Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

Diversification in the mountains: Evolutionary history and molecular phylogeny of Anatolian rock lizards.

Mountains play a key role in forming biodiversity by acting both as barriers to gene flow among populations and as corridors for the migration of populations adapted to the conditions prevailing at high elevations. The Anatolian and the Zagros Mountains are located in the Alpine-Himalayan belt. The formation of these mountains has influenced the distribution and isolation of the animal population since the late Cenozoic. Apathya is a genus of lacertid lizards distributed along these mountains with two species, i.e., Apathya cappadocica and Apathya yassujica. The taxonomy status of lineages within the genus is complicated. In this study, we tried to collect extensive samples from throughout the distribution range, especially within the Zagros Mountains. Also, we used five genetic markers, two mitochondrial (COI and Cyt b) and three nuclear (C-mos, NKTR, and MCIR), to resolve the phylogenetic relationships within the genus and explain several possible scenarios that shaped multiple genetic structures. The combination of results in the current study indicated eight well-support monophyletic lineages that separated to two main groups; group 1 including A. c. cappadocica, A. c. muhtari and A. c. wolteri, group 2 contains four regional clades Turkey, Urmia, Baneh and Ilam, and finally a single clade belonging to the species A. yassujica. In contrast to previous studies, Apathya cappadocica urmiana was divided into four clades and three clades were recognized within Iranian boundaries. The clades have dispersed from Anatolia to adjacent regions in the south of Anatolia and the western Zagros Mountains. According to the evidence generated in this study this clade is paraphyletic. Based on our assumption, orogeny activities and also climate fluctuations in Middle Miocene and Pleistocene have influenced to formation of lineages. In this study we revisit the taxonomy of the genus and demonstrate that the species diversity was substantially underestimated. Our findings suggest that each of the eight clades corresponding to subspecies and distinct geographic regions deserve to be promoted to species level.

Bridging gaps across levels of care in rehabilitation of patients with rheumatic and musculoskeletal diseases: Results from a stepped-wedge cluster randomized controlled trial.

OBJECTIVE: To compare the effectiveness of a structured goal-setting and tailored follow-up rehabilitation intervention with existing rehabilitation in patients with rheumatic and musculoskeletal diseases. DESIGN: A pragmatic stepped-wedge cluster randomized trial. SETTING: Eight rehabilitation centers in secondary healthcare, Norway. PARTICIPANTS: A total of 374 adults with rheumatic and musculoskeletal diseases were included in either the experimental (168) or the control group (206). INTERVENTIONS: A new rehabilitation intervention which comprised structured goal setting, action planning, motivational interviewing, digital self-monitoring of goal progress, and individual follow-up support after discharge according to patients' needs and available resources in primary healthcare (the BRIDGE-intervention), was compared to usual care. MAIN MEASURES: Patient-reported outcomes were collected electronically on admission and discharge from rehabilitation, and after 2, 7, and 12 months. The primary outcome was patients' goal attainment measured by the Patient Specific Functional Scale (0-10, 10 best) at 7 months. Secondary outcome measures included physical function (30-s Sit-To-Stand test), health-related quality of life (EQ-5D-5L-index), and self-assessed health (EQ-VAS). The main statistical analyses were performed on an intention-to-treat basis using linear mixed models. RESULTS: No significant treatment effects of the BRIDGE-intervention were found for either primary (Patient Specific Functional Scale mean difference 0.1 [95% CI: -0.5, 0.8], p = 0.70), or secondary outcomes 7 months after rehabilitation. CONCLUSION: The BRIDGE-intervention was not shown to be more effective than existing rehabilitation for patients with rheumatic and musculoskeletal diseases. There is still a need for more knowledge about factors that can improve the quality, continuity, and long-term health effects of rehabilitation for this patient group.

Intestinal Microbiota: Novel Personalized Cancer Immunotherapy in Colorectal Cancer.

