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Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021–April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a "washout period" for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55–62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits. [ABSTRACT FROM AUTHOR]

Background: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. Methods: Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. Results: Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. Conclusion: Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH. [ABSTRACT FROM AUTHOR]

Researchers who aim to globally analyze the gastrointestinal immune system via flow cytometry have many protocol options to choose from, with specifics generally tied to gut wall layers of interest. To get a clearer idea of the approach we should use on full-thickness colon samples from mice, we first undertook a systematic comparison of three tissue dissociation techniques: two based on enzymatic cocktails and the other one based on manual crushing. Using flow cytometry panels of general markers of lymphoid and myeloid cells, we found that the presence of cell-surface markers and relative cell population frequencies were more stable with the mechanical method. Both enzymatic approaches were associated with a marked decrease of several cell-surface markers. Using mechanical dissociation, we then developed two minimally overlapping panels, consisting of a total of 26 antibodies, for serial profiling of lymphoid and myeloid lineages from the mouse colon in greater detail. Here, we highlight how we accurately delineate these populations by manual gating, as well as the reproducibility of our panels on mouse spleen and whole blood. As a proof-of-principle of the usefulness of our general approach, we also report segment- and life stage-specific patterns of immune cell profiles in the colon. Overall, our data indicate that mechanical dissociation is more suitable and efficient than enzymatic methods for recovering immune cells from all colon layers at once. Additionally, our panels will provide researchers with a relatively simple tool for detailed immune cell profiling in the murine gastrointestinal tract, regardless of life stage or experimental conditions. [ABSTRACT FROM AUTHOR]

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH. [ABSTRACT FROM AUTHOR]

COVID-19 breakthrough infection (BTI) can occur despite vaccination. Using a multi-centre, prospective, observational Canadian cohort of people with HIV (PWH) receiving ≥2 COVID-19 vaccines, we compared the SARS-CoV-2 spike (S) and receptor-binding domain (RBD)-specific IgG levels 3 and 6 months post second dose, as well as 1 month post third dose, in PWH with and without BTI. BTI was defined as positivity based on self-report measures (data up to last study visit) or IgG data (up to 1 month post dose 3). The self-report measures were based on their symptoms and either a positive PCR or rapid antigen test. The analysis was restricted to persons without previous COVID-19 infection. Persons without BTI remained COVID-19-naïve until ≥3 months following the third dose. Of 289 participants, 92 developed BTI (31.5 infections per 100 person-years). The median days between last vaccination and BTI was 128 (IQR 67, 176), with the most cases occurring between the third and fourth dose (n = 59), corresponding to the Omicron wave. In analyses adjusted for age, sex, race, multimorbidity, hypertension, chronic kidney disease, diabetes and obesity, a lower IgG S/RBD (log10 BAU/mL) at 1 month post dose 3 was significantly associated with BTI, suggesting that a lower IgG level at this time point may predict BTI in this cohort of PWH. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. Methods: CHACS is a multi‐centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow‐up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender—gender roles, gender identity, gender relationships, and institutionalized gender—will be measured using the GENESIS‐PRAXY questionnaire. Diet will be assessed using a validated, web‐based, self‐administered food frequency questionnaire. Results: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50–61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. Conclusions: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio‐economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses. [ABSTRACT FROM AUTHOR]

Few studies have examined preventative behaviour practices with respect to COVID-19 among people living with HIV (human immunodeficiency virus). Using a cross-sectional survey from a Canadian Institutes of Health Research Canadian HIV Trials Network study (CTN 328) of people living with HIV on vaccine immunogenicity, we examined the relationships between participant characteristics and behavioural practices intended to prevent COVID-19 infection. Participants living in four Canadian urban centers were enrolled between April 2021–January 2022, at which time they responded to a questionnaire on preventative behaviour practices. Questionnaire and clinical data were combined to explore relationships between preventive behaviours and (1) known COVID-19 infection pre-enrolment, (2) multimorbidity, (3) developing symptomatic COVID-19 infection, and (4) developing symptomatic COVID-19 infection during the Omicron wave. Among 375 participants, 49 had COVID-19 infection pre-enrolment and 88 post-enrolment. The proportion of participants reporting always engaging in preventative behaviours included 87% masking, 79% physical distancing, 70% limiting social gatherings, 65% limiting contact with at-risk individuals, 33% self-isolating due to symptoms, and 26% self-quarantining after possible exposure. Participants with known COVID-19 infection pre-enrolment were more likely to self-quarantine after possible exposure although asymptomatic (65.0% vs 23.4%, p < 0.001; Chi-square test). Participants with multiple comorbidities more likely endorsed physical distancing (85.7% vs 75.5%, p = 0.044; Chi-square test), although this was not significant in logistic regression analysis adjusted for age, sex, race, number of household members, number of bedrooms/bathrooms in the household per person, influenza immunization, and working in close physical proximity to others. Overall, participants reported frequent practice of preventative behaviours. [ABSTRACT FROM AUTHOR]

