Evaluation of Current HIV Contributions toward Progress in HIV management

Editoria

Optimization of Gamma-Aminobutyric Acid Production in Probiotics Extracted from Local Dairy Products in West Region of Iran using MRS broth and Whey Protein Media

Background and objective: Gamma-aminobutyric acid is a non-protein amino acid produced by lactic acid bacteria in fermented foods and includes unique functions in the human biological system. The aim of this study was optimization of culture media for gamma-aminobutyric acid production in probiotics extracted from local dairy products in west of Iran using two culture media of MRS broth and whey protein.Material and methods: The potential of gamma-aminobutyric acid production was assessed in Lactobacillus paracasei, Lactobacillus plantarum and Pediococos acidilactici, respectively extracted from doogh, yogurt and cheese using MRS broth and whey protein media and high performance liquid chromatography. To increase gamma-aminobutyric acid production, these media were optimized as pH (4-6), temperature (30-50°C), time (12-72 h) and glutamic acid concentration (25-250 mM).Results and conclusion: Results have shown that Lactobacillus plantarum extracted from doogh includes the highest potential of gamma-aminobutyric acid production (115.24 mg kg-1) under the following conditions of a culture temperature of 37°C, incubation time 60 h at pH 5 in MRS broth containing 50 mM of glutamic acid. After optimization of Lactobacillus plantarum media, gamma-aminobutyric acid production increased to 170.492 mg kg-1. The optimum conditions included a glutamic acid concentration of 250 mM, culture temperature at 37.27°C, pH=5.19 and an incubation time of 72 h. Based on the results, use of local isolated dairy products in west region of Iran and optimization of growth conditions increased the ability of gamma-aminobutyric acid production.Conflict of interest: The authors declare no conflict of interest

A tailored mHealth intervention for improving treatment adherence for people living with HIV in Iran (HamRaah):Protocol for a feasibility study and randomised pilot trial with a nested realist evaluation

Introduction Middle East and North Africa (MENA) has a rising rate of new HIV infections and AIDS-related mortality. Consistent adherence to antiretroviral therapy (ART) leads to viral suppression, preventing HIV transmission and treatment failure. mHealth interventions can improve ART adherence by providing tailored support and directing patients to existing healthcare services. HamRaah (Persian for ‘together-in-path’) is the first mHealth-based intervention in a MENA country and is designed to improve adherence through two-way mobile messaging for people recently diagnosed with HIV in Tehran, Iran. The objectives of this pilot randomised controlled trial (RCT) are to examine the feasibility, acceptability and preliminary effectiveness of HamRaah, and to develop an explanatory theory for any observed effects through a nested realist evaluation.Methods A feasibility study and two-arm RCT of HamRaah, with an embedded realist evaluation will be conducted. Participants will be randomised 1:1 to HamRaah or routine care for a 6-month intervention. The initial effectiveness of HamRaah will be assessed through the primary outcome of self-reported ART adherence and several secondary outcomes: retention in care, CD4 count and viral suppression. A theory-driven realist evaluation framework will be used to develop an explanatory theory regarding what works, for whom, how and in what context.Ethics and dissemination The study received ethical clearance from Tehran University of Medical Sciences Ethics Committee and Oxford Tropical Research Ethics Committee People living with HIV in Tehran and key country stakeholders in HIV policy and programming have been involved in the development of HamRaah and this pilot trial. Participants will provide informed consent prior to study enrolment. The results will be disseminated to all stakeholders and presented in peer-reviewed journal publications and conferences.Trial registration number IRCT20100601004076N23; Pre-results

Optimization and evaluation of textural properties of ultra-filtrated low-fat cheese containing galactomannan and Novagel gum

