Comparative Analysis of Apigenin-3 Acetate versus Apigenin and Methyl-Prednisolone in Inhibiting Proliferation and Gene Expression of Th1 Cells in Multiple Sclerosis

Objective: In spite of the advances in therapeutic modalities, morbidity, due to multiple sclerosis (MS), still remains high.Therefore, a large body of research is endeavouring to discover or develop novel therapies with improved efficacy fortreating MS patients. In the present study, we examined the immunomodulatory effects of apigenin (Api) on peripheralblood mononuclear cells (PBMCs) isolated from MS patients. We also developed an acetylated form of Api (apigenin-3-acetate) to improve In its blood-brain barrier (BBB) permeability. Additionally, we compared its anti-inflammatoryproperties to original Api and methyl-prednisolone-acetate (a standard therapy), as a potential option in treating MSpatients.Materials and Methods: The current study was an experimental-interventional research. The half maximal inhibitoryconcentration (IC50) values for apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate were determined inhealthy volunteers’ PBMCs (n=3). Gene expressions of T-box transcription factor (TBX21 or T-bet) and IFN-γ, as wellas proliferation of T cells isolated from MS patients’ PBMCs (n=5), were examined in co-cultures of apigenin-3-acetate,Api and methyl-prednisolone-acetate after 48 hours of treatment, using quantitative reverse transcription polymerasechain reaction (qRT-PCR).Results: Our findings showed that apigenin-3-acetate, apigenin, and methyl-prednisolone-acetate at concentrations of80, 80, and 2.5 M could inhibit Th1 cell proliferation after 48 hours (P=0.001, P=0.036, and P=0.047, respectively); theyalso inhibited T-bet (P=0.015, P=0.019, and P=0.022) and interferon-γ (IFN-γ) gene expressions (P=0.0001).Conclusion: Our findings suggested that Api may have anti-inflammatory properties, possibly by inhibiting proliferationof IFN-producing Th1 cells. Moreover, comparative immunomodulatory effects were found for the acetylated version ofapigenin-3-acetate versus Api and methyl-prednisolone-acetate

In Vitro Cytotoxicity Of Folate-Silica-Gold Nanorods On Mouse Acute Lymphoblastic Leukemia And Spermatogonial Cells

Objective The purpose of this study was to evaluate in vitro cytotoxicity of gold nanorods (GNRs) on the viability of spermatogonial cells (SSCs) and mouse acute lymphoblastic leukemia cells (EL4s). Materials And Methods In this experimental study, SSCs were isolated from the neonate mice, following enzymatic digestion and differential plating. GNRs were synthesized, then modified by silica and finally conjugated with folic acid to form F-Si-GNRs. Different doses of F-Si-GNRs (25, 50, 75, 100, 125 and 140 µM) were used on SSCs and EL4s. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed to examine the GNRs toxicity. Flow cytometry was used to confirm the identity of the EL4s and SSCs. Also, the identity and functionality of SSCs were determined by the expression of specific spermatogonial genes and transplantation into recipient testes. Apoptosis was determined by flow cytometry using an annexin V/propidium iodide (PI) kit. Results Flow cytometry showed that SSCs and EL4s were positive for Plzf and H-2kb, respectively. The viability percentage of SSCs and EL4s that were treated with 25, 50, 75, 100, 125 and 140 µM of F-Si-GNRs was 65.33 ± 3.51%, 60 ± 3.6%, 51.33 ± 3.51%, 49 ± 3%, 30.66 ± 2.08% and 16.33 ± 2.51% for SSCs and 57.66 ± 0.57%, 54.66 ± 1.5%, 39.66 ± 1.52%, 12.33 ± 2.51%, 10 ± 1% and 5.66 ± 1.15% for EL4s respectively. The results of the MTT assay indicated that 100 µM is the optimal dose to reach the highest and lowest level of cell death in EL4s and in SSCs, respectively. Conclusion Cell death increased with increasing concentrations of F-Si-GNRs. Following utilization of F-Si-GNRs, there was a significant difference in the extent of apoptosis between cancer cells and SSCs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Telepractice Parent Training of Enhanced Milieu Teaching With Phonological Emphasis (EMT+PE) For Persian-Speaking Toddlers With Nonsyndromic Cleft Palate: Protocol for a Randomized Controlled Trial

