A randomized, double-blind placebo-controlled add-on trial to assess the efficacy, safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus.

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three-month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.

Evaluation of wound-healing efficiency of a functional Chitosan/Aloe vera hydrogel on the improvement of re-epithelialization in full thickness wound model of rat.

OBJECTIVE: Chitosan-based hydrogels as wound dressings are expected to improve the efficiency of the wound-healing process. Fabrication of the composite structure of Aloe vera and biopolymeric hydrogels has been demonstrated to promote the wound-healing process through protection against a wide spectrum of microbes, and enhanced cell adhesion and differentiation. Therefore, the present study investigates to development of improved CHO/Aloe hydrogel for improving the wound-healing process in an animal model. MATERIALS AND METHODS: CHO hydrogel with Aloe was prepared, and its properties were evaluated in terms of viscosity, antibacterial activity, and ints In-vivo wound-healing efficiency in full-thickness wounds of rat models. Physical examination of wound-healing efficiency of CHO/Aleo hydrogel was evaluated by analyzing total wound closure, recovery percentage, and the epiderm thickness of wounds. Histological evaluation was performed using hematoxylin and eosin staining to evaluate the re-epithelialization, inflammatory response, granulation tissue formation, and fibrotic tissue formation. RESULTS: The results showed a significantly higher wound-healing rate of the CHO/Aleo group compared to other groups at 3,7,14 days (p < 0.05). After 14 days of treatment, the best healing effect was observed in the CHO/Aleo gel with the highest tissue tension compared with other groups (p < 0.05). Histological findings indicated a significant difference in inflammatory response between control and treatment groups after three days of treatment (p < 0.05). Epidermal thickness was also significantly thicker in the CHO/Aleo gel group than others (p < 0.05). CONCLUSION: The present study an improved the effective topical drug-delivery system by CHO/Aloe hydrogel with the potential to reduce inflammation over time, allowing the body to recover more quickly and better re-epithelialization for improving the wound-healing procedures.

Effectiveness of IT-based interventions on self-management in adult kidney transplant recipients: a systematic review.

BACKGROUND: Kidney transplant outcomes are broadly associated with transplant recipients' capacity in following a complex and continuous self-management regimen. Health information technology has the potential to empower patients. This systematic review aimed to determine the impacts of IT-based interventions for self-management in kidney transplant recipients. METHODS: A comprehensive investigation was performed in MEDLINE (via PubMed) and EMBASE (via Scopus) in April 2019. Eligible studies were the randomized controlled trials which aimed to design an automated IT-based intervention. All English papers including adult kidney transplant recipients were included. To assess the clinical trial's quality, Cochrane Collaboration's assessment tool was employed. The articles were integrated based on category of outcomes, characteristics of interventions, and their impact. The interventions were classified based on the used IT-based tools, including smart phones, coverage tools, computer systems, and a combination of several tools. The impact of interventions was defined as: (1) positive effect (i.e. statistically significant), and (2) no effect (i.e. not statistically significant). RESULTS: A total of 2392 articles were retrieved and eight publications were included for full-text analysis. Interventions include those involving the use of computerized systems (3 studies), smart phone application (3 studies), and multiple components (2 studies). The studies evaluated 30 outcomes in total, including 24 care process and 6 clinical outcomes. In 18 (80%) out of 30 outcomes, interventions had a statistically significant positive effect, 66% in process and 33% in clinical outcomes. CONCLUSIONS: IT-based interventions (e.g. mobile health applications, wearable devices, and computer systems) can improve self-management in kidney transplant recipients (including clinical and care process outcomes). However, further evaluation studies are required to quantify the impact of IT-based self-management interventions on short- and long-term clinical outcomes as well as health care costs and patients' quality of life.

Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial.

Curcumin is proposed as a potential treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus entrance, encapsulation and replication, and modulating various cellular signaling pathways. In this open-label nonrandomized clinical trial, efficacy of nano-curcumin oral formulation has been evaluated in hospitalized patients with mild-moderate COVID-19. Forty-one patients who fulfilled the inclusion criteria were allocated to nano-curcumin (n = 21) group (Sinacurcumin soft gel, contains 40 mg curcuminoids as nanomicelles, two capsules twice a day) or control (n = 20) group, for 2 weeks. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period. Most of symptoms including fever and chills, tachypnea, myalgia, and cough resolved significantly faster in curcumin group. Moreover, SaO2 was significantly higher in treatment group after 2, 4, 7, and 14 days of follow-up and lymphocyte count after 7 and 14 days. Duration of supplemental O2 use and hospitalization was also meaningfully shorter in treatment group. It is also noteworthy to mention that no patient in treatment group experienced deterioration of infection during follow-up period, but it occurred in 40% of control group. Oral curcumin nano-formulation can significantly improve recovery time in hospitalized COVID-19 patients. Further randomized placebo controlled trials with larger sample size are recommended.