Glavni cilj ovog istraživanja bio je optimizirati teksturu i utvrditi mogućnost proizvodnje niskomasnog sira (7-9 % (w/w)) od ultrafiltriranog mlijeka uz dodatak različitih koncentracija galaktomanana i Novagela (0,1-0,5 % w/w), te ih usporediti sa sirevima od punomasnog mlijeka. Prema dobivenim rezultatima, smanjenje udjela masti rezultira povećanjem tvrdoće, kohezivnosti, gumenosti i žvakljivosti testiranih uzoraka. S druge strane, dodatak galaktomanana i Novagela, te povećanje njihove koncentracije uzrokuje smanjenje tvrdoće, kohezivnosti, gumenosti i žvakljivosti sireva. Rezultati su također pokazali kako se prethodno spomenuti parametri teksture u uzorku s 9 % (w/w) masti, 0,5 % (w/w) galaktomanana i 0,3 % (w/w) Novagela nisu značajno razlikovali od istih kod kontrolnog uzorka sira, te je stoga navedeni uzorak niskomasnog sira odabran kao optimalan. Višestruko optimiranje parametara teksture niskomasnih sireva pomoću metode odzivnih površina (RSM) pokazalo je kako uzorak s 9 % (w/w) masti, 0,1 % (w/w) Novagela i 0,46 % (w/w) galaktomanana pokazuje 84 %-tno poklapanje s poželjnim svojstvima punomasnih sireva.The general aim of this research was to optimise textural properties and to evaluate the possibility of producing ultra-filtrated low-fat cheese (7-9 % (w/w)), containing various concentrations of galactomannan and Novagel (0.1-0.5 % w/w), and assessing textural properties of produced low-fat cheeses and comparing them with full fat ones. According to the results, reducing fat implies increasing the hardness, cohesiveness, gumminess and chewiness of the tested samples. On the other hand, adding galactomannan gum and Novagel, and increasing their concentration, implies reducing all of the above mentioned textural properties. According to the results, increasing the amount of fat and using galactomannan and Novagel gum, implies increasing the adhesiveness and springiness of the tested treatments. The results showed that textural properties including hardness, adhesiveness, cohesiveness, gumminess and chewiness, of sample containing 9 % (w/w) fat, 0.5 % (w/w) galactomannan, and 0.3 % (w/w) Novagel were not of significantly different from the control sample and was selected as the superior sample. Multiple optimization of the low-fat cheeses textural properties via Response Surface Method (RSM) software showed that the treatment containing 9 % (w/w) fat, 0.1 % (w/w) Novagel and 0.46% (w/w) galactomannan fulfils 84 % of desirable properties of a full fat cheese

Mitigating losses: how scientific organisations can help address the impact of the COVID-19 pandemic on early-career researchers.

Scientific collaborations among nations to address common problems and to build international partnerships as part of science diplomacy is a well-established notion. The international flow of people and ideas has played an important role in the advancement of the 'Sciences' and the current pandemic scenario has drawn attention towards the genuine need for a stronger role of science diplomacy, science advice and science communication. In dealing with the COVID-19 pandemic, visible interactions across science, policy, science communication to the public and diplomacy worldwide have promptly emerged. These interactions have benefited primarily the disciplines of knowledge that are directly informing the pandemic response, while other scientific fields have been relegated. The effects of the COVID-19 pandemic on scientists of all disciplines and from all world regions are discussed here, with a focus on early-career researchers (ECRs), as a vulnerable population in the research system. Young academies and ECR-driven organisations could suggest ECR-powered solutions and actions that could have the potential to mitigate these effects on ECRs working on disciplines not related to the pandemic response. In relation with governments and other scientific organisations, they can have an impact on strengthening and creating fairer scientific systems for ECRs at the national, regional, and global level

Subcutaneous Injection of Allogeneic Adipose-Derived Mesenchymal Stromal Cells in Psoriasis Plaques: Clinical Trial Phase I

Objective: Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previouspre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, themechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probableefficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated.Materials and Methods: In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and twofemales (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histologicalindexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokineswere assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection)and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits.Results: No major adverse effects such as burning, pain, itching, or any systemic side effects were observed followingADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expressionlevels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expressionlevel of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCsadministration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, andscaling of the plaques, as well as the PASI score, were decreased in majority of patients.Conclusion: Our study suggested that ADSC injection could be considered as a safe and effective therapeuticapproach for psoriatic plaques (registration number: IRCT20080728001031N24)

First Report of Drug Resistance against HIV-1 Integrase Inhibitors in Iran

Background: Four Integrase Strand Transfer Inhibitors (INSTIs) have been approved for HIV-1 by the Food and Drug Administration (FDA). Recently, resistance against these INSTIs drugs and cross-resistance among them have been reported. The aim of the current study was to evaluate INSTIs drug resistant patterns in patients having virology failure to INSTIs and mutation analysis in the Nef gene. Methods: Samples were collected from individuals who had treatment failure to INSTIs. DNA and RNA were extracted by QIAamp RNA and DNA extraction kit. The PCR reaction was performed by using Qiagen one step master mix and in-house developed primers. PCR products were sequenced by Sanger method and after performing the quality control in Recall web (http://pssm.cfenet.ubc.ca/home/process_data), drug resistant mutation was analyzed by Stanford database and phylogenetic analysis was performed by MEGA5 software. Results: The phylogenetic analysis was done by 42 reference subtypes and result revealed that our sequences are in subtype CRF-35AD. The integrase major and minor mutations, T66AY143R, Y143R and T97A, showed high to intermediate resistance level to Raltegravir and Elvitegravir, respectively. The analysis of RT-RNA and proviruses revealed that pattern of drug resistance was similar in these two patients in RNA and proviruses, respectively. Moreover, analysis of the Nef sequence by codon software revealed that there were no deletion and mutation in Nef gene. Conclusion: It is the first report regarding integrase inhibitor drug resistance in Iran. Considering the wide use of antiretroviral drugs, it is necessary to determine subtype-dependent resistance in Iranian society. It is also recommended that integrase inhibitor resistance should be evaluated in naive patients, and it needs more considerations in relation to the resistance to out locate integrase

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old