Background: The differentiation and function of immunosuppressive regulatory T cells (Tregs) is dictated by the master transcription factor FoxP3. During HIV infection, there is an increase in Treg frequencies in the peripheral blood and lymphoid tissues. This accentuates immune dysfunction and disease progression. Expression of FoxP3 by thymic Tregs (tTregs) is partially controlled by TGF-β. This cytokine also contributes to Treg development in the peripheral blood and lymphoid tissues. Although TGF-β mediates lymphoid tissue fibrosis and peripheral Treg differentiation in HIV-infected individuals, its role in the induction and maintenance of Tregs within the thymus during HIV infection remains unclear. Methods: Thymocytes were isolated from fresh human thymic tissues obtained from pediatric patients undergoing cardiac surgery. Infection by both R5- and X4- tropic HIV-1 strains and TGF-β treatment of human thymocytes was performed in an in vitro co-culture model with OP9-DL1 cells expressing Notch ligand deltalike 1 without T cell receptor (TCR) activation. Results: Despite high expression of CCR5 and CXCR4 by tTregs, FoxP3 + CD3highCD8- thymocytes were much less prone to in vitro infection with R5- and X4-tropic HIV strains compared to FoxP3-CD3highCD8- thymocytes. As expected, CD3highCD4+ thymocytes, when treated with TGF-β1, upregulated CD127 and this treatment resulted in increased FoxP3 expression and Treg differentiation, but did not affect the rate of HIV infection. FoxP3 expression and Treg frequencies remained unchanged following in vitro HIV infection alone or in combination with TGF-β1. Conclusion: FoxP3 expression and tTreg differentiation is not affected by in vitro HIV infection alone or the combination of in vitro HIV infection and TGF-β treatment. [ABSTRACT FROM AUTHOR]

Currently, there is no cure for human immunodeficiency virus type 1 (HIV-1) infection. However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles, and are released from cells as a form of intercellular communication. This study investigates the impact of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308, on the EVs released from HIV-1-infected myeloid cells as well as HIV-1-infected 3D neurospheres. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1β and TNF-α mRNA. This decrease in viral RNA occurs in in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, and infected neurospheres. Furthermore, a 3D neurosphere model shows an overall decrease in proinflammatory mRNA with HU308. Finally, using a humanized mouse model of HIV-1 infection, plasma viral RNA was shown to significantly decrease with HU308 alone and was most effective in combination with cART, even when compared to the typical cART treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART. [ABSTRACT FROM AUTHOR]

Chronic HIV infection is characterized by persistent inflammation despite antiretroviral therapy (ART). Cannabinoids may help reduce systemic inflammation in people with HIV (PWH). To assess the effects of oral cannabinoids during HIV, ten PWH on ART were randomized (n = 5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (2.5:2.5–15:15 mg/day) capsules or CBD-only (200–800 mg/day) capsules for 12 weeks. Blood specimens were collected prospectively 7–21 days prior to treatment initiation and at weeks 0 to 14. Plasma cytokine levels were determined via Luminex and ELISA. Immune cell subsets were characterized by flow cytometry. HIV DNA/RNA were measured in circulating CD4 T-cells and sperm by ultra-sensitive qPCR. Results from both arms were combined for statistical analysis. Plasma levels of IFN- γ , IL-1 β , sTNFRII, and REG-3α were significantly reduced at the end of treatment (p ˂ 0.05). A significant decrease in frequencies of PD1+ memory CD4 T-cells, CD73+ regulatory CD4 T-cells, and M-DC8+ intermediate monocytes was also observed (p ˂ 0.05), along with a transient decrease in CD28–CD57+ senescent CD4 and CD8 T-cells. Ki-67+ CD4 T-cells, CCR2+ non-classical monocytes, and myeloid dendritic cells increased over time (p ˂ 0.05). There were no significant changes in other inflammatory markers or HIV DNA/RNA levels. These findings can guide future large clinical trials investigating cannabinoid anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

