ß-Hydroxybutyrate and melatonin suppress maladaptive UPR, excessive autophagy and pyroptosis in Aß 1-42 and LPS-Induced SH-SY5Y cells.

BACKGROUND: Alzheimer's disease is a neurological disease characterized by the build-up of amyloid beta peptide (Aß) and lipopolysaccharide (LPS), which causes synapse dysfunction, cell death, and neuro-inflammation. A maladaptive unfolded protein response (UPR), excessive autophagy, and pyroptosis aggravate the disease. Melatonin (MEL) and hydroxybutyrate (BHB) have both shown promise in terms of decreasing Aß pathology. The goal of this study was to see how BHB and MEL affected the UPR, autophagy, and pyroptosis pathways in Aß1-42 and LPS-induced SH-SY5Y cells. MATERIALS AND METHODS: Human neuroblastoma SH-SY5Y cells were treated with BHB, MEL, or a combination of the two after being exposed to A ß1-42 and LPS. Cell viability was determined using the MTT test, and gene expression levels of UPR (ATF6, PERK, and CHOP), autophagy (Beclin-1, LC3II, P62, and Atg5), and pyroptosis-related markers (NLRP3, TXNIP, IL-1ß, and NFκB1) were determined using quantitative Real-Time PCR (qRT-PCR). For statistical analysis, one-way ANOVA was employed, followed by Tukey's post hoc test. RESULTS: BHB and MEL significantly increased SH-SY5Y cell viability in the presence of A ß1-42 and LPS. Both compounds inhibited the expression of maladaptive UPR and autophagy-related genes, as well as inflammatory and pyroptotic markers caused by Aß1-42 and LPS-induced SH-SY5Y cells. CONCLUSION: BHB and MEL rescue neurons in A ß1-42 and LPS-induced SH-SY5Y cells by reducing maladaptive UPR, excessive autophagy, and pyroptosis. More research is needed to fully comprehend the processes behind their beneficial effects and to discover their practical applications in the treatment of neurodegenerative disorders.

Therapeutic potential of aquatic Stevia extract in alleviating endoplasmic reticulum stress and liver damage in streptozotocin-induced diabetic rats.

BACKGROUND: Misfolded proteins accumulate in the liver due to endoplasmic reticulum stress (ERS) caused by high blood glucose levels in diabetes. This triggers the unfolded protein response (UPR), which if persistently activated, results in cellular dysfunction. Chronic ER stress increases inflammation, insulin resistance, and apoptosis. There is growing interest in using native plants and traditional medicine for diabetes treatment. The stevia plant has recently gained attention for its potential therapeutic effects. This study investigates the protective effects of aquatic stevia extract on liver damage, ER stress, and the UPR pathway in streptozotocin (STZ)-induced diabetic rats. METHODS: Rats were randomly divided into four groups: a control group that received 1 ml of water; a diabetic group induced by intraperitoneal injection of STZ (60 mg/kg); a diabetic group treated with metformin (500 mg/kg); and a diabetic group treated with aquatic extracts of stevia (400 mg/kg). After 28 days, various parameters were assessed, including inflammatory markers, oxidative stress indices, antioxidant levels, gene expression, stereology, and liver tissue pathology. RESULT: Compared to the diabetic control group, treatment with stevia significantly decreased serum glucose, liver enzymes, inflammatory markers, and oxidative stress while increasing body weight and antioxidant levels. Additionally, stevia extract manipulated UPR gene expression and reduced apoptosis pathway activation. Histological examination revealed improved liver tissue morphology in stevia-treated diabetic rats. CONCLUSION: These findings suggest that aquatic stevia extract mitigates ER stress in diabetic rats by modulating the IRE-1 arm of the UPR and apoptosis pathways, highlighting its potential therapeutic benefits for diabetes-related liver complications.