The human colon harbors a diverse array of microorganisms that play fundamental roles in colorectal cancer (CRC). Increasing evidence indicates that dysbiosis of the intestinal microbiome has been associated with the development of CRC. Interaction between host genetics, intestinal microbiota, and lifestyle is well-indicated in the influence, prevention, and treatment of CRC. Various microbiome compositions have reported anticancer and/or anti-inflammatory properties. The presence of our microbiota is integral to our development, but a change in its composition can often lead to adverse effects, increasing the propensity for serious diseases like cancers. Recently, molecular detection and metabolomic techniques have increased our knowledge of the role of microbiota in promoting tumorigenesis. Dietary interventions may be appropriate to regulate the growth of beneficial microbiota in the gut. Metagenomic approaches along with immunology and metabolomics will obvious a new path for the treatment of CRC. In this study, we summarized recent advances in understanding the mechanisms involved in microbiota-related colorectal carcinoma, based on evidence from immunotherapy studies.

Nucleic Acids as Novel Therapeutic Modalities to Address Multiple Sclerosis Onset and Progression.

The issue of treating Multiple Sclerosis (MS) begins with disease-modifying treatments (DMTs) which may cause lymphopenia, dyspnea, and many other adverse effects. Consequently, further identification and evaluation of alternative treatments are crucial to monitoring their long-term outcomes and hopefully, moving toward personalized approaches that can be translated into clinical treatments. In this article, we focused on the novel therapeutic modalities that alter the interaction between the cellular constituents contributing to MS onset and progression. Furthermore, the studies that have been performed to evaluate and optimize drugs' efficacy, and particularly, to show their limitations and strengths are also presented. The preclinical trials of novel approaches for multiple sclerosis treatment provide promising prospects to cure the disease with pinpoint precision. Considering the fact that not a single treatment could be effective enough to cover all aspects of MS treatment, additional researches and therapies need to be developed in the future. Since the pathophysiology of MS resembles a jigsaw puzzle, researchers need to put a host of pieces together to create a promising window towards MS treatment. Thus, a combination therapy encompassing all these modules is highly likely to succeed in dealing with the disease. The use of different therapeutic approaches to re-induce self-tolerance in autoreactive cells contributing to MS pathogenesis is presented. A Combination therapy using these tools may help to deal with the clinical disabilities and symptoms of the disease in the future.

Anti-Caspr-conjugated gold nanoparticles emergence as a novel approach in the treatment of EAE animal model.

Multiple sclerosis (MS) is a chronic autoimmune disorder of central nervous system which is increasing worldwide. Although immunosuppressive agents are used for the treatment of MS disease, nevertheless the lack of non-toxic and efficient therapeutic method is perceptible. Hence, this study aims to evaluate the effect of Contactin-associated protein (Caspr) antibody-, poly ethylene glycol (PEG)- and exosome combined gold nanoparticles (GNPs) in comparison to Glatiramer acetate as a selective treatment of MS disease in the experimental autoimmune encephalomyelitis (EAE) mouse model. EAE was induced in female C57BL/6 mice and 25-day treatment with anti-Caspr-, PEG- and exosome combined GNPs was evaluated. Histopathological examination of spinal cord, regulatory T cells as well as inflammatory pathway including IFN-É£ and IL-17 and mir-326 were investigated. The results showed the severity of MS symptoms was significantly decreased in all treated groups. Histological examination of the spinal cord indicated the reduced demyelination and immune cell infiltration. Besides, regulatory T cells were significantly increased following all treatments. Remarkably, the cytokine levels of IFN-É£ and IL-17 as well as mir-326 is altered in treated groups. Taken together, the obtained findings demonstrate that the administration of anti-Caspr-, PEG- and exosome combined GNPs can be considered a potential treatment in MS disease.

Associations between quality of health care and clinical outcomes in patients with rheumatic and musculoskeletal diseases: a rehabilitation cohort study.