This study examined the feasibility of using ecological momentary assessment (EMA) to disentangle medicinal cannabis use (MCU) from recreational cannabis use (RCU) among people living HIV (PLWH). Over a 14-day period, PLWH (N = 29) who engaged in both MCU and RCU completed a smartphone-based survey before and after every cannabis use event assessing general motivation for cannabis use (MCU-only, RCU-only, or mixed MCU/RCU), cannabis use behavior, and several antecedents and outcomes of cannabis use. A total of 739 pre-cannabis surveys were completed; 590 (80%) of the prompted post-cannabis surveys were completed. Motives for cannabis use were reported as MCU-only on 24%, RCU-only on 30%, and mixed MCU/RCU on 46% of pre-cannabis surveys. Mixed effects models examined within-person differences across MCU-only, RCU-only, and mixed MCU/RCU events. Results showed that relative to RCU-only events, MCU-only events were more likely to involve symptom management and drug substitution motives, physical and sleep-related symptoms, solitary cannabis use, and use of cannabis oils and sprays; MCU-only events were less likely to involve relaxation, happiness, and wellness motives, cannabis flower use, and positive cannabis consequences. Differences between mixed MCU/RCU and RCU-only events were similar, except that mixed MCU/RCU events were additionally associated with stress reduction motives and symptoms of anxiety and depression. Findings support the feasibility of partially disentangling MCU and RCU behavior among PLWH who engage in concurrent MCU and RCU. This study highlights the need for more EMA studies isolating MCU from RCU to inform ongoing changes to cannabis policies. [ABSTRACT FROM AUTHOR]

We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation. [ABSTRACT FROM AUTHOR]

Introduction: Considering that nutrition plays a prominent role in the health of the elderly, oral health and the associated quality of life are very important for a healthy diet. The aim of this study was to investigate the association between the frequency of fruit and vegetable consumption and oral health-related quality of life (OHRQoL) among the elderly in Amirkola. Materials & Methods: This study was part of the second phase of the Amirkola elderly cohort study conducted on750 older people who underwent a special oral and dental examination in 2016-2020 using the Oral Health Questionnaire. The frequency of fruit and vegetable consumption was assessed with the Semi- Quantitative Food Frequency Questionnaire (SQFFQ), OHRQoL was assessed with the General Oral Health Assessment Index (GOHAI), and information on age, sex, history of systemic diseases, and the number of teeth was extracted from the full data set completed by specialists for each patient. Data were analyzed with SPSS 20 using the chi-square statistical test, ANOVA, and Pearson correlation coefficient. A value of p<0.05 was considered significant. Results: Non-smokers and people with a higher level of education had a better OHRQoL (P=0.022 and P=0.036, respectively). There was no significant relationship between the frequency of fruit and vegetable consumption and OHRQoL, but a significant relationship was found between the frequency of fresh herb consumption and OHRQoL (p=0.005). In men, there was a significant relationship between the number of teeth and frequency of vegetable consumption as well as between OHRQoL and frequency of fresh herb consumption in men (P=0.048, r=0.096). In women, a significant relationship was observed between the frequency of total vegetable consumption and OHRQoL (p=0.021, r=0.129). Conclusion: According to the results of the present study,it was found that the amount of fruit and vegetable consumption has no effect on improving the OHRQoL among the elderly of Amirkola city. [ABSTRACT FROM AUTHOR]

Introduction: Nifedipine (NF) is a calcium channel blocker that accelerates wound healing and subsequently relieves pain and discomfort. The aim of the present study was to investigate the local effect of this drug on the wound healing process of the palate. Materials & Methods: In this triple-blind clinical trial study, 31 patients who were referred to the Periodontology Department of Babol Dental School (14 in the experimental group and 17 in the control group) were examined. They were candidates for gingival surgery and needed a palate transplant. Mucotom was used to create identical wounds in the palate (transplant donor). After a free gingival grafting, the active ingredient of 0.3% NF was applied as a mucosal adhesive (made of chitosan) in the area of the graft (palate). Patients were examined and recorded on days 2, 4, 7, 14, and 30 after surgery for wound closure and healing criteria (Landry & Manchester scar scale) and pain (VAS). Sutures were removed on day 7 of the study. Data were analyzed with SPSS 20 and chi-square, Kruskal-Wallis and Mann-Whitney tests. The significance level was set at 0.05. Results: Based on Landry and Manchester criteria, wound healing process in the two groups was not significant (p=0.125). There was no significant difference between mean wound size reduction and VAS in both treatment and control groups (p=0.253). Conclusion: Topical NF has no effect on the natural process of healing oral mucosal ulcers and reducing pain. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection. Flow cytometry was used to assess ex vivo T-cell immunophenotypes and intracellular Tumor necrosis factor (TNF)-α/interferon(IFN)-γ/interleukin(IL)-2 following SARS-CoV-2-Spike-peptide stimulation. Comparisons were made using Wilcoxon signed-rank test for paired variables and Mann–Whitney for unpaired. In PLWH, Spike-specific CD4 T-cell frequencies plateaued post-2nd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. PLWH had higher frequencies of TNFα+CD4 T-cells and lower frequencies of IFNγ+CD8 T-cells than seronegative participants post-3rd dose. Regardless of HIV status, an increase in naive, regulatory, and PD1+ T-cell frequencies was observed post-3rd dose. In summary, two doses of SARS-CoV-2 vaccine induced a robust T-cell immune response in PLWH, which was maintained after the 3rd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. [ABSTRACT FROM AUTHOR]