Targeting apoptosis and unfolded protein response: the impact of ß-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) plays a significant role in the mortality associated with kidney cancer. Targeting biological processes that inhibit cancer growth opens up new treatment possibilities. The unfolded protein response (UPR) and apoptosis have crucial roles in RCC progression. This study investigates the impact of ß-hydroxybutyrate (BHB) on ccRCC cells under glucose deprivation resembling as a ketogenic diet. METHOD: Caki-1 ccRCC cells were exposed to decreasing glucose concentrations alone or in combination with 10 or 25 mM BHB during 48 and 72 h. Cell viability was determined using MTT assay. The mRNA expression level of apoptosis-and UPR-related markers (Bcl-2, Bax, caspase 3, XBP1s, BIP, CHOP, ATF4, and ATF6) were assayed by qRT-PCR. RESULTS: Cell viability experiments demonstrated that combining different doses of BHB with decreasing glucose levels initially improved cell viability after 48 h. Nevertheless, this trend reversed after 72 h, with higher impacts disclosed at 25 mM BHB. Apoptosis was induced in BHB-treated cells as caspase-3 and Bax were increased and Bcl-2 was downregulated. BHB supplementation reduced UPR-related gene expression (XBP1s, BIP, CHOP, ATF4, and ATF6), revealing a possible mechanism by which BHB affects cell survival. CONCLUSION: This research emphasizes the dual effect of BHB, initially suppressing cell- survival under glucose deprivation but eventually triggering apoptosis and suppressing UPR signaling. These data highlight the intricate connection between metabolic reprogramming and cellular stress response in ccRCC. Further research is recommended to explore the potential of BHB as a therapeutic strategy for managing ccRCC.

Improved therapy for clear cell renal cell carcinoma: beta-hydroxybutyrate and quercetin target hypoxia-induced angiogenesis and multidrug resistance.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a form of kidney cancer characterized by dysregulated angiogenesis and multidrug resistance. Hypoxia-induced tumor progression plays a crucial role in ccRCC pathogenesis. Beta-hydroxybutyrate (BHB) and quercetin (QCT) have shown potential in targeting angiogenesis and drug resistance in various cancer types. This study investigates the combined effects of BHB and QCT in hypoxia-induced Caki-1 cells. METHODS: Caki-1 cells were subjected to normoxic and hypoxic conditions and treated with BHB, QCT, or a combination of both. Cell-viability was assessed using the MTT assay, and mRNA expression levels of key angiogenesis-related genes (HIF-1α/2α, VEGF, Ang-1, Ang-2, and MDR4) were quantified through real-time PCR during 24 and 48 h. RESULTS: BHB and QCT treatments, either alone or in combination, significantly reduced cell-viability in Caki-1 cells (p < 0.05). Moreover, the combined therapy demonstrated a potential effect in downregulating the expression of angiogenesis-related genes and MDR4 in hypoxia-induced cells, with a marked reduction in HIF-1α/2α, VEGF, Ang-1, and MDR4 expression (p < 0.05). The expression of Ang-2 increases significantly in presence of BHB combined QCT treatment. CONCLUSION: This study highlights the promising potential of a combination therapy involving BHB and QCT in mitigating angiogenesis and MDR4 expression in hypoxia-induced ccRCC cells. These findings support further investigation into the underlying mechanisms and warrant clinical studies to evaluate the therapeutic value of this combined treatment for ccRCC patients. This research provides new insights into addressing the challenges posed by angiogenesis and drug resistance in ccRCC.

The effects of soymilk plus probiotics supplementation on cardiovascular risk factors in patients with type 2 diabetes mellitus: a randomized clinical trial.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular diseases. This study aimed to assess the effects of soymilk plus probiotics co-administration on cardiovascular risk factors in T2DM patients. METHODS: One hundred patients with T2DM (aged 40-75 years old) were randomly assigned into 4 groups (soymilk + probiotics supplement, soymilk + placebo, conventional milk + placebo, and probiotics supplement) for 6 weeks. Standard protocols were followed for the collection of fasting blood samples, dietary intakes, and anthropometric measurements. RESULTS: It was shown that soymilk + probiotics consumption significantly decreased diastolic blood pressure (DBP) (p = 0.001), triglycerides (TG) (P < 0.001), total cholesterol (TC) (p < 0.01), and insulin (P < 0.003) levels and significantly increased high-density lipoprotein cholesterol (HDL-C) (P = 0.002) levels. Soymilk + placebo administration significantly decreased DBP (p = 0.01), insulin (p = 0.006), and TG (p = 0.001) levels and significantly increased HDL-C (p = 0.03) levels. A significant decrease in insulin (p = 0.003) and systolic blood pressure (SBP) (p = 0.01) levels and an increase in HDL-C (p = 0.04) levels were observed after supplementation with probiotics. Findings from between-group comparisons showed a significant decrease in SBP levels in the probiotics supplement group compared to conventional milk group (p < 0.05). CONCLUSION: Soymilk and probiotics consumption might improve some cardiovascular risk factors in patients with T2DM. However, possible synergic effects while consumption of soymilk plus probiotics supplement didn't show in this study which warranted further research.

