On the Stereochemistry of the NH Bond Activation of Ammonia or Amines by Disilenes: Predictability.

The stereochemistry of the addition of NH3 to the stereoisomers of 1,2-di-tert-butyl-1,2-bis(2,4,6-triisopropylphenyl)disilene (Z-5 or E-5) is 100 % stereospecific giving two isomeric disilylamines 6 and 7, respectively, derived from syn-addition to the stereoisomeric disilenes. Variable time normalization analysis studies of the reaction of tetramesityldisilene (3) with isopropylamine (i PrNH2 ) revealed that the order in both amine and disilene is 1. The kinetic isotope effect for the addition of i PrNH2 /i PrND2 to tetramesityldisilene was determined to be 3.04±0.06 at 298 K, a primary KIE, indicating that the proton is transferred in the rate determining step. Competition studies between the addition of PrNH2 and i PrNH2 to tetramesityldisilene resulted in the exclusive formation of the PrNH2 adduct consistent with a nucleophilic addition. Computational studies of the mechanism of the addition of ammonia to E-5 revealed the lowest energy pathway involves the formation of the donor adduct derived from syn-addition, followed by intramolecular syn-transfer of the proton. The formation of the donor adduct is the rate determining step. The results of this study, together with previous studies on the addition of ammonia and amines to disilenes, allow for a refinement of our understanding of the mechanism of this important fundamental reaction in disilene chemistry, and allow us to understand our ability to reliably predict the stereochemical outcomes of future NH σ-bond activation reactions.

The cost of dispensing errors in Iranian health system: a retrospective evaluation.

OBJECTIVE: The problem of medication errors (MEs) has constantly been receiving considerable attention worldwide due to their health impact and costly consequences. MEs occur in all phases of prescription, preparation, administration, distribution and delivery to the patient; however, dispensing errors are more common in this study, we have attempted to identify various MEs that occurred by pharmacists and calculate their financial and physical harm costs. DESIGN: This was a 8-year retrospective study. SETTING: This study evaluated the costs of MEs in the Iranian health system caused by dispensing mistakes from 2012 to 2019. We retrieved documents and reports from the Tehran Medical Council Archive. Then, we extracted dispensing error data from ME record forms and analyzed them using SPSS software. MAIN OUTCOME MEASURES: Cost of dispensing errors. RESULTS: Among 3000 available MEs documents, only 2.6% of cases were dispensing errors. Errors included dispensing of wrong medication (75.6%), delivering expired medicines (11.5%), wrong medication order (9%), wrong medicine compounding (2.6%) and wrong dose of medication (1.3%). The most common cause of dispensing errors was physicians' poor handwriting (23.1%). Legal reactions, due to MEs, occurred in a range of actions from written reprimand in the professional records to some months of deprivation from professional activities. CONCLUSION: The analysis of the MEs that lead to the legal prosecution in the Iranian Medical Council shows that most cases, according to the severity of harm, were dispensing wrong medicines which caused temporary patients harm.

Irrational use of antibiotics in Iran from the perspective of complex adaptive systems: redefining the challenge.

BACKGROUND: Irrational use of antibiotics is proving to be a major concern to the health systems globally. This results in antibiotics resistance and increases health care costs. In Iran, despite many years of research, appreciable efforts, and policymaking to avoid irrational use of antibiotics, yet indicators show suboptimal use of antibiotics, pointing to an urgent need for adopting alternative approaches to further understand the problem and to offer new solutions. Applying the Complex Adaptive Systems (CAS) theory, to explore and research health systems and their challenges has become popular. Therefore, this study aimed to better understand the complexity of the irrational use of antibiotics in Iran and to propose potential solutions. METHOD: This research utilized a CAS observatory tool to qualitatively collect and analyse data. Twenty interviews and two Focus Group discussions were conducted. The data was enriched with policy document reviews to fully understand the system. MAXQDA software was used to organize and analyze the data. RESULT: We could identify several diverse and heterogeneous, yet highly interdependent agents operating at different levels in the antibiotics use system in Iran. The network structure and its adaptive emergent behavior, information flow, governing rules, feedback and values of the system, and the way they interact were identified. The findings described antibiotics use as emergent behavior that is formed by an interplay of many factors and agents over time. According to this study, insufficient and ineffective interaction and information flow regarding antibiotics between agents are among key causes of irrational antibiotics use in Iran. Results showed that effective rules to minimize irrational use of antibiotics are missing or can be easily disobeyed. The gaps and weaknesses of the system which need redesigning or modification were recognized as well. CONCLUSION: The study suggests re-engineering the system by implementing several system-level changes including establishing strong, timely, and effective interactions between identified stakeholders, which facilitate information flow and provision of on-time feedback, and create win-win rules in a participatory manner with stakeholders and the distributed control system.

