Epidemiology of Completed Suicides Referred to Forensic Pathology Organization of Tehran, Iran, During March 2011 to March 2016

Background: Completed or successful suicide is the worst outcome of suicide attempts. This study is an epidemiologic investigation of successful suicides in Tehran, Iran.Methods: In this routine-data-based study, the records of successful suicides in Forensic Pathology Organization of Tehran were investigated with respect to confidentiality of information during March 2011 to March 2016. The obtained data were analyzed by SPSS 11.5. Statistically significant level was considered at less than 0.05.Results: A total of 1773 cases with mean (SD) age of 33.19(13.11) years and male-to-female ratio of 3.1 were included in the study. The mean age of male victims was greater than that of female ones (P=0.01). Of victims, 821(46.3%) were single and 807(45.5%) were unemployed/housewife. Methods of suicide were hanging in 962(54.6%), poisoning in 640(35.8%), falling in 88(5%), burning in 35(2%), shooting in 29(1.6%) and others in 19(1%) cases. Of poisoned cases, 283(44%) were victims of aluminum phosphide ingestion. Generally, frequency of married victims was greater than single ones but by comparing genders, relative frequency of single victims was greater among males (P<0.001). There was statistically significant association between suicide methods and age (P=0.001), gender (P<0.001), and occupation (P<0.001) of victims. Among different methods, shooting and poisoning were used by the youngest cases. Relative frequency of females was greatest in victims of burning and poisoning. Regarding occupational categories, poisoning was most frequent in students.Conclusion: In this study, the majority of successful suicides happened in people with occupational uncertainty, thus preventive measures should prioritize this issue. It seems that women with marital problems are also prone to suicide and social support programs should target this group, too. Association between the method of suicide and demography of victims will help us to recognize common methods in various groups of the society and establish appropriate preventive measures. While limiting access to supplies of suicide (like legislation on distribution of drugs for prevention of poisoning) is valuable, fundamental interventions at community level will be more effective in prevention of all kinds of suicide

Research Paper: Patterns of Drunk and Drugged Driving in Fatally Injured Drivers in Tehran, Iran

Background: Substance abuse in drivers is a global public health concern. We investigated patterns of alcohol and illicit drug consumption in drivers died in traffic accidents in Tehran Province, Iran.Methods: In this cross-sectional study, presence of alcohol and illicit drugs in the body of dead drivers referred to Tehran Legal Medicine Organization during April 2016 to April 2018 were investigated. All participants underwent autopsy and their urine, visceral and vitreous samples were examined for alcohol and illicit drugs. Victims with Complete Toxicology Tests for both alcohol and non-alcoholic drugs and those autopsied during their first 24 hours of death were included. Victims’ demographic characteristics, results of their toxicology tests and accident-related factors were investigated, too. To warrant confidentiality of information, identities of victims were concealed. The obtained data were analyzed by SPSS V. 16 and statistically significant level was set at less than 0.05. Results: Of 618 study participants (mean age of 36.95 years), 601 (97.3%) were male. Of victims, 566 (91.3%) were city inhabitants and 471 (76.2%) were with educational attainment of lower than high school. The majority (93%) of crashes happened inside the city. Causes of death were head trauma in 519 (84%) cases, multiple traumas in 62 (10%) cases and bleeding in 37 (6%) cases. Multiple and single-vehicle accidents account for 498 (80.5%) and 98 (17.5%) crashes, respectively. A total of 73 (11.8%) cases were found positive for alcohol/drug consumption: 24 (4%) were alcohol positive, 52 (8.4%) were positive for non-alcoholic drugs (3 were positive for both). Main detected non-alcoholic drugs were morphine and tramadol. There was statistically significant association between drug/alcohol consumption of drivers and cause of death and crash mechanism (Both P<0.001). Multiple traumas and single vehicle crashes were more prevalent among drivers with drug/alcohol positive tests.Conclusion: Rate of alcohol use in our drivers was lower than many countries which is attributed to religious and legal issues. Consistent with the reported pattern of drug abuse in Iranian general population, opioids and tramadol were the main drugs of abuse among studied drivers. Drug or alcohol use result in drivers’ distraction and more fatal injuries

Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages

Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epi-dermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheri-tance. The mutation profile attests to the impact of consanguinity in these families

Recent advances in improving oral drug bioavailability by cocrystals

Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human

Gene-Targeted Next Generation Sequencing Identifies PNPLA1 Mutations in Patients with a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The Impact of Consanguinity

Heritable forms of ichthyoses, also referred to as generalized Mendelian disorders of cornification, are phenotypically a highly heterogeneous group of conditions caused by mutations in a number of genes playing a role in keratinocyte differentiation and epidermal barrier function (Baden and Digiovanna, 2013; Schmuth et al., 2013). These diseases are characterized by scaling and hyperkeratosis with associated cutaneous and extracutaneous features. This group of disorders is also genetically heterogeneous, with autosomal dominant, autosomal recessive, and X-linked inheritance being described. A specific subgroup of inherited ichthyoses is the autosomal recessive congenital ichthyosis (ARCI), with many newborns presenting as collodion babies, but the subsequent clinical presentation and the spectrum of severity can be highly variable (Richard and Bale, 2014). In the most severe forms, such as harlequin ichthyosis, the disease is often fatal during the early postnatal period, whereas at the other end of the continuum of the spectrum, the disease may present with a relatively mild scaling and variable degree of palmoplantar keratoderma. There is considerable genetic heterogeneity in ARCI, and as many as nine different genes are known to harbor biallelic mutations; these include TGM1, ALOXE3, ALOX12B, NIPAL4, ABCA12, CYP4F22, PNPLA1, LIPN, and CERS3. Previous reports have suggested that mutations in TGM1 account for 30e65% of patients with ARCI, whereas mutations in LIPN, PNPLA1, and CERS3 have been reported only in a few consanguineous families (Richard and Bale, 2014). With the advent of next generation sequencing (NGS), there has been tremendous progress in facilitating the mutation detection in various heritable skin disorders, including ichthyosis (South et al., 2015; Takeichi et al., 2013). In fact, at least 38 different genes have now been suggested to be associated with the ichthyotic phenotypes, either as the primary mutated genes or modifying the phenotypic presentation. To elucidate the genetic basis of ichthyosis in Iran, a country of approximately 80 million people with high prevalence of customary consanguineous marriages, we developed a gene-targeted NGS array consisting of 38 genes reported in association with ichthyosis phenotypes. Identification of specific mutations in a large number of families has allowed us to examine phenotype/genotype correlations with respect to both intra- and interfamilial heterogeneity, in part because of extensive consanguinity in these families. In this study, we identified six distinct and, to our knowledge, previously unreported mutations in the PNPLA1 gene in nine families

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD), particle size analyzer and differential scanning calorimetry (DSC). Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR) spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models

Studying of prosodic structure in Persian Odes

Abstract This study is a research about rhythms and poetical works which are used in Persian literature odes in of forth century up to now. Firstly, this research, 50 odes of the poetical works of celebrated poets are considered in all periods of Persian literature and the types of rhythm and contents which they are interested in are specified that the results of this research formed the following assay.  In this article 1632 odes are considered, it observed that most common poetical works in Persian language is considered by the writers of odes and they have composed long poems in these rhythms. Also from the viewpoint of content in the primary centuries of Persian poems, the poets paid attention to the contents of Arabic poets but the new contents gradually entered the Persian literature by the growth of odes in Persian literature which will be referred to nex