Gingivitis from the Viewpoint of Traditional Persian Medicine.

BACKGROUND: Gingivitis is among the top general health problems in the world, especially in developing countries. Meanwhile, it may be associated with pulmonary and cardiovascular diseases. In a qualitative study, we tried to identify the corresponding terminology to gingivitis in traditional Persian medicine (TPM) and to explain its potential mechanisms, treatments, and prevention characteristics. METHODS: In a literature review, 4 modern textbooks and 18 related articles, 2 traditional medical dictionaries and 12 traditional medical and 4 traditional pharmaceutical texts were assessed by a specific method. Initially, traditional scripts were searched for signs and symptoms of gingivitis as well as related keywords such as bleeding, swollen and loosen gum, oral or gingival ulcers, teeth, or gingival pain. Then the disease/s or disorder/s, which matched gingivitis in TPM, was appraised in details. Finally, potential mechanisms, prevention and therapeutic protocols presented by TPM were collated and summarized. RESULTS: "Lasse-e-Dâmiyeh" (bleeding gum) or "Khoon-Reezi az Goosht-e Bon-e Dandân" (bleeding from under teeth flesh) was the main disease comparable to gingivitis. Based on TPM, the leading etiologies are insufficient gum feeding mechanism, pouring and gathering of excessive fluid in the gum and accumulation of excessive blood in it or in the whole body. Although there were remarkable similarities in the subjects of different TPM texts over the centuries, particularly in oral and teeth hygiene and overall approach to gingivitis, we faced notable differences in recipes (herbal drugs) that each text proposed. CONCLUSION: While there are overlapping terminologies to gingivitis in TPM, "Lasse-e-Dâmiyeh" is the closest disease that relates to it. Meanwhile, adjusting diet and lifestyle, having appropriate oral hygiene, obtaining a vast variety of herbal medications, cupping, phlebotomy, leech therapy, etc. are the different TPM modalities for the prevention and treatment of gingivitis that can be considered as therapeutic and/or research issues.

Rhus Coriaria L. (Sumac) in Patients with Hyperlipidemia; A Double Blind Randomized Clinical Trial.

BACKGROUND: Lipid lowering effect of sumac is investigated in multiple animal studies with promising results. However, its clinical efficacy is not investigated adequately. This study is aimed to evaluate the lipid lowering effect of sumac in patients with Hyperlipidemia in a double blind randomized controlled trial. METHODS: Eighty patients with Hyperlipidemia according to NCEP-ATP III criteria were randomly allocated to receive the Rhus Coriaria L. (1000 mg/day) or placebo for two months. The patients were evaluated in terms of the serum triglyceride, total LDL, and HDL cholesterol. Systolic and diastolic blood pressures along with serum biochemistry profile including fasting blood sugar, liver and kidney function tests and complete blood count were evaluated before the enrolment of patients and after the intervention. RESULTS: No significant difference was observed between the sumac and placebo groups in term of mean reductions in total and LDL cholesterol and triglyceride levels. A significant increase in mean serum HDL cholesterol level was observed in the sumac group (41.18±8.2 vs. 44.65±8.4, P=0.001) after 2 months of intervention. CONCLUSION: The study showed significant HDL cholesterol increasing effect of sumac supplementation in patients with Hyperlipidemia.

Proton-pump inhibitor-induced bone loss is preventable by concomitant use of a long-acting somatostatin analogue.

Objectives: Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model. Materials and Methods: Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis. Results: The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (P<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (P<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group. Conclusion: This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.