The aim of this study is to obtain knowledge about which cultivable bacterial species are present in indoor air in homes, and whether the concentration and diversity of airborne bacteria are associated with different factors. Measurements have been performed for one whole year inside different rooms in five homes and once in 52 homes. Within homes, a room-to-room variation for concentrations of airborne bacteria was found, but an overlap in bacterial species was found across rooms. Eleven species were found very commonly and included: Acinetobacter lowffii, Bacillus megaterium, B. pumilus, Kocuria carniphila, K. palustris, K. rhizophila, Micrococcus flavus, M. luteus, Moraxella osloensis and Paracoccus yeei. The concentrations of Gram-negative bacteria in general and the species P. yeei were significantly associated with the season with the highest concentrations in spring. The concentrations of P. yeei, K. rhizophila and B. pumilus were associated positively with relative humidity (RH), and concentrations of K. rhizophila were associated negatively with temperature and air change rate (ACR). Micrococcus flavus concentrations were associated negatively with ACR. Overall, this study identified species which are commonly present in indoor air in homes, and that the concentrations of some species were associated with the factors: season, ACR and RH. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-related diarrhea reduces patients' quality of life and sometimes changes or interrupts their treatment regimen. This study aimed to evaluate the effect of yogurt with probiotics on diarrhea caused by chemotherapy. Method: The present study was a randomized controlled clinical trial. The sample consisted of 66 patients with colorectal cancer, recruited with convenience sampling method from patients who were referred to Buali Hospital of Tehran. The samples were randomly divided into three groups. The first group received yogurt with probiotics, the second group received yogurt alone, and the third group of control did not use yogurt during treatment. Data were gathered using the diarrhea section of adverse events. The number of defecations, the severity of diarrhea, and the consistency of stool in the seven days of the intervention were compared among the three groups. Analysis of variance and Tukey's post hoc test were performed through SPSS software. Results: The number of defecations in the yogurt group with probiotics and yogurt was significantly lower than the control group (P < 0.05). The severity of diarrhea in the yogurt group with probiotics decreased more rapidly (P < 0.05). Stool consistency in the yogurt group with probiotics was significantly better than the control group (P < 0.05). Conclusion: Based on the results of the present study, yogurt with probiotics can reduce and improve diarrhea caused by chemotherapy. The results also showed that yogurt alone can reduce diarrhea and improve its symptoms. [ABSTRACT FROM AUTHOR]

Pulmonary dysbiosis may predispose people living with HIV (PLWH) to chronic lung disease. Herein, we assessed whether intrapulmonary HIV reservoir size and immune disruption are associated with reduced bacterial lung diversity in PLWH. Bacterial DNA was extracted and PCR-amplified from cell-free bronchoalveolar lavage (BAL) fluid from 28 PLWH and 9 HIV-negative controls. Amplicon sequence variant (ASV) relative abundances and taxonomic identities were analyzed using joint species distribution modeling. HIV-DNA was quantified from blood and pulmonary CD4+ T-cells using ultra-sensitive qPCR. Immunophenotyping of BAL T-cells was performed using flow cytometry. Lung microbiome diversity was lower in smokers than non-smokers and microbiome composition was more variable in PLWH than HIV-negative individuals. Frequencies of effector memory BAL CD4+ and CD8+ T-cells positively correlated with abundance of several bacterial families while frequencies of BAL activated CD4+ T-cells negatively correlated with abundance of most lung bacterial families. Higher HIV-DNA levels in blood, but not in BAL, as well as frequencies of senescent CD4+ T-cells were associated with reduced bacterial diversity. These findings suggest that HIV infection may weaken the relationship between the lung microbiome and smoking status. Viral reservoir and immune activation levels may impact the lung microbiome, predisposing PLWH to pulmonary comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients.Methods: In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients.Results: A total of 654 patients (51.73 ± 15.12 years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6 mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment.Conclusion: The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens.Trial Registration: Clinicaltrials.gov identifier: NCT04460079. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders. [ABSTRACT FROM AUTHOR]

Objectives: Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied. Methods: Subsets of FoxP+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21). Results: Acute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP+ CD8 T-cells. We observed an increase in FoxP+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals. Conclusions: Although early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP+ CD8 T-cell, which may contribute to immune dysfunction. [ABSTRACT FROM AUTHOR]

Background: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2–positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. Methods: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. Results: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (− 0·03 [95% CI − 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. Conclusions: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups. [ABSTRACT FROM AUTHOR]