BACKGROUND: The quality of provided health care may be an important source of variation in rehabilitation outcomes, increasing the interest in associations between quality indicators (QIs) and improved patient outcomes. Therefore, we examined the associations between the quality of rehabilitation processes and subsequent clinical outcomes among patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: In this multicentre prospective cohort study, adults with RMDs undergoing multidisciplinary rehabilitation at eight participating centres reported the quality of rehabilitation after 2 months and outcomes after 2, 7, and 12 months. We measured perceived quality of rehabilitation by 11 process indicators that cover the domains of initial assessments, patient participation and individual goal-setting, and individual follow-up and coordination across levels of health care. The patients responded "yes" or "no" to each indicator. Scores were calculated as pass rates (PRs) from 0 to 100% (best score). Clinical outcomes were goal attainment (Patient-Specific Functional Scale), physical function (30 s sit-to-stand test), and health-related quality of life (EuroQoL 5D-5L). Associations between patient-reported quality of care and each outcome measure at 7 months was analysed by linear mixed models. RESULTS: A total of 293 patients were enrolled in this study (mean age 52 years, 76% female). Primary diagnoses were inflammatory rheumatic disease (64%), fibromyalgia syndrome (18%), unspecific neck, shoulder, or low back pain (8%), connective tissue disease (6%), and osteoarthritis (4%). The overall median PR for the process indicators was 73% (range 11-100%). The PR was lowest (median 40%) for individual follow-up and coordination across levels of care. The mixed model analyses showed that higher PRs for the process indicators were not associated with improved goal attainment or improved physical function or improved health-related quality of life. CONCLUSIONS: The quality of rehabilitation processes was not associated with important clinical outcomes. An implication of this is that measuring only the outcome dimension of quality may result in incomplete evaluation and monitoring of the quality of care, and we suggest using information from both the structure, process, and outcome dimensions to draw inferences about the quality, and plan future quality initiatives in the field of complex rehabilitation. TRIAL REGISTRATION: The study is part of the larger BRIDGE trial (ClinicalTrials.gov NCT03102814 ).

Umbilical cord mesenchymal stem cells as well as their released exosomes suppress proliferation of activated PBMCs in multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) degenerative disorder which is caused by a targeted autoimmune-mediated attack on myelin proteins. Previously, mesenchymal stem cells were considered as a novel and successful treatment of MS. One of the underlying mechanisms behind their immunomodulatory function is the release of extracellular vesicles, particularly exosomes. In this study, we aimed to evaluate the suppressive efficacy of MSCs and their exosomes on the proliferation of peripheral mononuclear blood cells (PBMC) in relapsing-remitting MS (RRMS) patients and healthy subjects. To do, mesenchymal stem cells were derived from human umbilical cord tissues and used for exosome isolation through ultracentrifugation. Suppressive function of MSCs and MSC-derived exosomes was examined in a coculture with CFSE-labelled PBMCs in vitro. PBMC proliferation of the patients and healthy individuals was measured using flow cytometry. We first demonstrated that proliferation of PBMCs decreased in the presence of MSCs and suppression was more efficient by MSC-derived exosomes, with a minimum alloreaction rate. However, suppression capacity of MSCs and their exosomes significantly decreased during extensive sub-culturing. The present study showed that MSC-derived exosomes as an effective cell-free therapy could prevent proliferation of PBMCs. However, further evaluations are need to move towards a functional approach that can be translated to the clinic.

A quality indicator set for rehabilitation services for people with rheumatic and musculoskeletal diseases demonstrates adequate responsiveness in a pre-post evaluation.