Prevalence, patterns, and disclosure of complementary and alternative medicine (CAM) use among patients with thyroid diseases: A cross-sectional study in Iran.

Introduction: Complementary and alternative medicine (CAM) has gained popularity as a therapeutic approach outside conventional medicine for various medical conditions. This study aimed to assess the prevalence, patterns, and disclosure of CAM use among patients with thyroid diseases in Iran. Methods: This descriptive-analytic cross-sectional study involved patients with thyroid diseases who were visiting Internal Medicine Clinics in Shiraz. The use of CAM was assessed by employing the Persian edition of the I-CAM-Q (I-CAM-IR) questionnaire. Results: A total of 343 individuals took part in the study, and 85.4 % of them reported using CAM within the previous 12 months. Medicinal herbs were the most commonly used CAM modality (63 %). CAM use was primarily for enhancing overall well-being. Among self-care CAM practices, praying was the most frequently employed (70 %). Women exhibited a significantly higher CAM utilization rate (four times greater) compared to men (p < 0.001), with herbs being more commonly used by women (p < 0.001). A significant proportion of participants did not inform their physicians about their CAM use, and 46 % experienced significant benefits from using CAM. Conclusion: This study highlights a high prevalence of CAM use, particularly herbal remedies, among Iranian patients with thyroid diseases.

Factors disrupting the continuity of care for patients with chronic disease during the pandemics: A systematic review.

Background and Aims: Continuous routine care is necessary to prevent long-term complications of chronic diseases and improve patients' health conditions. This review study was conducted to determine the factors disrupting continuity of care for patients with chronic diseases during the pandemic. Methods: All original articles published on factors disrupting continuity of care for patients with chronic disease during a pandemic between December 2019 and June 28, 2023, in PubMed, Web of Science, Scopus, and ProQuest databases were searched. Selection of articles, data extraction, and qualitative evaluation of articles (through STROBE and COREQ checklist) were done by two researchers separately. Data graphing form was used to extract the data of each study and then the data were classified by thematic analysis method. Results: Out of 1708 articles reviewed from the databases, 22 were included. The factors disrupting the continuity of care for patients with chronic diseases during the epidemics were classified into two main categories: patient-side factors and health system-side factors. Patient-side factors including psychological, individual and social, disease-related, and health system-side factors including provider access, health system institutional, and infrastructural and financial problems were among the subcategories disrupting the continuity of care for patients with chronic diseases during the pandemic. Based on the studies, psychological factors and access to the provider were among the most frequent factors affecting the continuity of care for patients with chronic diseases in the pandemic. Conclusion: Considering the factors disrupting the continuity of care and applying appropriate interventions based on them, can guarantee the continuity of providing services to chronic patients in health crises.

The Effects of Ginger (Zingiber Officinale Roscoe) on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

Nonalcoholic fatty liver disease (NAFLD) is a prominent etiological factor for liver cirrhosis worldwide. It is frequently associated with obesity, diabetes, dyslipidemia, and hypertension. The objective of this study is to assess the efficacy and safety of ginger (Zingiber officinale Roscoe) supplementation in patients with type 2 diabetes mellitus (T2DM) who have NAFLD. In a two-arm, double-blind, placebo-controlled clinical trial, seventy-six patients diagnosed with both T2DM and NAFLD were randomly assigned to receive either ginger powder capsules (1000 mg, twice daily) or placebo capsules (administered in the same manner) for a period of three months. Anthropometric measurements, blood pressure readings, biochemical profiles, and imaging parameters were assessed before and after the intervention. Safety measures were also evaluated. In both the ginger and placebo groups, there was a significant reduction in mean body mass index (BMI), waist and hip circumferences, as well as liver transaminase levels. Moreover, significant improvements in mean systolic and diastolic blood pressures were observed in the ginger group (p = 0.02 and < 0.0001, respectively). Within the ginger group, there was a decrease in serum insulin levels and insulin resistance (HOMA-IR) (p = 0.002 and 0.004, respectively). Furthermore, the ginger group exhibited an improvement in serum HDL-cholesterol level (p = 0.01). However, there were no significant changes in the assessed inflammatory markers or the indices obtained from fibroscan imaging, including steatosis percent and controlled attenuation parameter. This study demonstrates that ginger supplementation can significantly improve mean systolic and diastolic blood pressures. However, it does not have a significant impact on inflammatory markers or fibroscan imaging indices. Nonetheless, the three-month use of ginger improves serum insulin level, insulin resistance (HOMA-IR), and HDL-cholesterol level compared to baseline values. Further investigations with longer durations and larger sample sizes are recommended.