A randomized, double-blind, placebo-controlled, clinical trial to evaluate the benefits of Nigella sativa seeds oil in reducing cardiovascular risks in hypertensive patients.

The efficacy, safety, and utility of Nigella sativa seeds oil as a complementary treatment for hypertension, glucose control, and lipid metabolism were evaluated. Hypertensive patients in the intervention (n = 26) and placebo (n = 29) groups received 2.5 ml of N. sativa seeds oil and sunflower oil twice daily for 8 weeks, respectively. The levels of systolic and diastolic blood pressure (SBP, DBP), blood lipid profile, and fasting blood sugar (FBS), at different stages of the treatment period (0, 3, 6, 8 weeks), and malondialdehyde (MDA) and glutathione reductase (GR), at the baseline and end of the study, were assessed. SBP level in the intervention group was significantly reduced, compared with the baseline values (p < .001) and the placebo group (p < .05). A significant decline was observed in the levels of DBP, total cholesterols, and low density lipoprotein (LDL) (p < .000), MDA, and FBS (p < .001); also, a significant increase was observed in the levels of high density lipoprotein (HDL) and GR (p < .001). The use of N. sativa seeds oil as an adjunct to common medications exhibited additional antihypertensive effects as well as beneficial effects on glucose control and lipid metabolism in hypertensive patients with no renal, hepatic, and patient-reported adverse events.

Structure and function of resistance arteries from BB-creatine kinase and ubiquitous Mt-creatine kinase double knockout mice.

Increasing evidence indicates that the enzyme creatine kinase (CK) is intimately involved in microvascular contractility. The mitochondrial isoenzyme catalyses phosphocreatine synthesis from ATP, while cytoplasmic CK, predominantly the BB isoenzyme in vascular tissue, is tightly bound near myosin ATPase, where it favours ATP production from phosphocreatine to metabolically support vascular contractility. However, the effect of CK gene inactivation on microvascular function is hitherto unknown. We studied functional and structural parameters of mesenteric resistance arteries isolated from 5 adult male mice lacking cytoplasmic BB-CK and ubiquitous mitochondrial CK (CK-/-) vs 6 sex/age-matched controls. Using a Mulvany Halpern myograph, we assessed the acute maximum contractile force with 125 mM K+ and 10-5 M norepinephrine, and the effect of two inhibitors, dinitrofluorobenzene, which inhibits phosphotransfer enzymes (0.1 µM), and the specific adenylate kinase inhibitor P1, P5-di(adenosine 5') pentaphosphate (10-6 to 10-5 M). WT and CK-/- did not significantly differ in media thickness, vascular elasticity parameters, or acute maximum contractile force. CK-/- arteries displayed greater reduction in contractility after dinitrofluorobenzene 38%; vs 14% in WT; and after AK inhibition, 14% vs 5.5% in WT, and displayed abnormal mitochondria, with a partial loss of the inner membrane. Thus, CK-/- mice display a surprisingly mild phenotype in vascular dysfunction. However, the mitochondrial abnormalities and greater effect of inhibitors on contractility may reflect a compromised energy metabolism. In CK-/- mice, compensatory mechanisms salvage energy metabolism, as described for other CK knock-out models.

Information Technology-Based Interventions to Improve Drug-Drug Interaction Outcomes: A Systematic Review on Features and Effects.

The purpose of this systematic review was to identify features and effects of information technology (IT)-based interventions on outcomes related to drug-drug interactions (DDI outcomes). A literature search was conducted in Medline, EMBASE, and the Cochrane Library for published English-language studies. Studies were included if a main outcome was related to DDIs, the intervention involved an IT-based system, and the study design was experimental or observational with controls. Study characteristics, including features and effects of IT-based interventions, were extracted. Nineteen studies comprising five randomized controlled trials (RCT), five non-randomized controlled trials (NRCT) and nine observational studies with controls (OWC) were included. Sixty-four percent of prescriber-directed interventions, and all non-prescriber interventions, were effective. Each of the following characteristics corresponded to groups of studies of which a majority were effective: automatic provision of recommendations within the providers' workflow, intervention at the time of decision-making, integration into other systems, and requiring the reason for not following the recommendations. Only two studies measured clinical outcomes: an RCT that showed no significant improvement and an OWC that showed improvement, but did not statistically assess the effect. Most studies that measured surrogate outcomes (e.g. potential DDIs) and other outcomes (e.g. adherence to alerts) showed improvements. IT-based interventions improve surrogate clinical outcomes and adherence to DDI alerts. However, there is lack of robust evidence about their effectiveness on clinical outcomes. It is recommended that researchers consider the identified features of effective interventions in the design of interventions and evaluate the effectiveness on DDI outcomes, particularly clinical outcomes.

Therapeutic potential of Capparis spinosa in experimental model of acute acetic acid-induced colitis: Anti-inflammatory and antioxidant effects.

Introduction: This study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. Method: Sixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. Results: The results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). Conclusion: The study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

Co-prescription of gastroprotective agents and their efficacy in elderly patients taking nonsteroidal anti-inflammatory drugs: a systematic review of observational studies.

BACKGROUND & AIMS: Guidelines recommend prescribing gastroprotective agents (proton pump inhibitors, misoprostol) to older patients (primarily ≥65 years old) taking nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent gastrointestinal ulcers. Older individuals are underrepresented in clinical trials of these agents. We systematically reviewed evidence from observational studies on the use of gastroprotective agents in elderly patients and their ability to prevent NSAID-related ulcers in this population. METHODS: We performed a systematic search of Embase and MEDLINE and identified 23 observational studies that focused on elderly patients and reported data on co-prescription of gastroprotective agents and NSAIDs and/or the effectiveness of the agents in preventing gastrointestinal events in NSAID users. We collected data on rates of co-prescription and NSAID-related gastrointestinal events in patients with and without gastroprotection. RESULTS: A median of 24% (range, 10%-69%) of elderly patients taking NSAIDs received a co-prescription for gastroprotective agents; this percentage was only slightly higher in the oldest age groups. All studies of efficacy showed a positive effect of gastroprotection. However, the adjusted results were not suitable for synthesis, and the 5 studies reporting unadjusted results were too heterogeneous for meta-analysis (I(2) = 97%). The studies differed in outcomes, definitions of co-prescription, and differences in baseline risk factors between patients with and without gastroprotection. None of the studies assessed adverse effects of gastroprotective agents. The 2 cost-effectiveness studies reached opposing conclusions. CONCLUSIONS: In a systematic review, the observational evidence for the efficacy of gastroprotective agents in preventing NSAID-associated gastrointestinal events was in agreement with results of randomized controlled trials. However, because of heterogeneity of included studies, it is not clear what the effect would be if more patients were treated, or at what age gastroprotection should be recommended. We offer suggestions to facilitate comparison with other work and address the questions of risk and benefit in relation to age.

The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice.

Aim: This study compared a topical formulation containing lytic phages with a routine antibiotic in the murine model of burn/Pseudomonas aeruginosa infected wound healing. Methods & Materials: Isolated and purified lytic bacteriophages from hospital sewage were added to the polyethylene glycol (PEG) based ointment. A second-degree burned wound on the back of twenty-four adult female mice was created. The wounds were infected subcutaneously with 100 µL of 1 × 102-3 CFU/mL P. aeruginosa. After 24 h, mice were randomly assigned to one of four groups: mice received a standard antibiotic (antibiotic-treated group), mice received an ointment without bacteriophage (PEG-based group), mice received a PEG-ointment with bacteriophage (bacteriophage-treated group), or mice received no treatment (untreated-control group). Every two days, the contraction of burned wounds, physical activity, and rectal body temperature were recorded. On day 10, mice were sacrificed, and the wounds were cut off and evaluated histopathologically. Results: In ointments containing PEG, bacteriophages were active and stable. The mice receiving bacteriophage and PEG-based ointment had substantially different wound contraction in primary wound healing (P = 0.001). When compared to the control group, the bacteriophage-treated group showed significant variations in wound contraction (P = 0.001). The wound contraction changed significantly between the antibiotic and PEG-based groups (P = 0.002). In all groups, physical activity in mice improved over time, with significant differences (P = 0.001). When the 8th day was compared to the days 2, 4, and 6, significant changes were found (P = 0.001, P = 0.02, and P = 0.02, respectively). Both the positive control and bacteriophage-treated groups showed perfect wound healing histopathologically. However, no significant variations in microscopic histopathological criteria were found between the groups. Conclusion: Formulated phage ointment could be a promising approach for treating infected burn wounds infected by P. aeruginosa in mice with no allergic reactions.

Antibiotic prescribing in inpatient and outpatient settings in Iran: a systematic review and meta-analysis study.

BACKGROUND: Antibiotic prescribing is common worldwide. There are several original studies about antibiotic prescribing in the healthcare setting of Iran reporting different levels of prescribing. The aim of this systematic review and meta-analysis was to determine the prevalence of antibiotic prescribing in both inpatient and outpatient settings in Iran, an example of a developing country. METHODS: To identify published studies on antibiotic prescribing, databases such as ISI, Scopus, PubMed, Google Scholar, and Electronic Persian were searched in Iran till January 2020. Eligible studies were those analyzing original data on the prescription and use of antibiotics in outpatient or inpatient settings in Iran. Moreover, all studies that used an intervention to improve antibiotic prescribing were included. The quality of the included studies was assessed using self-administered quality assessment criteria. The meta-analysis of prevalence of antibiotic prescribing was conducted based on the meta-analysis of observational studies in epidemiology guidelines. To calculate pooled rates, the random-effects model was used. RESULTS: A total of 54 studies (39 outpatients and 15 inpatients) were included in this study. The median of antibiotic prescribing in the outpatient and inpatient settings accounted for 45.25% and 68.2% of patients, respectively. The results of meta-analysis also showed that the antibiotic prescribing accounted for 45% of prescriptions in outpatient settings and 39.5%, 66%, and 75.3% of patients in all wards, pediatrics wards, and ICU wards of inpatient settings, respectively. The most commonly prescribed antibiotic classes in outpatient settings were penicillins, cephalosporins, and macrolides, while in inpatient settings, these were cephalosporins, penicillins, and carbapenems. There were seven studies using interventions to improve antibiotic prescribing pattern. It should be mentioned that intervention in a study had a statistically significant effect on improving antibiotic prescribing (p < .05). CONCLUSION: Prevalence of antibiotic prescribing in Iran is high. Our findings highlight the need for urgent action to improve prescription practices. It seems that developing a national plan to improve antibiotic prescribing is necessary.

Postprandial effects of macronutrient composition meals on the metabolic responses and arterial stiffness indices of lean and obese male adults: a protocol of a pilot study.

BACKGROUND: Prior studies have shown that meal composition may affect the metabolic responses and arterial stiffness indices, and these responses may be different in lean and obese adults. The primary objective of this study is to determine the feasibility of conducting a trial to compare the effect of three test meals in lean and obese men. Due to the lack of a comprehensive study that concurrently compares metabolic responses and vascular stiffness indices after receiving three different meals in lean and obese men, this pilot study will be conducted with a three-phase parallel design, aiming to investigate the effects of meal composition on the metabolic parameters and arterial stiffness indices of lean and obese adults. METHODS: This pilot, a parallel clinical trial will be performed on 24 male adults aged 18-35 years since January 2021 and will continue until March 2021 who are disease-free and selected based on the inclusion and exclusion criteria at Mashhad University of Medical Sciences, Iran. The subjects will complete three interventions at a 1-week interval, including high carbohydrate (70% carbohydrates, 10% protein, 20% fat), high protein (30% protein, 50% carbohydrates, 20% fat), and high-fat meal (50% fat, 40% carbohydrates, 10% protein). Postprandial effects will be assessed within 360 min after each meal, including the energy expenditure component (resting energy expenditure, thermic effects of feeding, respiratory quotient, and substrate oxidation) and arterial stiffness indices (augmentation index and pulse wave velocity). In addition, blood sampling will be performed to measure glucose, insulin, free fatty acids, and lipid profile. DISCUSSION: The differences in the postprandial responses can affect the metabolic and vascular parameters due to different meal compositions, thereby providing beneficial data for the establishment of new strategies in terms of nutritional education and metabolic/vascular improvement. Also, the results from this pilot study will inform intervention refinement and efficacy testing of the intervention in a larger randomized controlled trial. TRIAL REGISTRATION: Iranian Registry of Clinical Trials; code: IRCT20190818044552N1 ; registered on August 26, 2019.

Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats.

This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-ß, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.

Evaluation of wound healing efficiency of vancomycin-loaded electrospun chitosan/poly ethylene oxide nanofibers in full thickness wound model of rat.

Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent.

Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin, a natural polyphenolic compound, is proposed as a potential treatment option for patients with coronavirus disease by inhibiting the entry of virus to the cell, encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. In this study, the efficacy and safety of nanocurcumin oral formulation has been evaluated in patients with mild-moderate Coronavirus disease 2019 (COVID-19) in outpatient setting. METHODS: In this triple-blind randomized placebo-controlled clinical trial, sixty mild to moderate COVID-19 patients in outpatient setting who fulfilled the inclusion criteria were randomly allocated to treatment (n = 30) group to receive oral nanocurcumin formulation (Sinacurcumin soft gel which contains 40 mg curcuminoids as nanomicelles), two soft gels twice a day after food for 2 weeks or placebo (n = 30) group. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period and compared between two groups. RESULTS: All symptoms except sore throat resolved faster in the treatment group and the difference was significant for chills, cough and smell and taste disturbances. The CRP serum level was lower in the treatment group at the end of two weeks and the lymphocyte count was significantly higher in treatment group. No significant adverse reaction reported in the treatment group. CONCLUSION: Oral nanoformulation of curcumin can significantly improve recovery time in patients with mild to moderate COVID-19 in outpatient setting. Further studies with larger sample size are recommended.

Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex.

Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture (number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with l-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop l-NAME-induced hypertension in mice.

Evaluation of sedative effects of an intranasal dosage form containing saffron, lettuce seeds and sweet violet in primary chronic insomnia: A randomized, double-dummy, double-blind placebo controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Persian Medicine (TPM) has been established as a valuable source of medicinal plants for the treatment of insomnia for thousands of years. Accordingly, oil extracts from plants' parts have been widely used to alleviate central nervous system (CNS) ailments including sleep disorders. A number of preparations have been recommended by TPM for the treatment of insomnia. Among them, an intranasal formulation containing oily macerates of Viola odorata L., Crocus sativus L. and Lactuca sativa L. stands out. AIM OF THE STUDY: In the present double-dummy, double-blind placebo controlled clinical trial, we aim to evaluate the effectiveness of a combination of violet oil, saffron oil, and lettuce seeds oil nasal drop compared with the placebo (sesame oil). MATERIALS AND METHODS: Fifty patients with primary chronic insomnia were randomly assigned in TPM-treatment or placebo groups, received either two drops of the herbal oil or placebo into each nostril every noon and evening for 8 weeks. Before the study commencement and after 1, 4 and 8 weeks of treatment, Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires were completed by all patients. The primary outcome measure was considered as any changes in ISI scores between the first visit and after 8 weeks. Changes in PSQI scores during the study and possible side effects were also assessed. The multicompound herbal oil was standardized using HPLC analysis and contained 0.02 mg/mL crocin and 4 µg/mL isoquercitrin. RESULTS: Our study revealed a significant reduction in the ISI and PSQI scores from baseline by the study endpoint (P ≤ 0.01). The mean ISI scores in week 8 decreased significantly for the intervention group (P = 0.001) and also the placebo group (P < 0.01) when compared with baseline. Moreover, the use of hypnotic drugs in the intervention group was significantly reduced (P < 0.001), while in the control group was maintained at baseline level. CONCLUSIONS: It seems that intranasal use of the multi-herbal preparation can be used to improve chronic insomnia and to reduce the dose of conventional hypnotic medications in insomniac patients.

Effect and features of information technology-based interventions on self-management in adolescent and young adult kidney transplant recipients: a systematic review.