BACKGROUND: Quality of care is gaining increasing attention in research, clinical practice, and health care planning. Methods for quality assessment and monitoring, such as quality indicators (QIs), are needed to ensure health services in line with norms and recommendations. The aim of this study was to assess the responsiveness of a newly developed QI set for rehabiliation for people with rheumatic and musculoskeletal diseases (RMDs). METHODS: We used two yes/no questionnaires to measure quality from both the provider and patient perspectives, scored in a range of 0-100% (best score, 100%). We collected QI data from a multicenter stepped-wedge cluster-randomized controlled trial (the BRIDGE trial) that compared traditional rehabilitation with a new BRIDGE program designed to improve quality and continuity in rehabilitation. Assessment of the responsiveness was performed as a pre-post evaluation: Providers at rehabilitation centers in Norway completed the center-reported QIs (n = 19 structure indicators) before (T1) and 6-8 weeks after (T2) adding the BRIDGE intervention. The patient-reported QIs comprised 14 process and outcomes indicators, measuring quality in health services from the patient perspective. Pre-intervention patient-reported data were collected from patients participating in the traditional program (T1), and post-intervention data were collected from patients participating in the BRIDGE program (T2). The patient groups were comparable. We used a construct approach, with a priori hypotheses regarding the expected direction and magnitude of PR changes between T1 and T2. For acceptable responsivess, at least 75% of the hypotheses needed to be confirmed. RESULTS: All eight participating centers and 82% of the patients (293/357) completed the QI questionnaires. Responsiveness was acceptable, with 44 of 53 hypotheses (83%) confirmed for single indicators and 3 of 4 hypotheses (75%) confirmed for the sum scores. CONCLUSION: We found this QI set for rehabilitation to be responsive when applied in rehabilitation services for adults with various RMD conditions. We recommend this QI set as a timely method for establishing quality-of-rehabilitation benchmarks, promoting important progress toward high-quality rehabilitation, and tracking trends over time. TRIAL REGISTRATION: The study is part of the larger BRIDGE trial, registered at ClinicalTrials.gov (Identifier: NCT03102814).

Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies.

BACKGROUND: During the last decade, several studies have evaluated the potential association between vitamin D receptor (VDR) gene polymorphism and susceptibility to asthma. In spite of valuable findings, the results are still contradictory. Therefore, a comprehensive meta-analysis not only solves discrepancies but provides a clue for future projects. OBJECTIVE: This meta-analysis was performed to identify whether VDR gene polymorphisms (FokI (rs2228570) or TaqI (rs731236) or BsmI (rs1544410) or ApaI (rs7975232)) play a role in the risk of asthma. METHODS: Electronic search of Web of Science, Scopus, and PubMed databases were systematically conducted from their inception until June 2019, to identify all published studies. Eligibility of the studies was confirmed by precise inclusion and exclusion criteria, and the resultant studies were analyzed. RESULTS: A total of 17 studies concerning VDR gene polymorphisms and asthma risk were included in this meta-analysis. The results of pooled analysis indicated a statistically significant association between FokI SNP (dominant model [OR = 0.78, 95% CI, 0.62-0.98, random effect model] and allelic model [OR = 0.81, 95% CI, 0.67-0.98, random effect model]) and TaqI SNP (homozygote contract model [OR = 0.70, 95% CI, 0.54-0.89]) with asthma risk. Moreover, subgroup analysis showed that ethnicity influences asthma risk in Asian, African, and American populations. The sensitivity analyses confirmed the stability of the results. CONCLUSION: This meta-analysis suggests that VDR gene polymorphism is associated with the risk of asthma.

A comprehensive review on the treatment approaches of multiple sclerosis: currently and in the future.