"Protective effects of artichoke extract and Bifidobacterium longum on male infertility in diabetic rats".

Background: Diabetes is a major global health concern and plays a significant role in male infertility and hormonal abnormalities by altering the tissue structure of spermatogenic tubes and decreasing the number of spermatogonia. This study investigated the effect of artichoke (Cynara scolymus L) hydroalcoholic extract and Bifidobacterium longum probiotic on sexual hormones, oxidative stress, apoptosis pathway, and histopathological changes in testicular tissues of diabetic rats to find an adjuvant therapy to manage the infertility complications of diabetes. Methods: In this experiment, 96 male-rats were randomly selected from eight groups. Control, Sham (normal saline), DM group (IP injected with 60 mg/kg STZ), Cynara (400 mg/kg hydroalcoholic extract of Cynara scolymus L), BBL (received 1 × 109 CFU/ml/day Bifidobacterium longum), DM + Cynara, DM + BBL, and DM + Cynara + BBL groups. After 48 days of orally gavage, serum level of FBS (fasting blood sugar), Malondi-aldehyde (MDA), Total-Anti-Oxidant Capacity (TAC), FSH (Follicle-stimulating hormone), LH (Luteinizing hormone), Testosterone, Testis mRNA-expressions of Protamin (prm1), BCL2, and Caspase-9 genes, as well as stereological changes were measured. Results: In comparison to the diabetic group, the hydroalcoholic extract of Cynara scolymus L combined with the probiotic Bifidobacterium longum resulted in a substantial decrease in FBS (p < 0.001) and MDA(p < 0.05) concentrations, and the expression of the Caspase-9 gene (1.33-fold change). In addition, serum levels of TAC, LH, FSH, Testosterone were significantly increased (p < 0.05). mRNA expression of protamine (p = 0.016) and BCL2 (0.72-fold change) were detected. Furthermore, in comparison with diabetic rats, the Cynara scolymus L-and Bifidobacterium longum-treated groups showed a significant increase in the number of sexual lineage cells, total weight, sperm count, motility, normal morphology, volume of the testis, and volume and length of seminiferous tubules (p < 0.05). Conclusion: The findings demonstrated that Cynara scolymus L extract and Bifidobacterium longum supplement had great therapeutic potential, including antioxidant, anti-apoptotic, anti-diabetic, fertility index improvement, and sex hormone modulators.

Pantoprazole-Induced Bone Loss through Gastrin Secretion: A Stereological Study.

Background: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. Methods: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation. Results: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. Conclusion: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.

New concepts in regulation and function of the FGF23.

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.

Serum androgens and prolactin levels in patients with keratoconus.

CLINICAL RELEVANCE: There is growing evidence for the involvement of sex hormones in the pathogenesis of keratoconus. BACKGROUND: This study aimed to evaluate serum androgen and prolactin levels in patients suffering from keratoconus. METHODS: One hundred and two subjects were enrolled in the keratoconus (76 patients) and control (26 subjects) groups in a cross-sectional survey. Topographic evaluation of the cornea was undertaken for all enrolled participants. Serum testosterone, dehydroepiandrosterone sulphate (DHEAS), prolactin (PRL), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were measured in all subjects. RESULTS: There was no significant difference in demographic characteristics between the study groups. Significantly higher mean serum levels of DHEAS (3.71 ± 2.23 vs. 2.53 ± 1.77 µg/mL; P = 0.009) and T (6.18 ± 3.80 vs. 1.57 ± 1.76 ng/mL; P < 0.001) were observed in men with keratoconus compared to controls. In females, there were also higher mean levels of DHEAS (2.40 ± 1.57 vs. 2.18 ± 0.72 µg/mL; P = 0.355) and T (0.78 ± 0.96 vs. 0.32 ± 0.13 ng/mL; P < 0.001) in patients with keratoconus but only T level reached the statistically significant level of difference. Also, the mean serum PRL level was significantly higher in women with keratoconus compared to control (13.33 ± 17.85 vs. 4.63 ± 3.10 ng/mL; P < 0.001). There was no significant difference between serum FSH and LH levels between study groups. CONCLUSION: In patients with keratoconus, serum PRL in females and serum androgen levels in both genders are elevated.