Background: Hypertension is one of the most common chronic diseases in the world. The prevalence of hypertension in the elderly is increasing. Patients with high blood pressure have to take medication throughout their lives. In this study, the relationship between antihypertensive drugs and oral health-related quality of life in the elderly was evaluated. Methods: This modified cross-sectional study, which is the part of the second phase of the Amirkola Health and Ageing Project (AHAP), was performed on 900 elderly people. Participants included 300 people with hypertension under medical treatment, 300 people with hypertension without medication and 300 people with normal blood pressure. All patients' blood pressure was recorded, and the standard xerostomia questionnaire and GOHAI questionnaire (Geriatric Oral Health Assessment Index) was completed for all participants. Then, the obtained data were analyzed by SPSS 17, whereby student's t-test, ANOVA and chi square, Pearson correlation coefficient and logistic regression model were used. A p<0.05 was considered statistically significant. Results: The mean GOHAI score in the three studied groups: hypertensive under medication treatment, hypertensive without medication treatment and normal blood pressure (51.1±7.4, 51.7±7.3, 51.1±7.5, respectively) did not differ significantly (P=0.533). The frequency of xerostomia was significantly different in the three groups (P=0.008). Among the antihypertensive drugs, the highest rate of xerostomia was due to the use of calcium channel blockers (31.1%) and diuretics (26.8%). Conclusion: In our study, although antihypertensive medications were associated with xerostomia, they did not decrease the oral health-related quality of life. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Molar teeth with furcation involvement are one of the most common problems in patients with periodontal disease. Regeneration methods are of the most controversial treatment strategies for these lesions. Purpose: The purpose of this study was to determine the effect of plasma rich in growth factors (PRGF) with 1.2% Atorvastatin (ATV) in the treatment of furcation involvement of mandibular molars. Materials and Method: The present randomized clinical trial was conducted on 15 patients with moderate periodontitis and class II furcation involvements; 24 defects were located in four groups of six, including debridement, ATV1.2%, PRGF, PRGF with ATV1.2%. The parameters of vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival index (GI), horizontal probing depth (HPD) and gingival recession (GR) were measured at baseline (T0), immediately before surgery (T1), 3 (T2), and 6 (T3) months after surgery. Moreover, the bone conditions were evaluated by digital subtraction radiography before and six months after surgery. Data were analyzed using SPSS23 software. Results: No significant difference in radiographic parameters was observed among the groups (p= 0.08). There was no significant difference in the mean levels of VPD, VCAL and HPD among the groups at different times (p<0.05). Comparison of clinical parameters of VPD, VCAL and GI in the treatment groups compared to the baseline showed a significant improvement in each group (p< 0.05) but there was no significant difference among different groups (p< 0.05). Conclusion: The use of PRGF with ATV 1.2% in grade II furcation involvement in mandibular molars was effective in the improvement of clinical and radiographic parameters six months after treatment, but this effect revealed no difference in comparison with the other groups. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) often have worse health outcomes compared to HIV-uninfected individuals. We characterized PLWH followed at a tertiary care clinic in Montreal who acquired COVID-19 and described their outcomes during the first wave of the pandemic. A retrospective chart review was performed for PLWH followed at the Chronic Viral Illness Service with a positive COVID-19 nasopharyngeal PCR or symptoms suggestive of COVID-19 between 1 March and 15 June 2020. Data on demographics, socioeconomic status, co-morbidities and severity of COVID-19 and outcomes were extracted. Of 1702 individuals, 32 (1.9%) had a positive COVID-19 test (n = 24) or symptoms suspicious for COVID-19 (n = 3). Median age was 52 years [IQR 40, 62]. Nearly all (97%) earned $34,999 Canadian dollars or less. Eleven (34%) individuals worked in long-term care (LTC) homes while 5 (6%) lived in LTC homes. Median CD4 count was 566 cells/mm3 [347, 726] and six had detectable plasma HIV viral loads. Median duration of HIV was 17 years [7, 22] and 30 individuals had been prescribed antiretroviral therapy. Five persons were asymptomatic. Of symptomatic persons, 21 (12%), 1 (4%) and 3 (12%) individuals had mild, moderate and severe disease, respectively. Three individuals died with COVID-19. In one case, the cause of death was due to COVID-19, whereas in the other two cases, the individuals died with positive COVID-19 test results but the immediate cause of death is unclear. PLWH who tested positive for COVID-19 had low socioeconomic status and had employment or living conditions that put them at high risk. PLWH may be disproportionately impacted by the social determinants of health which predispose them to COVID-19. [ABSTRACT FROM AUTHOR]

Despite the success of antiretroviral therapy (ART), people living with HIV continue to suffer from high burdens of respiratory infections, lung cancers and chronic lung disease at a higher rate than the general population. The lung mucosa, a previously neglected HIV reservoir site, is of particular importance in this phenomenon. Because ART does not eliminate the virus, residual levels of HIV that remain in deep tissues lead to chronic immune activation and pulmonary inflammatory pathologies. In turn, continuous pulmonary and systemic inflammation cause immune cell exhaustion and pulmonary immune dysregulation, creating a pro-inflammatory environment ideal for HIV reservoir persistence. Moreover, smoking, gut and lung dysbiosis and co-infections further fuel the vicious cycle of residual viral replication which, in turn, contributes to inflammation and immune cell proliferation, further maintaining the HIV reservoir. Herein, we discuss the recent evidence supporting the notion that the lungs serve as an HIV viral reservoir. We will explore how smoking, changes in the microbiome, and common co-infections seen in PLWH contribute to HIV persistence, pulmonary immune dysregulation, and high rates of infectious and non-infectious lung disease among these individuals. [ABSTRACT FROM AUTHOR]

