Multidisciplinary approach to functional somatic syndromes:study protocol for a population-based prospective cohort study

Introduction Isfahan functional disorders (ISFUN) cohort study aims to describe the interplay of genetic and environmental factors in shaping the characteristics of functional somatic syndromes (FSS). This study is primarily intended to investigate the epidemiology, risk factors, course and prognosis of FSSs in a sample of adult Iranian population. The other aim is to develop a new delimitation of FSSs based on an integrated multidisciplinary approach comprising of phenotypic and multiomics data. Methods and analysis ISFUN is a population-based prospective cohort study designed to follow a population of randomly selected seemingly healthy adults (18-65 years) through annual visits during a 4-year observation period. Structured questionnaires are used for data collection and clinical assessment of the participants. Questionnaire-based diagnosis of FSSs are validated in a medical interview. Human DNA genotyping, microbial amplicon sequencing and urine analysis is under progress for genomics, microbiota and metabolomics profiling, respectively. Enrolment began in September 2017, and study completion is expected in 2022. A total number of 1943 participants were initially recruited. Ethics and dissemination Ethical approval for data collection was granted by the National Research Ethics Committee of the Iranian Ministry of Health and Medical Education and the Research Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1395.1.149). Following the description of the study procedure, we obtained written informed consent from all study participants. Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings

Assessing the risk factors and management outcomes of ectopic pregnancy: A retrospective case-control study

Background: Ectopic pregnancy (EP) is the implantation of a fertilized egg outside the uterine cavity or in an unusual location. According to the clinical case reports, hormonal contraceptive failures may be related to emergency contraceptives and EP. EP may be treated medically, surgically, or expectantly. Currently, there is no consensus regarding whether a multiple- or double-dose regimen with methotrexate (MTX) or an additional dose could be more effective than a single-dose regimen. Objective: This study aimed to assess risk factors and treatment outcomes for EP. Materials and Methods: This case-control study was conducted in Tehran, Iran from March 2020 to March 2021. The case group was comprised of all EP-diagnosed cases (n = 191). Based on the levels of β-human chorionic gonadotropin, MTX was administered to stable individuals with no surgical indications. Risk factors were assessed through 2 control groups: intrauterine pregnancy (n = 190) and nonpregnant groups (n = 180). Results: The medical treatment significantly improved with an extra dose of MTX, especially in individuals with higher β-human chorionic gonadotropin concentrations and gestational age > 7.5 wk (p = 0.002). Considering risk factors, it is assumed that hormonal contraceptive failures, including both oral and emergency contraceptives, may increase the EP likelihood (p < 0.001). Conclusion: Based on our findings, we recommended an additional dose of MTX for subjects who are further along in their pregnancy. It is also concluded that failure of contraceptive pills increases the chances of EP. Key words: Contraception, Ectopic pregnancy, Intrauterine device, Levonorgestrel

T cell cytokine responses in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis following stimulation with proteins purified from Mycobacterium tuberculosis MDR clinical isolates