Association between Nontraditional Risk Factors and Calculated 10-Year Risk of Atherosclerotic Cardiovascular Disease in a Large General Population: Based on the Pars Cohort Study.

Background: While the traditional risk factors of atherosclerotic cardiovascular disease (ASCVD) have been well-established, the evolving role of nontraditional risk factors is not apparent. This study aimed to evaluate the association between nontraditional risk factors and the calculated 10-year ASCVD risk in a general population. Methods: This cross-sectional study was conducted using the Pars Cohort Study data. All inhabitants of the Valashahr district in southern Iran, aged 40-75 years, were invited (2012-2014). Patients with a history of cardiovascular disease (CVD) were excluded. The demographic and lifestyle data were collected using a validated questionnaire. Multinomial logistic regression analysis was used to evaluate the association between the calculated 10-year ASCVD risk and the nontraditional risk factors of CVD, including marital status, ethnicity, educational level, tobacco and opiate consumption, physical inactivity, and psychiatric disorders. Results: Of 9264 participants (mean age =52.2±9.0 y; 45.8% male), 7152 patients met the inclusion criteria. In total, 20.2%, 7.6%, 36.3%, 56.4%, and 46.2% of the population were cigarette smokers, opiate consumers, tobacco consumers, ethnically Fars, and illiterate, respectively. The prevalence rates of low, borderline, and intermediate-to-high 10-year ASCVD risks were 74.3%, 9.8%, and 16.2%, respectively. In multinomial regression, anxiety (adjusted odds ratio [aOR], 0.58; P<0.001) was significantly associated with a lower ASCVD risk, whereas opiate consumption (aOR, 2.94; P<0.001) and illiteracy (aOR, 2.48; P<0.001) were significantly associated with a higher ASCVD risk. Conclusion: Nontraditional risk factors are associated with the 10-year ASCVD risk and, thus, might be considered besides traditional ones for ASCVD in preventive medicine and health policies.

Depression, Testosterone concentration, sexual dysfunction and methadone use among men with hypogonadism and HIV Infection.

Low testosterone levels are associated with depression and impaired sexual performance. We examined the association between hypogonadism, sexual function and depression among men with HIV infection in Shiraz, Iran. A total of 237 male HIV-positive patients referred to voluntary counseling centers were recruited based on convenience sampling from May to October 2010. All patients provided informed consent and completed the Beck Depression Inventory (BDI-II) and Brief Male Sexual Function Inventory (BMSFI). Blood samples were collected after an overnight fast to measure free testosterone (FT) concentration. Hypogonadism was found in 68 % of the participants, and about 68.8 % had moderate and severe depression. Serum FT levels were significantly lower in patients with depression and a direct association was found between the risk of hypogonadism and increased BDI-II score. Among methadone nonusers and nondepressed patients, an inverse association was found between hypogonadal and eugonadal men in the sexual drive, erectile and ejaculatory function domains of the BMSFI. However, there was no significant association between methadone user status and depression. Depression and hypogonadism had a reciprocal effect. Depression and methadone use were associated with hypogonadism and had a significant effect on sexual function.

Proximal muscle weakness as the sole manifestation of Cushing's disease, misdiagnosed as dermatomyositis: a case report.