Economic Evaluations of Anti-obesity Interventions in Obese Adults: An Umbrella Review.

This umbrella review amalgamates the outcomes of economic evaluations pertaining to bariatric surgeries, pharmacotherapy, and gastric balloon for adult obesity treatment. Six databases were systematically searched. The inclusion criteria were established following the Patient/population Intervention Comparison and Outcomes (PICO) statement. Fifteen reviews met all the inclusion criteria. Eight studies focused on surgical interventions, four on pharmacotherapy, and three on both interventions. No systematic review of the economic evaluation of gastric balloons was identified. The majority of reviews advocated bariatric surgery as a cost-effective approach; however, there was discordance in the interpretation of pharmacological cost-effectiveness. Most of the economic evaluations were conducted from the payer and the healthcare system perspectives. We propose that future economic evaluations assessing weight loss interventions in adults adopt a societal perspective and longer-term time horizons.

Exploring health seeking behaviors for common cold management.

Background: The prevalence of common cold can impose financial burden on the healthcare systems, despite its simple and self-limiting symptoms. Objective: This study examines the behavior of patients suffering from symptoms of the common cold and explores the factors that may influence such behaviors. Methods: A descriptive-analytic cross-sectional study was conducted in 2019, in Tehran, Iran, using cluster sampling in socioeconomically diverse areas within the city. The participants' behaviors and related factors were evaluated using a 10-item questionnaire. Data collection process involved selecting 5 shopping centers and 404 individuals participated the study. SPSS version 24 was used for analysis. Results: The results showed that 42.1% of the respondents would consult a physician immediately upon experiencing cold symptoms, while 11.4% would consult a pharmacist.In addition, 14.3% would try self-medication, 28.3% relied on traditional home remedies, and 15%indicated not to make use of any remedies or interventions. The study indicated a correlation between people's behaviors concerning the common cold and their level of health self-confidence, knowledge of the common cold, lifestyle, gender, marital status, occupational status, insurance status, and average family spending. Conclusion: The findings of this study are significant in that they shed light on the behaviors of individuals and associated factors related to seeking medical assistance for the common cold. This knowledge can assist healthcare systems in developing strategies aimed at enhancing treatment outcomes, and decreasing costs.

Working in hospitals during a pandemic: investigating the resilience among medical staff during COVID-19 outbreak through qualitative and quantitative research.

BACKGROUND: Medical staff in hospitals were faced with great stress as a result of COVID-19's sudden and severe occurrence, which makes investigating their resilience essential. AIMS AND METHODS: Using qualitative and quantitative research methods, this research studied medical staff (n = 403) working in a hospital during the COVID-19 pandemic and followed four main goals: First was evaluating the psychometric properties of the Persian version of Adult Resilience Measure-Revised (ARM-R). The second goal was investigating the personal, relational, social, and organizational issues facing the medical staff during the COVID-19 using semi-structural interviews. The third goal was to determine predictive effects of demographic and work-related variables on resilience using stepwise regression analysis. And the fourth was comparing resilience of three groups of the medical staff (coronavirus group consisted of the medical staff in direct contact with COVID-19 patients; emergency group who work in the emergency department who deal with both COVID and non-COVID patients; and non-coronavirus group who had no contact with COVID-19 patients) using one-way ANOVA. FINDINGS: Results showed that internal reliability/consistency, content, and face validity of the Persian version of the ARM-R are acceptable. The construct validity of the test was also verified using exploratory factor analysis and indicated the two factors of personal and relational resilience. The content of the interviews was analyzed using manifest content analysis, and the results were divided into 27 subcategories and 3 main categories including personal, organizational, and family categories. Moreover, regression analysis revealed that the marital status and age of children can explain resilience variance in some medical staff groups. The results of ANOVA and post hoc test also showed that the total resilience of the non-coronavirus group was greater than the coronavirus and emergency groups; the relational resilience of the coronavirus and non-coronavirus groups was greater than the emergency, and non-coronavirus group's personal resilience was greater than the emergency group.

An investigation into the pharmaceutical advertising in Iranian medical journals.