Background and Objective: Periodontal disease is one of the most common chronic oral diseases worldwide. A variety of foods may affect periodontal health. Due to the importance of periodontal health in the old age, this study was designed to investigate the association between carbohydrate intake and periodontal health in the elderly in Amirkola, northern Iran. Methods: This cross-sectional study is part of the second phase of the Amirkola Health and Ageing Project (AHAP). The evaluated participants included 400 elderly people (200 men and 200 women). Socio-demographic data of all subjects were recorded in the information form. Periodontal status, including plaque index (PI), periodontal disease index (PDI) and Oral Hygiene Index (OHI) were evaluated. Then, the Semi-Quantitative Food Frequency Questionnaire (SQFFQ) was completed in order to receive daily carbohydrates in grams per day for all Participants. Then, the relationship between carbohydrate intake and periodontal health was evaluated. Findings: The participants consumed an average of 316±102.4 gr/day carbohydrates. The mean range of PI, OHI, PDI and in the high carbohydrate intake (>300 gr) group were 2.18±1.39, 2.84±1.51 and 1.51±0.86, respectively, and this rate was lower than the group with low carbohydrate intake (<300 gr) (1.96±1.52, 2.56±1.53 and 1.37±0.91), but the difference between the two groups was not significant. Conclusion: In the present study, there was no relationship between periodontal health indices and carbohydrate intake. [ABSTRACT FROM AUTHOR]

Background and Objective: Periodontal disease is one of the most common chronic oral diseases worldwide. A variety of foods may affect periodontal health. Due to the importance of periodontal health in the old age, this study was designed to investigate the association between carbohydrate intake and periodontal health in the elderly in Amirkola, northern Iran. Methods: This cross-sectional study is part of the second phase of the Amirkola Health and Ageing Project (AHAP). The evaluated participants included 400 elderly people (200 men and 200 women). Socio-demographic data of all subjects were recorded in the information form. Periodontal status, including plaque index (PI), periodontal disease index (PDI) and Oral Hygiene Index (OHI) were evaluated. Then, the Semi-Quantitative Food Frequency Questionnaire (SQFFQ) was completed in order to receive daily carbohydrates in grams per day for all Participants. Then, the relationship between carbohydrate intake and periodontal health was evaluated. Findings: The participants consumed an average of 316±102.4 gr/day carbohydrates. The mean range of PI, OHI, PDI and in the high carbohydrate intake (>300 gr) group were 2.18±1.39, 2.84±1.51 and 1.51±0.86, respectively, and this rate was lower than the group with low carbohydrate intake (<300 gr) (1.96±1.52, 2.56±1.53 and 1.37±0.91), but the difference between the two groups was not significant. Conclusion: In the present study, there was no relationship between periodontal health indices and carbohydrate intake. [ABSTRACT FROM AUTHOR]

Background: Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) is involved in immune dysregulation during HIV infection. Niacin (vitamin B3) could control the excess of tryptophan depletion and represents a potential strategy to improve immune functions and CD4 count recovery in immunological non-responder HIV-infected individuals on antiretroviral therapy (ART). Methods: In the CTN PT006 phase 2 pilot randomized trial, 20 adults on ART with CD4 ≤ 350 cells/µl, despite an undetectable viral load (VL) for at least 3 months, received 2000 mg of extended-release (ER)-niacin orally once daily for 24 weeks. Side effects, VL, CD4/CD8 counts, lipid profile, T-cell activation and senescence, Tregs and Th17 cell frequencies, Kyn/Trp ratio, and levels of IL-6, IP-10, sST2, I-FABP, and LBP were assessed following ER-niacin treatment. Results: Thirteen participants completed the study. Treatment was interrupted in 4 patients due to loss of follow-up or personal reasons and 3 patients were discontinued due to comorbidity risks. All participants maintained a VL < 40 copies/ml, while ER-niacin did not affect CD4 and CD8 cell counts. Plasma levels of triglycerides, total, and LDL cholesterol significantly decreased, following ER-niacin treatment. ER-niacin also diminished Kyn plasma levels and slightly decreased CD4 T-cell activation. However, no improvement in CD8 subsets, Kyn/Trp ratio, Th17/Treg balance, and plasma inflammatory markers was observed. Conclusions: Although ER-niacin combined with ART was well-tolerated among immune non-responders and decreased plasma lipids, it did not improve systemic inflammation, Kyn/Trp ratio, and CD4 cell recovery. Overall, ER-niacin was not effective to overcome chronic inflammation in PLWH. [ABSTRACT FROM AUTHOR]