BackgroundChildren born with a cleft palate with or without a cleft lip (CP/L) are at increased risk for delayed language development and speech sound disorders. Enhanced Milieu Teaching with Phonological Emphasis (EMT+PE) is a recommended naturalistic intervention for toddlers with CP/L. The parents’ role in providing naturalistic interventions is critical and they need training based on learning principles to implement these interventions. Telepractice is an appropriate method for training parents and children with various speech-related disorders. ObjectiveThis study aims to determine and compare the effectiveness of telepractice and the parent-implemented EMT+PE intervention on language and speech measures in toddlers with CP/L with usual interventions and determine the effectiveness maintenance of the intervention. MethodsA randomized controlled trial (RCT) will assess the efficacy of telepractice and the parent-implemented EMT+PE intervention in enhancing speech and language measures in toddlers with CP/L. Eligible participants will be randomly assigned to one of 2 groups: the conventional intervention group and the EMT+PE intervention group. Participants’ speech and language measures will be evaluated remotely by trained raters before and after the intervention and 2 months after the intervention. Parents of participants in the intervention group will receive 3 months of training in speech and language supportive strategies from trained therapists using telehealth fidelity scales. Parents of participants in the control group will receive the conventional speech and language intervention by cleft team therapists. Study outcomes will include language variables (mean length of utterance) and speech production variables (percent correct consonants). ResultsThe protocol was approved by the Research Ethics Committee of the University of Social Welfare and Rehabilitation Sciences in February 2022. The selection process of participants, as well as training therapists and raters, commenced in January 2022, the therapy and follow-up period ended in June 2023, and pre- and postintervention assessments have been conducted. Data analysis is ongoing, and we expect to publish our results by the summer of 2024. Funding is yet to be received. ConclusionsThe results of this study may help us develop a speech and language intervention with a different delivery model for toddlers with CP/L, and the cleft team care can use these results in service delivery. Consistent with our hypothesis, speech and language measures are expected to improve. International Registered Report Identifier (IRRID)DERR1-10.2196/5442

Policy Solutions to End Gaps in Medicaid Coverage during Reentry after Incarceration in the United States: Experts Recommendations.

AIMS: We sought to gather experts perspectives on Medicaid coverage gaps during reentry to identify high-yield policy solutions to improve the health of justice-involved individuals in the United States. SUBJECT AND METHODS: We interviewed 28 experts at the intersection of Medicaid and criminal justice via telephone between November 2018 and April 2019. Interviewees included Medicaid administrators, health and justice officials, policy makers, and health policy researchers. We performed thematic analysis of semi-structured interview transcripts to identify emergent themes and distill policy recommendations. RESULTS: Three themes emerged: 1) Medicaid coverage gaps during reentry contribute to poor health outcomes and recidivism, 2) Excessive burden on justice-involved people to re-activate Medicaid leads to coverage gaps, and 3) Scalable policy solutions exist to eliminate Medicaid coverage gaps during reentry. Policy recommendations centered on ending the federal inmate exclusion, delaying Medicaid de-activation at intake, and promoting re-activation by reentry. Experts viewed coverage gaps as problematic, viewed current approaches as inefficient and burdensome to families and systems, and recommended several policy solutions. CONCLUSION: By pursuing strategies to eliminate Medicaid gaps during reentry, policymakers can improve health outcomes and efficiency of government spending on healthcare, and may reduce cycles of incarceration

Reducing Medicaid Coverage Gaps for Youth During Reentry

Although many justice-involved youth (JIY) rely on Medicaid, due to the federal "inmate exclusion" Medicaid is often suspended or terminated upon youth's intake to detention, which can lead to coverage gaps at release. We interviewed 28 experts on Medicaid and the justice system and conducted thematic analysis to identify solutions for reducing Medicaid coverage gaps during reentry. Participants viewed coverage gaps during reentry as a significant public health problem to which JIY are especially vulnerable. Recommended solutions for reducing coverage gaps for JIY included (a) leave Medicaid activated, (b) reactivate Medicaid before or during reentry, (c) enhance interagency collaboration, and (d) address societal context to ensure health care access for Medicaid-eligible JIY. Doing so may improve health outcomes and reduce cycles of youth incarceration

Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases

Background Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. Objectives This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. Design This prospective observational study was designed in a tertiary center during one year. Methods All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Results Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). Conclusion The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females

Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia

Objectives: Saffron is the stigma of Crocus sativus L., which has the potentials to play a role in the treatment of many diseases. Although many researches are now going on this precious spice, there are few data on saffron safety in human, especially in patients with chronic mental illnesses. This study aimed to evaluate the short-term safety and tolerability of both saffron and crocin (its major constituent) in adult patients with schizophrenia. Materials and Methods: The capsules of saffron aqueous extract (SAE) and crocin were used to evaluate short-term safety and tolerability in patients with schizophrenia. A double-blind, placebo-controlled study was performed on patients with schizophrenia. The patients were all male and were divided into three 22-patient groups. While receiving their normal treatment, they also received a 12 week treatment with SAE (15 mg twice daily), crocin (15 mg twice daily) or placebo. Results: A total of 61 patients completed the trial; none of them reported a serious side effect. WBC count increased significantly in patients receiving saffron aqua extract (SAE), but it was within the normal range and had no clinical significance. Other hematologic components, markers of thyroid, liver and kidney or inflammation markers had no statistically significant difference among the groups. Conclusions: This study showed that SAE and crocin in doses of 15 mg twice daily were safely tolerated in patients with schizophrenia