BACKGROUND: Pharmaceutical advertising is not only considered a key factor in the successful launch of pharmaceutical products, but is also an important source of public health information with a significant impact on consumer choice and behavior. Nowadays, advertising has become the broadest dissemination channel for various products, including medicines, which may ultimately lead to the generalization of self-treatment or mistreatment. Improper drug promotion can exacerbate unhealthy outcomes by making false or misleading claims, using inferior references, and failing to meet international standards. This study aimed to examine the requirements for pharmaceutical advertising from regulatory perspective and the compliance of Iranian pharmaceutical advertisements to related standards and guidelines. It is limited to print advertisements in Iranian national medical journals and magazines. METHOD: The present study is a descriptive-analytical study using bibliometric methods. As a first step, a comprehensive review of the national and international regulations on drug advertising was conducted and a comparison of different regulations was provided. In the second step, a checklist was created to evaluate the compliance of drug advertising with the extracted regulations. RESULT: The results of the present study show that the claims made in Iranian drug advertisements are 29.10% valid, 27.67% exaggerated, 23.10% controversial, 12.62% misleading, and 6.8% invalid. In general, we found that most medical advertisements in Iranian journals and magazines comply with national laws and regulations. However, many international requirements are not met in these advertisements. CONCLUSIONS: Although we found that printed medical advertisements in Iran are roughly compliant with national regulations, there is still a long way to achieve full compliance. Monitoring processes should be improved and clearly defined penalties should be set to avoid misleading claims and their likely health consequences. It is very important in Iran to update the existing rules and regulations for medical advertisements according to international guidelines. More careful monitoring of the content of advertising and the accuracy of claims are also needed.

Changing parenting style between two generations and its impacts on the severity of behavioral and emotional symptoms.

OBJECTIVE: The purpose of this study is to compare the perceived parenting dimensions in mothers and their daughters (differences between two generations), and study the relationship between these dimensions and the severity of daughters' behavioral and emotional symptoms. MATERIALS AND METHODS: 300 participants (150 daughters with their mothers) participated in this study. They responded to the perceived parenting styles questionnaire (PSQ), and mothers were additionally asked to answer the child symptoms inventory-4 (CSI-4). Data analysis was done by the SPSS using the paired sample t-test and multiple regressions. RESULTS: The results indicated a significant difference between perceived parenting dimensions in mothers and their daughters; specifically, acceptance and control dimensions increased through generation. It was also found that daughters' acceptance-rejection dimension could predict the severity of the symptoms of attention-deficit/hyperactivity disorders, autism spectrum disorders, depression, dysthymia, conduct disorders, and opposite defiant disorders. The control-autonomy dimension could also predict the severity of schizophrenia symptoms. CONCLUSION: The results indicate the different parenting styles between two generations and the critical role of parenting in developing the children's psychopathology symptoms.

Ex vivo generation of a highly potent population of circulating angiogenic cells using a collagen matrix.

Biomaterials that have the ability to augment angiogenesis are highly sought-after for applications in regenerative medicine, particularly for revascularization of ischemic and infarcted tissue. We evaluated the culture of human circulating angiogenic cells (CAC) on collagen type I-based matrices, and compared this to traditional selective-adhesion cultures on fibronectin. Culture on a collagen matrix supported the proliferation of CD133(+) and CD34(+)CD133(+) CACs. When subjected to serum starvation, the matrix conferred a resistance to cell death for CD34(+) and CD133(+) progenitors and increased phosphorylation of Akt. After 4days of culture, phenotypically enriched populations of endothelial cells (CD31(+)CD144(+)) and progenitor cells (CD34(+)CD133(+)) emerged. Culture on matrix upregulated the phosphorylation and activation of ERK1/2 pathway members, and matrix-cultured cells also had an enhanced functional capacity for adhesion and invasion. These functional improvements were abrogated when cultured in the presence of ERK inhibitors. The formation of vessel-like structures in an angiogenesis assay was augmented with matrix-cultured cells, which were also more likely to physically associate with such structures compared to CACs taken from culture on fibronectin. In vivo, treatment with matrix-cultured cells increased the size and density of arterioles, and was superior at restoring perfusion in a mouse model of hindlimb ischemia, compared to fibronectin-cultured cell treatment. This work suggests that a collagen-based matrix, as a novel substrate for CAC culture, possesses the ability to enrich endothelial and angiogenic populations and lead to clinically relevant functional enhancements.

How Much Iranian Parents Know of and How Well They Practice Regarding Antibiotics?