Statement of the Problem: The tunnel technique has shown promising results in treatment of gingival recession. Plasma rich in growth factors (PRGF) is considered effective for soft tissue regeneration since it is a rich source of growth factors. Purpose: This clinical trial aimed to assess the efficacy of PRGF along with the tunnel technique and connective tissue graft for treatment of gingival recession. Materials and Method: In this controlled clinical trial, 20 areas around anterior and posterior teeth in 3 patients with gingival recession were bilaterally selected. The tunnel technique was used with and without PRGF in the test and control groups, respectively (10 areas in each group). The keratinized gingival width (KGW), clinical attachment level (CAL), clinical probing depth (PD), cementoenamel junction (CEJ) to mucogingival junction (MGJ) distance, and the esthetic visual analog scale (EVAS) score were evaluated preoperatively and at 6 weeks and 3 months, postoperatively. The gingival recession width (RW) and vertical recession depth (VRD) were assessed preoperatively and at 2 weeks and 3 months, postoperatively. The pain visual analog scale (PVAS) score was measured at 1, 3 and 7 days, post-treatment and the healing index (HI) was measured at 1, 3 and 7 days and 1 month, postoperatively. The root coverage percentage was assessed during 3 months. Paired t-test and repeated measures ANOVA were used for statistical analyses. p Value< 0.05 was considered statistically significant. Results: Significant improvements were noted in all tested parameters in both groups (p < 0.05). The mean root coverage percentage after 6 months was 88.68% ± 20.69% and 78.77% ± 24.94% in the test and control groups, respectively. None of the tested parameters were significantly different between the two groups (p > 0.05). Conclusion: Treatment of gingival recession with the tunnel technique can yield favorable clinical outcome, irrespective of the use/no use of PRGF. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) derived from periodontal ligament (PDL) and gingiva can be used for the development of cell-based regenerative approaches in dentistry and medicine. The purpose of this investigation was to establish a method for isolation of human stem cells from the PDL and gingiva, multilineage differentiation of those cells, and comparison of periodontal ligament mesenchymal stem cells (PDLMSCs) and gingival mesenchymal stem cells (GMSCs).Methods: PDL and gingival tissues of third molar teeth were digested enzymatically and the proliferative potential of human PDLMSCs and GMSCs was compared by MTT assay. The expression of cell surface epitopes was analyzed by flow cytometry. To investigate the multilineage differentiation capacity of these stem cells, osteogenic and adipogenic differentiation was achieved. The specific staining of nodules was performed to evaluate differentiation, whereas the expression of alkalin phosphatase (ALP) and collagen A I (COL I) genes was analyzed by quantitative real-time polymerase chain reaction.Results: The outgrown cells derived from PDL and gingival tissues were similar, fibroblast-like, and spindle-shaped. Further, the proliferation potential of GMSCs was greater than PDLMSCs. Both types of stem cells expressed MSC precursor markers, including CD73, CD90, and CD105, whereas they were negative for hematopoietic markers, including CD34 and CD45. PDLMSCs demonstrated more osteogenic potential compared to GMSCs with strong mineral noduls, and significantly greater expression of up-regulated bone-related markers ALP and COL I.Conclusion: MSCs derived from PDL and gingiva demonstrated multipotent characteristics, suggesting new therapeutic approaches in tissue engineering and PDLMSCs are more appropriate candidates for this purpose. [ABSTRACT FROM AUTHOR]

Introduction: Human papillomavirus (HPV) are the causative agent of mucosal neoplasia. Both cervical, anal and oropharyngeal cancers incidence is constantly increasing, making the HPV infection, a significant worldwide concern. Together, the CD8+ T cytotoxic cell-mediated response and the HPV-specific antibody response control most of the HPV infections before the development of cancers.Areas covered: We searched the MEDLINE and EMBASE databases and identified 228 eligible studies from 1987 to 2019 which examines both naturally acquired and vaccine induced humoral immunity against HPV infection in female and male subjects from worldwide origin. Herein, we synthesize current knowledge on the features of systemic and mucosal humoral immunity against HPV. We discuss the issues of the balance between the viral clearance or the escape to the host immune response, the differences between natural and vaccine-induced HPV-specific antibodies and their neutralizing capability. We also discuss the protection afforded after natural infection or following prophylactic vaccination.Expert opinion: Understanding the antibody response induced by HPV infection has led to the design of first-generation prophylactic vaccines. Now, prophylactic vaccination induces protective and long-lasting antibody response which would also strengthened the natural moderate humoral response in people previously exposed to the virus. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination. Objective: Our objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France. Methods: IgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea). Results: Fifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG. Conclusions: Around two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination. [ABSTRACT FROM AUTHOR]