BACKGROUND: Multiple sclerosis (MS) is a chronic and autoimmune disease of the central nervous system (CNS), mainly characterized by inflammatory demyelination, which manifests as relapses and diffuse damage and brain volume loss, both accounting for neurodegeneration, and therefore, physical disability. MS typically affects young adults and is commonly diagnosed in the early years by acute relapses, which then followed through partial or complete remission period. The clinical course of MS is characterized as four major classifications, including relapsing-remitting (RRMS), primary progressive (PPMS), progressive relapsing (PRMS), and secondary progressive (SPMS). PURPOSE: This review provides comprehensive overview of the current treatments and future innovative approaches in the treatment of MS. RESULTS: Currently, there is no definite cure for MS. The treatment of MS has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, a number of disease-modifying treatments (DMTs) have been designed that reduce the attack rate and delay progression and mainly target inflammation settings in these patients. Although remarkable advancements have occurred in the therapy of MS, the rate of progressive disability and early mortality is still worrisome. Recently, a monoclonal antibody (ocrelizumab) was demonstrated to be beneficial in a clinical trial of primary progressive MS. Furthermore, novel treatment strategies concentrating on the remyelination or neuroprotection are under evaluation. CONCLUSIONS: In spite of prosperous experiences in MS therapy, the future research, hopefully, will bring substantial improvements in the understanding and approaches of MS therapy.

Low fermentable oligo-di-mono-saccharides and polyols diet versus general dietary advice in patients with diarrhea-predominant irritable bowel syndrome: A randomized controlled trial.

BACKGROUND AND AIM: Recent evidence indicates that new approach of the diet with low fermentable oligo-di-mono-saccharides and polyols (FODMAPs) may have an effective role in management of the patients with irritable bowel syndrome (IBS). We compared the results of low FODMAP diet with current dietary treatment, general dietary advices (GDA), on the clinical response in patients with diarrhea subtype of IBS (IBS-D). METHODS: In this randomized, controlled, single-blind trial, we included 110 patients with IBS-D in two intervention groups. Participants were randomly assigned to the low FODMAP diet (n = 55) and GDA (n = 55) for 6 weeks after a 10-day screening period. Gastrointestinal symptoms and bowel habit status were evaluated using a symptom severity scoring system and Bristol stool form scale pre-intervention and post-intervention. Patients completed 3-day food diary before and after the intervention. RESULTS: Of 110 patients, 101 completed the dietary interventions. At the baseline, the nutrient intake, severity of symptoms, and demographic data were similar between two groups. After 6 weeks, the low FODMAP diet improves significantly overall gastrointestinal symptoms scores, stool frequency, and consistency versus GDA group (P < 0.001, P < 0.001, and P = 0.003, respectively). Compared with the baseline, both intervention groups expressed a significant reduction in overall scores of symptom severity scoring system, abdominal pain, distension, consistency, and frequency, but this reduction is greater in low FODMAP diet group. CONCLUSIONS: Both low FODMAP diet and GDA in patients with IBS-D led to adequate improvement of gastrointestinal symptoms for 6 weeks. However, the low FODMAP diet has greater benefits in IBS improvement.

Identification, Isolation, and Functional Assay of Regulatory T Cells.

Two categories of regulatory T cells (Tregs), nTreg and iTreg, play vital roles in orchestrating the integrity of a host in the course of an immune response. Tregs commonly belong to CD4+ CD25+ T cells and they are characterized by a transcription factor - forkhead box P3 (FoxP3). Within the space of the last few years, interests have been drawn to Tregs as a therapeutic tool in several settings like autoimmune disease, transplantation, and tumor disorders. As a consequence, to assess the functional properties of Tregs, namely through their ability to suppress other cells, cytokine expression, and proliferation in a variety of conditions, it is mandatory to gain better approaches to this end. This would be beneficial in designing better-than-ever therapeutic methods with regard to Tregs properties. Gaining better insights into the underlying mechanisms of immune regulation, by means of straightforward and less time-consuming techniques, will hopefully permit the therapeutic application of these cells in the control of human disorders. This review aims at going through the basic methods for Treg isolation as well the efficiency of the commonly exerted in vitro assays of Tregs-mediated immune suppression.

Effects of a traditional herbal formula containing Melissa officinalis, Pimpinella anisum, and Rosa damascena on anxiety and depression in patients with constipation-predominant irritable bowel syndrome (IBS-C): A double-blind randomized clinical trial.