Irrational use of antibiotics as a global health concern has led to excessive treatment costs, failure of treatments, and antimicrobial resistance. Parents' knowledge of and practice regarding antibiotics are two important factors contributing to the (ir) rational use of antibiotics. This study aimed to evaluate ill children's parents' knowledge and practice of prescribed antibiotics. Our subjects included only parents with children up to 12 (inclusive) years of age in Tehran, Iran's capital. A prospective cross-sectional survey was conducted at 203 health care centers in Tehran. Parents' knowledge was evaluated using a 37-item researcher-made questionnaire, and their practice about antibiotics was measured with a self-stated questionnaire, followed by an observational method to gain a real insight into their practice. SPSS 22 was used to analyze the data. A total of 401 randomly selected parents were enrolled in the study. The average score of parents' knowledge of antibiotics regarding administration, indications, storage, and antimicrobial resistance was found to be 9.72 out of 17.00. In the self-stated method, an appropriate practice of antibiotic use was reported in 49.4% of participants who also got an average score of 3.95 points out of a total 8. In the observational method, most parents' practice (68.4%) regarding antibiotic use was found to be acceptable; their average score was 5.93 points out of a total of 10. The findings of this study showed that half of the parents had adopted an acceptable practice regarding antibiotic use.

Providing a framework for assessment of the access to medicine.

OBJECTIVE: Improving access to effective and safe medicines is one of the major goals of all health systems. To achieve this goal, assessment is a fundamental phase of national medicine programs for access improvement. Collecting and compiling applicable indicators and impart a comprehensive framework for assessing access to medicine, are the aims of this study. METHODS: To investigate the published materials on access to medicines framework or indicators, a literature review with a systematic search was conducted using PubMed/ Medline, Scopus, and Google Scholar databases. The results were completed with a general search of documents in Iran Food and Drug Administration (IRFDA). Two independent researchers reviewed all the articles and documents. Thereafter the related indicators were extracted. In focused group discussion of academics and IRFDA experts, duplicate entries or ineffectual concepts were cleaned from the preliminary indicators. In the next step, Delphi questionnaire was sent to the 17 experts that work in academia, Social Security Insurance, IRFDA, Ministry of Health and Iran Pharmacist Association. The results of Delphi technique were finalized in an expert panel. RESULTS: One hundred and thirty one indicators were found in systematic search. After primary extraction of related indicators, 77 indicators were sent to the 17 experts in a Delphi form. The results of Delphi were finalized in a specialized-working group and 67 indicators were accepted in 5 categories including physical availability and geographical accessibility (19 indicators), affordability (23 indicators), human resources (4 indicators), quality and safety (5 indicators), information and rational use (16 indicators). CONCLUSION: The indicators that inclusively assess the full access to medicine in the concept of rational use have been categorized into five categories in this study. To determine the access to medicine status in each country further local surveys are necessary for all several indicators in each category. Graphical abstract The graphical abstract of accomplished steps.

The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats.

 Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with L-NAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats.

The use of pharmaceutical care to improve health-related quality of life in hemodialysis patients in Iran.

BACKGROUND: Compared with the general population, hemodialysis patients suffer from worse health-related quality of life (HRQoL). Poor HRQoL results in the higher risk of hospitalization and mortality. OBJECTIVE: This study was designed to assess the impact of pharmaceutical care on HRQoL of hemodialysis patients. SETTING: This study was performed in a university hemodialysis center in Iran. METHODS: At the initiation of the study HRQoL of dialysis patients were assessed using SF-36 instrument and patients' demographic and laboratory data were gathered. Hemodialysis patients were randomized to receive either only standard care of the ward consisted of brief medication review by nurses and monthly visits by nephrology fellow and attending physicians as the control group or receive clinical pharmacist-led pharmaceutical care in addition to the standard care of the ward as the case group. Finally patients' HRQoL were assessed at the end of the month six of the study in both groups. MAIN OUTCOME MEASURE: Quality of life as measured with the SF-36 was compared between case and control groups and within each group at the initiation and at the end of 6 months study. RESULTS: During this study, median (IQR) of HRQoL improved significantly from 56.9 (37.7-71.7) at the initiation of the study to 72.2 (55.3-83.7) at the end of the study in the case group (P = 0.001) especially in the role-emotional [from 66.6 (33.3-66.6) to 100.0 (100.0-100.0); P = 0.001], mental health [from 54.2 (40.8-73.5) to 68.3 (58.9-90.2); P = 0.007], social functioning [from 73.6 (37.5-100.0) to 93.4 (75.0-100.0); P = 0.01], and general health [from 45.0 (30.0-70.0) to 65.0 (48.8-75.0); P = 0.001] dimensions. Conversely, HRQoL did not change or decreased in the control group. This decrease was statistically significant in the general health domain [from 47.5 (33.8-56.3) to 40.0 (23.7-51.2); P = 0.04]. CONCLUSION: Providing pharmaceutical care significantly improved HRQoL of hemodialysis patients especially in the role-emotional, mental health, social functioning, and general health dimensions.

Kallikreins 5, 6 and 10 differentially alter pathophysiology and overall survival in an ovarian cancer xenograft model.

Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer.