third line drugs. In this paper, the authors reflect on these guidelines from the world-wide practicing physicians’ view point. Key words: Diabetes, Guidelines, Hyperglycaemia, Patient-centered care, American Diabetes Association, European Association for the Study of Diabetes.

Patients with any endocrine condition wishing to observe the fasting during Ramadan may seek advice from their primary care or specialist physician. In healthy people, there are minimal changes in the metabolic and hormonal parameters during fasting. However, management of common endocrine conditions may need some adjustments. Aside from diabetes mellitus, endocrine and metabolic conditions commonly seen in clinical practice include hypothyroidism, hyperthyroidism, adrenal disease, pituitary diseases and obesity. Adjustments in medications are based on physiological and clinical aspects of these conditions, and on sound knowledge of the pharmacological characteristics of all prescribed medications. Thyroid hormones should be taken on an empty (or near empty) stomach and not be followed by food by 0.5-1 hour according to the patient’s life style. Glucocorticoids should be taken in the same manner at either end of the fasting period, or changed to an extended release preparation taken on its own or in combination with hydrocortisone with Iftar. Management of hypogonadism is essentially the same both during and outside of Ramadan in both men and women. Growth hormone may be taken in the same manner in both children and adults. Patients with diabetes insipidus should be careful with fluid balance, and take adequate doses of desmopresin in widely spaced dosing for maximum benefit. Spontaneous hypoglycemia may present for the first time during Ramadan, and suggestive symptoms should alert the physician to this diagnosis. Ramadan-type intermittent fasting provides an opportunity for weight loss but this is often lost as evening time feasting seems to offset any benefit from daytime fasting. In conclusion, common endocrine conditions are managed along the same lines of good clinical practice, sound understanding of physiology and pharmacology, coupled with modern approaches of individualized and ethnically competent care. Key words: Ramadan Fasting, Ethnic, Thyroid, Adrenal, Pituitary, Bone health, Obesity