BACKGROUND: Cushing's syndrome consists of signs and symptoms related to prolonged exposure to high levels of glucocorticoid, and should be considered in individuals with the discriminatory signs and symptoms. Proximal myopathy is an important discriminatory sign. CASE PRESENTATION: We report the case of a 36-year-old Iranian man who presented with proximal muscle weakness. He visited a rheumatologist in an outpatient clinic, and according to proximal muscle weakness and heliotrope rash (based on the rheumatologist's notes) with the impression of dermatomyositis, prednisolone and azathioprine were prescribed for him that did not improve his clinical status and he was gradually wheelchair dependent. He was admitted to the hospital for evaluation of paraneoplastic syndromes. Standard laboratory tests and imaging were unremarkable, other than a brain magnetic resonance imaging that demonstrated a 30 × 12 mm homogeneously enhancing mass in the sellar region with extension to the suprasellar area. He had serum cortisol of 295 ng/mL, and adrenocorticotropic hormone of 222 pg/mL (on 5 mg prednisolone twice daily), with a diagnosis of Cushing's disease. He underwent two sessions of trans-sphenoidal surgery 4 months apart. After the first surgery, the proximal muscle weakness improved dramatically and he was walking with the aid of a walker, and after the second surgery he is walking without any aids. CONCLUSION: This case report emphasizes the high diagnostic importance of proximal muscle weakness as the sole presenting manifestation of Cushing's syndrome/disease.

Efficacy of Ginger Supplementation in Relieving Persistent Hypothyroid Symptoms in Patients with Controlled Primary Hypothyroidism: A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Primary hypothyroidism is a common disease. Some patients have persistent symptoms despite normal serum thyroid-stimulating hormone (TSH) levels. Ginger is reported to be beneficial in relieving similar symptoms. Our aim was to evaluate the efficacy of ginger supplementation in relieving persistent symptoms in these patients. In this randomized, double-blind, placebo-controlled clinical trial, 60 hypothyroid patients aged 20-60 years with normal serum TSH concentrations were randomly allocated to two equal parallel study groups of ginger (500 mg twice a day) or placebo for 30 days. Hypothyroid symptoms were evaluated as the primary outcome using the Thyroid Symptom Rating Questionnaire (ThySRQ) before and after the intervention. Anthropometric measures and laboratory indices including TSH, triglyceride (TG), total cholesterol (TChol), and fasting blood sugar (FBS) were considered as secondary outcomes. A significant lower mean total ThySRQ score (8.63 ± 5.47 vs. 15.76 ± 6.09, P < 0.001) was observed in the ginger group compared to the control group. Ginger led to significant improvements in the mean scores of the weight gain, cold intolerance, constipation, dry skin, appetite, memory loss, concentration disturbance, and feeling giddy or dizzy domains (P < 0.001). However, no significant improvements were observed in hair loss, nail fragility, hearing, hoarseness, speech, and depression or feeling down (P > 0.05). Ginger supplementation also led to a significant decrease in body weight, body mass index, waist circumference, serum TSH, FBS, TG, and TChol levels compared to the placebo. In summary according to preliminary results of this study, ginger supplementation can help relieve persistent hypothyroid symptoms. Also, it may have beneficial effects in terms of weight reduction and regulation of the FBS and lipid profile in hypothyroid patients.

Cosmetic use and serum level of lead (not cadmium) affect bone mineral density among young Iranian women.

Bone mineral density is a crucially important index for skeletal health. A low amount of bone density (osteoporosis) is a common health problem among men and especially women. Among different parts of the body, women's face is the area on which many types of (facial) cosmetics are routinely applied. The aims of this study were to measure the association of cosmetic use with BMD of the lumbar spine and femoral neck among young female students. This is a cross-sectional study on 65 female students in the 2017 academic year. The study participants were students at Shiraz University of Medical Sciences who were selected randomly using phone directory sampling method. Based on the results of multiple linear regression, adjusted for several important covariates, cosmetic use is inversely associated with the BMD z-scores. Lead was significantly associated with trochanteric z-score (B = -0.002 to 95% CI = -0.004 to -0.0003, p = 0.02) and total lumbar z-score (B = -0.002 to 95% CI = -0.004 -0.0005, p = 0.01). In the present study, duration of using cosmetics was significantly associated with BMD of key skeletal regions. The big market of cosmetics in many countries especially those in the Middle East is highly a vastly neglected health issue. Many more observational prospective or interventional studies are required to understand the benefits and hazards caused by cosmetics in women.