AbstractObjectiveTuberculosis (TB) is a devastating disease that remains a major health threat worldwide. The appearance of Mycobacterium tuberculosis strains resistance to current antibiotics is a growing problem, both in the third world and in developed countries. Completion of genomic sequencing of M. tuberculosis provides a strong foundation for subsequent identification of proteins to aid the understanding of protein function and the discovery of new drug targets or a TB vaccine. This study employed a proteomics approach to identify proteins from antibiotic resistant M. tuberculosis isolates and compare them to drug-sensitive isolates to determine the role of T cells in multidrug-resistant (MDR)-TB patients against M. tuberculosis-purified proteins (Rv0147) as compared with healthy subjects.MethodsProteins were extracted by Triton X-114 detergent-phase separation and precipitated by adding saturated ammonium sulfate to the supernatant. Following isoelectric focusing, proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Mass spectrometry was performed, and protein sequences were determined. Peripheral bloom mononuclear cells (PBMCs) were cultured, and autologous T cells were isolated from PBMCs by negative selection. Cells were subsequently cultured at 37°C in 5% CO2, followed by stimulation with 10μg/mL of the protein candidate (Rv0147) for 72h. Culture supernatants were assayed for interleukin (IL)-10 and interferon (IFN)-γ by enzyme-linked immunosorbent assay.ResultsThe identified proteins included Rv3057c, Rv0009, Rv3161c, Rv3614c, Rv0685, Rv2986c, Rv0443, Rv2114, Rv3311, Rv0831, Rv3804, and Rv3614c, and our results showed that the majority of upregulated or overexpressed proteins belonged to pathways associated with cellular metabolism, cell wall integrity, respiration, or cell membrane construction. Additionally, Rv1876 from MDR-TB isolates was predicted to be involved in the expression of bacterioferritin exclusively in MDR-TB-related resistance to first-line TB drugs. Furthermore, Rv2031c (HspX) was induced under oxygen-deficient conditions, and hypothetical protein (Rv2744c) and two membrane- and cell-wall-fraction proteins (Rv0379 and Rv1886c) were also identified. Analysis revealed increased percentages of INF-γ and decreased IL-10 levels in MDR-TB patients as compared with those observed in normal subjects.ConclusionFour identified membrane or membrane-associated proteins, including bacterioferritin, GroEs, HspX, and Ef-Tu, may be potential targets for the development of novel prophylactic diagnostics and therapeutic strategies against TB. Our results suggested that T cells stimulated by the protein candidate Rv0147 may be shifted to T helper 1 status in MDR-TB patients

Developing an accurate empirical correlation for predicting anti-cancer drugs’ dissolution in supercritical carbon dioxide

This study introduces a universal correlation based on the modified version of the Arrhenius equation to estimate the solubility of anti-cancer drugs in supercritical carbon dioxide (CO2). A combination of an Arrhenius-shape term and a departure function was proposed to estimate the solubility of anti-cancer drugs in supercritical CO2. This modified Arrhenius correlation predicts the solubility of anti-cancer drugs in supercritical CO2 from pressure, temperature, and carbon dioxide density. The pre-exponential of the Arrhenius linearly relates to the temperature and carbon dioxide density, and its exponential term is an inverse function of pressure. Moreover, the departure function linearly correlates with the natural logarithm of the ratio of carbon dioxide density to the temperature. The reliability of the proposed correlation is validated using all literature data for solubility of anti-cancer drugs in supercritical CO2. Furthermore, the predictive performance of the modified Arrhenius correlation is compared with ten available empirical correlations in the literature. Our developed correlation presents the absolute average relative deviation (AARD) of 9.54% for predicting 316 experimental measurements. On the other hand, the most accurate correlation in the literature presents the AARD = 14.90% over the same database. Indeed, 56.2% accuracy improvement in the solubility prediction of the anti-cancer drugs in supercritical CO2 is the primary outcome of the current study

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box–Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells

Wide Spectrum of Thyroid Function Tests in COVID-19: From Nonthyroidal Illness to Isolated Hyperthyroxinemia

Background: Changes in thyroid function test (TFT) in COVID-19 patients have been reported in several studies. However, some features such as thyrotoxicosis are inconsistent in these studies. In addition, some drugs such as heparin interfere with the free T4 assay. Objectives: This study was designed to examine TFT abnormalities in COVID-19, utilizing direct and indirect methods of free T4 assay. Methods: This prospective cross-sectional study was conducted on 131 hospitalized COVID-19 patients. Serum levels of total T3, TSH, T3RU, and total T4 were measured. The free T4 assay was performed using direct (free T4) and indirect (free thyroxin index or FT4I) methods. The patients were categorized into different TFT groups. The clinical characteristics, laboratory findings, and outcomes were compared between the groups. Results: The frequencies of Nonthyroidal Illness (NTI), subclinical/overt hypothyroidism and subclinical/overt thyrotoxicosis were 51.7, 6.9, and 6.9%, respectively. Besides, 6 and 8.1% of the patients had isolated high free T4 and isolated high FT4I without any other TFT abnormality, respectively. The lymphocyte percent was lower in the subclinical/overt group than in other TFT groups (P = 0.002). Atrial Fibrillation (AF) was found in 37.5% of subclinical/overt thyrotoxicosis patients versus 1.7% in the NTI and nil in the other three groups (P < 0.001). Conclusions: In addition to the reported TFT abnormalities in COVID-19 in previous studies, some new features like isolated hyperthyroxinemia were found in our study. We found a strong association between subclinical/overt thyrotoxicosis and AF. Regarding the high prevalence of AF in hospitalized COVID-19 patients, the thyroid function test is rational in COVID-19 patients with this arrhythmia