INTRODUCTION: Adolescent and young adult periods are characterized by increased risk-taking, impulsive behavior, and nonadherence issues, which makes it equally challenging for patients and their health care professionals. Health information technology (IT) has the potential to empower patients. OBJECTIVE: Determine the effects and features of IT-based interventions for self-management of adolescents and young adults in kidney transplant recipients. MATERIALS AND METHODS: A comprehensive survey was done on Medline and Scopus in September 2018. Eligible studies included randomized controlled trials (RCTs) and quasi-experimental studies focused on automated IT-based interventions. Studies contained information about adolescent and young adult kidney transplant recipients aged under 25, all published in English. The articles were combined with each other based on the classification of outcomes, the type of interventions, and their impact. The studies were categorized based on the impact of interventions as positive and statistically significant, with no effect, or a combined effect (both positive significance and without effect). RESULTS: In this review, of a total of 2,242 retrieved articles, collected from Scopus and PubMed databases, 5 studies met the full-text inclusion criteria. Interventions were performed using computerized systems (3 studies), smartphone application/personal digital ass (PDA) (1 study), and multiple components (1 study). These studies evaluated 15 outcomes, including 7 care process and 8 clinical outcomes. In 6 of 15 outcomes (40%), interventions had a statistically significant positive effect. CONCLUSION: IT-based interventions such as mobile health/personal digital assistant(PDA), computer systems and multi-component have the potential to improve self-management in adolescents and young adult kidney transplant recipients (care process outcomes). It is recommended to conduct complementary research to examine the effect of IT-based self-management interventions on clinical outcomes in kidney transplant recipients.

Factors Associated With Adherence To Immunosuppressive Therapy And Barriers In Asian Kidney Transplant Recipients.

BACKGROUND: Medication non-adherence is the major risk factor for rejection episodes. The aim of this study was to determine the risk factors associated with adherence to immunosuppressive regimen and its barriers among kidney transplant (KT) recipients. METHODS: A cross-sectional study was performed in two outpatient post-transplant clinics in Mashhad, northeast of Iran. All patients who attended the clinics from August to October 2017 were included. Patients's knowledge, adherence to immunosuppressive regimen, and quality of life were measured using the Kidney Transplant Understanding Tool, Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), and SF-12V2 questionnaire, respectively. The barriers in adhering immunosuppressive regimen were investigated by Immunosuppressive Therapy Barriers Scale. Logistic regression was used to screen the significant risk factors of medication non-adherence. RESULTS: In this study, 244 KT recipients were included with a mean age of 39.6±12.5 years. Based on the BAASIS score, 111 (45.5%) patients were adherent to immunosuppressive regimen. Female patients were more likely to be adherent (OR=0.48, p<0.01). The patients with higher level of quality of life were more likely to follow immunosuppressive medications (OR=1.078, p<0.05). The main barriers were as follows: concurrent use of many immunosuppressants, lack of knowledge about the usefulness of immunosuppressive medications, confusion in medication taking, and difficulty in remembering medication taking. CONCLUSION: More than half of the KT recipients were non-adherence to immunosuppressive regimen. These findings highlight the need for designing interventions in order to reduce or eliminate these barriers and consequently increase medication adherence among KT recipients.

Effect of an interactive voice response system on self-management in kidney transplant recipients: Protocol for a randomized controlled trial.

INTRODUCTION: Adherence to a complex and ongoing set of therapeutic recommendations significantly determines short and long-term outcomes after kidney transplantation (KT). Interactive voice response system (IVRS) is a novel phone-based platform which is potentially useful to deliver health behavior interventions. OBJECTIVE: The aims of the study is to describe the development of a theory-driven and educational IVRS investigate the effect of an IVRS on the self-management outcomes in KT recipients as compared with the control group. METHODS: This study has been designed as a randomized, 2 parallel groups controlled trial. The KT recipients' older than18 years of age with access to a cellphone will be included. A total of 120 patients will be randomly assigned to the control and intervention groups. The participants in the intervention group will receive completely automatic calls in 3 categories: educational, medication adherence, and reminders by the IVRS, whereas those in the control group will receive usual care. The follow up will be performed within 6 months. The primary outcome will be the medication adherence while patients' transplant knowledge, health-related quality of life, and rehospitalization rates will be considered as secondary outcomes. RESULTS: Thus far, recruitment of participants has not been completed and results will be published in 2019. DISCUSSION: The IVRS is potentially useful to help KT recipients improve the self-management outcomes. The hypothesis is using an IVRS intervention makes a significant difference between basel assessment of adherence to immunosuppressive medications scale, 12-item short form survey, second version, kidney transplant understanding tool baseline scores, and those obtained at the end of study. TRIAL REGISTRATION NUMBER: This trial is registered with the Iran Trial Registrar under registration number IRCT20180124038492N1 and registration date 30 January 2018. https://irct.ir/trial/29215.