INTRODUCTION: Irritable bowel syndrome (IBS) is associated with a high prevalence of anxiety and depression. This study aimed to evaluate the effects of a traditional Persian herbal formula containing Melissa officinalis, Pimpinella anisum, and Rosa damascena (MPR) on anxiety and depression in IBS patients with symptoms of constipation-predominant IBS (IBS-C). METHODS: This double-blind randomized clinical trial was conducted in Afzalipour Hospital via block randomization method. A total of 96 IBS-C patients (based on Rome IV criteria), aged 18-60 years, were included in this study. Participants received capsules containing either 500 mg of herbal formula or placebo (cornstarch) twice a day for four weeks Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. RESULTS: Forty-three patients in the intervention group and 45 patients in the control group completed this study. Except for the education level, there were no significant differences in the demographic characteristics between the two groups (P > 0.05). The mean levels of anxiety and depression, and total IBS symptom severity score showed no significant differences between the two groups at baseline (P > 0.05). After four weeks of treatment, the anxiety score considerably improvement in the treatment group (Cohen's d = -1.19, 95 % confidence intervals [CIs] -4.49 to 2.13), as did the depression score (Cohen's d = -1.93, 95 % CIs -4.32 to 2.79). CONCLUSION: MPR considerably improved anxiety and depression in patients with IBS-C compared to the placebo without serious side effects.

Delivery of a quality improvement program in team-based rehabilitation for patients with rheumatic and musculoskeletal diseases: a mixed methods study.

PURPOSE: To investigate how a quality improvement program (BRIDGE), designed to promote coordination and continuity in rehabilitation services, was delivered and perceived by providers in routine practice for patients with rheumatic and musculoskeletal diseases. METHODS: A convergent mixed methods approach was nested within a stepped-wedge, randomized controlled trial. The intervention program was developed to bridge gaps between secondary and primary healthcare, comprising the following elements: motivational interviewing; patient-specific goal setting; written rehabilitation-plans; personalized feedback on progress; and tailored follow-up. Data from health professionals who delivered the program were collected and analyzed separately, using two questionnaires and three focus groups. Results were integrated during the overall interpretation and discussion. RESULTS: The program delivery depended on the providers' skills and competence, as well as on contextual factors in their teams and institutions. Suggested possibilities for improvements included follow-up with sufficient support from next of kin and external services, and the practicing of action and coping plans, standardized outcome measures, and feedback on progress. CONCLUSIONS: Leaders and clinicians should discuss efforts to ensure confident and qualified rehabilitation delivery at the levels of individual providers, teams, and institutions, and pay equal attention to each component in the process from admission to follow-up.

Quality in rehabilitation should be characterized by a continuous and coordinated process from goal setting to follow-up.To improve the quality, sufficient involvement of next of kin and external services is needed.Clinicians may need training to build confidence in motivational interviewing, action- and coping planning, feedback on progress, and follow-up.Leaders should organize education sessions, optimize schedules, insert standardized outcome measures, and facilitate collaboration across levels of care and services.

Does follow-up really matter? A convergent mixed methods study exploring follow-up across levels of care in rehabilitation of patients with rheumatic and musculoskeletal diseases.

PURPOSE: To explore what patients with rheumatic and musculoskeletal diseases (RMDs) need and receive of follow-up care after specialized rehabilitation, and whether received follow-up is associated with health outcomes after 1 year. Further, to compare these findings with patients' experiences to improve the understanding of how follow-up takes place. METHODS: In a mixed methods study, patients received a rehabilitation programme designed to improve the continuity in rehabilitation across care levels. A total of 168 patients completed questionnaires, of which 21 were also interviewed. RESULTS: At discharge, most patients reported needs for follow-up. These needs were largely met within 1 year, mainly resulting from patients' initiatives to re-connect with previous contacts. The degree of received follow-up was not associated with goal attainment, quality of life, or physical function. Factors related to providers (competence, communication skills), context (delays, limited access to care), and patients (motivation, life situation, preferences) seemed to be decisive for the progress of the rehabilitation process over time. CONCLUSIONS: The results provide evidence that access to follow-up care is crucial to patients with RMDs. However, it also highlights several factors that may influence its impact. These results can be used to optimise design and implementation of future follow-up interventions.