Surface guided 3DCRT in deep-inspiration breath-hold for left sided breast cancer radiotherapy: implementation and first clinical experience in Iran

Background: The aim of the study is to evaluate the overall accuracy of the surface-guided radiotherapy (SGRT) workflow through a comprehensive commissioning and quality assurance procedures and assess the potential benefits of deep-inspiration breath-hold (DIBH) radiotherapy as a cardiac and lung dose reduction approach for left-sided breast cancer irradiation. Materials and methods: Accuracy and reproducibility of the optical surface scanner used for DIBH treatment were evaluated using different phantoms. Patient positioning accuracy and reproducibility of DIBH treatment were evaluated. Twenty patients were studied for treatment plan quality in target dose coverage and healthy organ sparing for the two different treatment techniques. Results: Reproducibility tests for the surface scanner showed good stability within 1 mm in all directions. The maximum position variation between applied shifts on the couch and the scanner measured offsets is 1 mm in all directions. The clinical study of 200 fractions showed good agreement between the surface scanner and portal imaging with the isocenter position deviation of less than 3 mm in each lateral, longitudinal, and vertical direction. The standard deviation of the DIBH level showed a value of &lt; 2 mm during all evaluated DIBHs. Compared to the free breathing (FB) technique, DIBH showed significant reduction of 48% for heart mean dose, 43% for heart V25, and 20% for ipsilateral lung V20. Conclusion: Surface-guided radiotherapy can be regarded as an accurate tool for patient positioning and monitoring in breast radiotherapy. DIBH treatment are considered to be effective techniques in heart and ipsilateral lung dose reductions for left breast radiotherapy

Toxic epidermal necrosis following Sinopharm COVID‐19 vaccine (BBIBP‐CorV): A case report and literature review

Abstract This study reports a patient developing TEN after the first dose of (BBIBP‐CorV). He developed numerous purpuric and dusky patches with flaccid bullae and areas of epidermal detachment covered more than 30% of the body area within 6 days. After treatment with dexamethasone and cyclosporin, he recovered within 14 days

Species diversity of phytoseiid mites on different ecosystems in Sari district

Introduction Mites of the Phytoseiidae family have been extensively studied as biological control agents of different mites and insect pests. Some species also feed on nematodes, fungal spores, pollen and exudates from plants and insects. About 2,300 phytoseiid species belonging to 90 genera have been described in this family (Chant and McMurtry 2007). Considerable efforts have been made in recent years to the collection and identification of the predaceous phytoseiid mites in Iran (Rahmani et al. 2010). Despite some studies on phytoseiid mites in Iran, our knowledge remains limited about their fauna and diversity in Mazandaran province. The data of these studies showed that until recently, only 75 species were reported from Iran. The objective of this study was to evaluate the species diversity of Phytoseiidae and access to effective predatory mites for biological control of injurious mite pests in Sari, the center of Mazandaran province (Southern coast of the Caspian Sea, 35 ° 47'-36 ° 35' N, 50 ° 34'-54 ° 10' E) Materials and methods Samples were taken from 80 plant species belonging to 46 plant families including forest trees, orchards and farm crops representing three types of ecosystems from September 2011 to October 2012. Harvested samples of each plant were separately collected in plastic bags and labeled with region and date of collection. The bags were transported to the laboratory on the same day and stored in a refrigerator at about 4°C for up to a week, until the materials washed for mite extraction. Samples were composed of leaves, stems and shoots of different ages and the number of leaves per sample varied between plant species. In order to assimilate the samples, a volume nearly equal mass of each sample were put in a two-liter water container. The mites were floated on water by adding 1.5 liters of tap water and a few droplets of detergent. The plant leaves and shoots were shaken for several times until the mites fall from the plants into water. Plant materials then removed from the solution and discarded. Mites in the solution were separated by pouring the solution through sieves of 20, 50, 200 and 400 meshes. Mites transferred into a labeled glass jar for further processing and identification in the laboratory. The mites were cleared in Nesbitt's fluid and mounted in Hoyer’s medium on microscope slides. The slides were dried at 45 °C for 1-2 weeks. Then the edge of the coverslip was sealed with colorless nail polish to prevent absorption of the air moisture. All specimens collected were nominally identified to species level by using a Nikon phase contrast microscope (E600) and related identification keys. The scientific names of the plants were adapted from a dictionary of Iranian plant names (Mozaffarian 1998). The ecological indices including Margalef's richness, Simpson, Shannon-Wiener and Pielou's evenness were calculated for species diversity, dominance, richness and evenness of the mites in different ecosystems. Some mite specimens were sent to Dr. E.A. Ueckermann of the ARC-Plant Protection Research Institute, Pretoria, South Africa for identification or species confirmation. Results and discussion A total number of 946 mites of 19 species belonging to 8 genera of three phytoseiid subfamilies namely Amblyseiinae, Typhlodrominae and Phytoseiinae were identified (Table 1). Most individual mites collected in this study, 698 mites in total (73%), belonged to 12 species of the Amblyseiinae which 68% of them (475 in total) were Transeius caspiansis and 13% (90 mites in total) were Euseius amissibilis. Phytoseius plumifer, the single species of the Phytoseiinae and the species of Typhlodrominae amounted to 16% (152 in total) and 10% (96 in totals) of the collected mites, respectively. In this study Amblyseiinae also had the highest proportion of species (63%), while Typhlodrominae and Phytoseiinae had 31% and 5% of the species, respectively. Most phytoseiids collected in this study were mentioned above species that formed 76% (a total of 717) of the whole collected mites. These species were the most frequently found predators on varieties of plants. They were found on plants associated with tetranychid, tenuipalpid and eriophyid mites and small insect pests such as thrips and whiteflies. They were very common and were examined from 80 plant species, they observed on 59, 22 and 26 plants, respectively. It was interesting to observe these predators on some plants that there were not phytophagous mites. Therefore these species are generalist predators and are known to feed on pollen and exudates of plants and insects. Overall, mean mite's biodiversity indices of Margalef's richness, Simpson, Shannon-Wiener and Pielou's evenness were 1.656, 0.69, 1.546 and 0.525, respectively. Actually, when a community has many about equally abundant species, it is said to have high species diversity. But when a few species are present or like this study only a few species are abundant, then species diversity is low. The low Shannon-Wiener and Pielou's evenness indices also showed relatively low biodiversity in the area. Conclusion Despite that 19 phytoseiids species were found in Sari, the present study revealed a low diversity of phytoseiid mites in this region. Most phytoseiids collected in this area belonged to Transeius caspiansis, Euseius amissibilis and Phytoseius plumifer (a total of 717) species. However, it was expected that many additional species could be found by similar studies in the same area, especially when other plant species were sampled. The diversity of plants in the forest, orchards and farm crops were far greater than the number of plant species sampled in this study. Acknowledgments This paper is a part of MSc thesis of the senior author which was financially supported by Sari University of Agricultural Sciences and Natural Resources, Sari, Iran. Also thanks are extended to Dr. E. A. Ueckermann (Plant Protection Institute, Pretoria, South Africa who helped with the confirmation and identification of mite specimens. We also thank our colleague Dr. H. Zali for identification of some plant species. Keywords: Biodiversity indices, Biological control, Mazandaran province, Phytoseiidae References Chant, D.A., McMurtry, J.A. 2007. Illustrated keys and diagnoses for the genera and subgenera of the Phytoseiidae of the world (Acari: Mesostigmata). Indira Publishing House, Pub Michigan p. 220. Mozaffarian, V. 1998. A dictionary of Iranian plant names, Latin, English, Persian. Farhng Moaaser publication, Tehran, Iran 671 pp. Rahmani, H., Kamali, K. and Faraji, F. 2010. Predatory mite fauna of phytoseiid of northwest Iran (Acari: Mesostigmata). Turkish Journal Zoology 34: 497-508