Healthcare providers should take greater responsibility for creating continuity in rehabilitation across levels of care.Follow-up care should be adapted to patients' needs, goals, and preferences as regards content, timing, and mode of delivery.Follow-up should be linked to a rehabilitation plan for each patient to ensure continuity of care.More effective communication systems across service levels should be established.

Safety and immunogenicity of COReNAPCIN, a SARS-CoV-2 mRNA vaccine, as a fourth heterologous booster in healthy Iranian adults: A double-blind, randomized, placebo-controlled, phase 1 clinical trial with a six-month follow-up.

The recurrent COVID-19 infection, despite global vaccination, highlights the need for booster doses. A heterologous booster has been suggested to enhance immunity and protection against emerging variants of concern of the SARS-CoV-2 virus. In this report, we aimed to assess the safety, and immunogenicity of COReNAPCIN, as a fourth booster dose after three doses of inactivated vaccines. METHODS: The study was conducted as a double-blind, randomized, placebo-controlled phase 1 clinical trial of the mRNA-based vaccine candidate, COReNAPCIN. The vaccine was injected as a heterologous booster in healthy Iranian adults aged 18-50 who had previously received three doses of inactivated SARS-CoV-2 vaccines. In the study, 30 participants were randomly assigned to receive either COReNAPCIN in two different doses (25 µg and 50 µg) or placebo. The vaccine candidate contained mRNA encoding the complete sequence of the pre-fusion stabilized Spike protein of SARS-CoV-2, formulated within lipid nanoparticles. The primary endpoint was safety and the secondary objective was humoral immunogenicity until 6 months post-vaccination. The cellular immunogenicity was pursued as an exploratory outcome. RESULTS: COReNAPCIN was well tolerated in vaccinated individuals in both doses with no life-threatening or other serious adverse events. The most noticeable solicited adverse events were pain at the site of injection, fatigue and myalgia. Regarding the immunogenicity, despite the seroprevalence of SARS-CoV-2 antibodies due to the vaccination history for all and previous SARS-CoV-2 infection for some participants, the recipients of 25 and 50 µg COReNAPCIN, two weeks post-vaccination, showed 6·6 and 8·1 fold increase in the level of anti-RBD, and 11·5 and 21·7 fold increase in the level of anti-spike antibody, respectively. The geometric mean virus neutralizing titers reached 10.2 fold in the 25 µg group and 8.4 fold in 50 µg group of pre-boost levels. After 6 months, the measured anti-spike antibody concentration still maintains a geometric mean fold rise of 2.8 and 6.3, comparing the baseline levels in 25 and 50 µg groups, respectively. Additionally, the significant increase in the spike-specific IFN-ϒ T-cell response upon vaccination underscores the activation of cellular immunity. CONCLUSION: COReNAPCIN booster showed favorable safety, tolerability, and immunogenicity profile, supporting its further clinical development (Trial registration: IRCT20230131057293N1).

A double-blind randomized clinical trial of Dracocephalum kotschyi Boiss. in the patients with diarrhea-predominant irritable bowel syndrome.

Background and purpose: Irritable bowel syndrome (IBS) is a disease that shows its impacts on many populations worldwide. It is known as a functional disorder of the gastrointestinal tract followed by diarrhea and fecal inconsistency. Due to the lack of treatment in the allopathic medicine system for IBS, people in the western world use different herbs as alternative medicine. In the present study, we evaluated the dried extract of Dracocephalum kotschyi against IBS. Experimental approach: In a randomized, double-blinded, placebo-controlled clinical trial, 76 diarrhea-predominant IBS patients were randomly assigned to two equal groups: the control group (given the placebo capsule containing 250 mg of dibasic calcium phosphate) and the treatment groups (given the capsule containing 75 mg of the dry extract of D. kotschyi and 175 mg of dibasic calcium phosphate as filler). The study was conducted based on Rome III criteria. We studied symptoms included in Rome III criteria and divided the study into the duration of drug administration and four weeks after drug administration. These groups were compared with those of the control group. Findings/Results: Significant improvements were found in the quality of life, temperament, and IBS symptoms throughout the treatment duration. Quality of life, temperature, and IBS symptoms were slightly decreased in the treatment group 4 weeks after stopping the treatment. While concluding the study, we found D. kotschyi effective against IBS. Conclusion and implications: Whole extract of D. kotschyi modulated symptoms of IBS patients and improved their quality of life.

The threat of a non-native oligochaete species in Iran's freshwater: assessment of the diversity and origin of Eiseniella tetraedra (Savigny, 1826) and its response to climate change.

Oligochaetes are the most abundant benthic taxa in aquatic ecosystems that play an important role in food webs. The present study aims to assess the diversity and origin of Eiseniella tetraedra as a non-native species in the Lar National Park of Iran and also its response to current and future climate change. We obtained the specimen from rivers and sequenced the mitochondrial gene Cytochrome Oxidase subunit I (COI) and combined them with 117 sequences from the Jajroud and Karaj rivers in Iran and native regions from GenBank (NCBI). We also ran Species Distribution Modelings (SDMs) using an ensemble model approach that was estimated according to two shared socio-economic pathways (SSPs): 126 and 585 of the MRI-ESM2 based on CMIP6. According to the results, all the samples examined in the current study originated from Spanish rivers, and no unique haplotype was found in the Lar National Park. Moreover, the results also show high haplotype diversity that can positively affect the success of this non-native species in different freshwater. Also, the results of SDMs depict that climate change would remarkably affect the distribution of E. tetraedra and it verifies the invasion power of E. tetraedra in Iran's freshwater ecosystems over time.

Global Trend on Machine Learning in Helicobacter within One Decade: A Scientometric Study.

Purpose: This study aims to create a science map, provide structural analysis, investigate evolution, and identify new trends in Helicobacter pylori (H. pylori) research articles. Methods: All Helicobacter publications were gathered from the Web of Science (WoS) database from August 2010 to 2021. The data were required for bibliometric analysis. The bibliometric analysis was performed with Bibliometrix R Tool. Bibliometric data were analyzed using the Bibliometrix Biblioshiny R-package software. Results: A total of 17,413 articles were reviewed and analyzed, with descriptive characteristics of the H. pylori literature included. In journals, 21,102 keywords plus and 20,490 author keywords were reported. These articles were also written by 56,106 different authors, with 262 being single-author articles. Most authors' abstracts, titles, and keywords included "Helicobacter-pylori." Since 2010, the total number of H. pylori-related publications has been decreasing. Gut, PLOS ONE, and Gastroenterology are the most influential H. pylori journals, according to source impact. China, the United States, and Japan are the countries with most affiliations and subjects. In addition, Seoul National University has published the most articles about H. pylori. According to the cloud word plot, the authors' most frequently used keywords are gastric cancer (GC), H. pylori, gastritis, eradication, and inflammation. "Helicobacter pylori" and "infection" have the steepest slopes in terms of the upward trend of words used in articles from 2010 to 2021. Subjects such as GC, intestinal metaplasia, epidemiology, peptic ulcer, eradication, and clarithromycin are included in the diagram's motor theme section, according to strategic diagrams. According to the thematic evolution map, topics such as Helicobacter pylori infection, B-cell lymphoma, CagA, Helicobacter pylori, and infection were largely discussed between 2010 and 2015. From 2016 to 2021, the top topics covered included Helicobacter pylori, H. pylori infection, and infection.