Background Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH. Methods Cross-sectional and longitudinal assessments of plasma βDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and βDG-specific receptor expression on monocytes and natural killer (NK) cells. Results Plasma βDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). βDG increased over 24 months without ART but remained unchanged after 24 months of treatment. βDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid–binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated βDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively. Conclusions PLWH have elevated plasma βDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further βDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non–acquired immunodeficiency syndrome events. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Chronic periodontitis is a slow-growing inflammatory disease that often occurs in adults. In the elderly, periodontal indices may also change due to a number of psychological factors, such as depression and consequent changes in cortisol levels. Therefore, this study was performed to investigate the relationship between depression and periodontal indices in the elderly in Amirkola, Northern Iran. METHODS: This case-control study, which is part of the second phase of the Amirkola Health and Ageing Project (AHAP) to investigate the health status of the elderly in this city, was performed on 300 elderly people. After examination, subjects were divided into two groups: periodontitis (n=100) and control (n=200). In both groups, the presence of depressive symptoms was assessed using the Geriatric Depression Scale (GDS), in which a score of 5 or higher is a sign of depression, and periodontal indices including OHIS and PDI were examined based on PDI=4 periodontitis criterion. Then, the two groups were compared in terms of the association between periodontal indices and depression. FINDINGS: In this study, 133 were female (44.3%) and 167 were male (55.7%). 35 patients (35%) in the case group and 61 patients (30.5%) in the control group had symptoms of depression. The mean GDS score in patients with periodontitis (3.70±3.68) was slightly higher than healthy individuals (3.49±3.40), but no significant correlation was observed between GDS and PDI. Old age, male gender, lower level of education and smoking were higher in patients with periodontitis, which was statistically significant only in smoking and level of education (p=0.042 and p=0.009, respectively). In this study, a positive and weak relationship was observed between age and PDI (r=0.19 and p=0.001). CONCLUSION: The results showed that there is a relationship between periodontal indices and depression. Although it was not statistically significant, it is clinically noteworthy. [ABSTRACT FROM AUTHOR]

Background: Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH.Methods: Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers.Results: Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH.Conclusions: Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH. [ABSTRACT FROM AUTHOR]

Background. This study aimed to evaluate the effect of acellular dermal matrix allograft (ADMA) for the treatment of gingival recession as a substitute for subepithelial connective tissue graft (SCTG). Methods. In this controlled clinical trial, 18 teeth were selected in nine subjects with bilateral gingival recession. One side was treated with SCTG and a coronally displaced flap as the control group, and the other side was treated with ADMA and a coronally displaced flap as the test group. Probing pocket depth (PPD), clinical attachment level, vertical recession depth, recession width, gingival thickness, keratinized tissue width, and the root coverage percentage were measured before the surgery and at, -1 -3, and -6 month postoperative intervals. The healing index, pain index, and patient satisfaction were also investigated. The data were analyzed with a general linear model (GLM) repeated measures and paired t-test. Results. All the parameters improved except for PPD; however, a comparison between the groups did not reveal statistically significant differences. Only root coverage percentage and pain index were significantly lower in the test group. The average percentage of root coverage in the control and test groups were %16.62±82.01 and %9.4±64.44, respectively. Conclusion. Both methods resulted in improvements in the clinical results. However, the use of the ADMA led to less pain and root coverage in comparison with the SCTG method. [ABSTRACT FROM AUTHOR]

Background: Nowadays, one criterion to assess the impact of various treatments in cancer patients is the quality of life (QOL), which represents the patients' physical and psychosocial manner. It is already proved that BCc1 nanomedicine enjoys therapeutic behavior in cancer treatment of in vitro, animal, and human studies. Objectives: In the present study, we aimed at investigating the QOL in gastric cancer patients according to the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire after treating them with BCc1 nanomedicine synthesized based on nanochelating technology. Methods: A randomized, double-blind, and multicenter study was conducted to investigate the QLQ-STO30 of 60 metastatic (8 weeks after treatment) and 60 non-metastatic (20 weeks after treatment) gastric cancer patients in two separate groups named BCc1 nanomedicine and placebo. Results: In the metastatic patients, the mean difference of overall QLQ-STO30 showed a 2.8-score improvement in BCc1 nanomedicine (P < 0.05) and a 5.2-score decline in placebo (P < 0.05); in non-metastatic patients, it showed a 2.3-score improvement in BCc1 nanomedicine (P > 0.05) and a 3-score decline in placebo (P > 0.05). Conclusions: The results of the study showed that BCc1 nanomedicine improves a number of indices in metastatic and nonmetastatic gastric cancer patients, such as functional domains, symptom scales, and global QOL included in EORTC QLQ-STO30 questionnaire. [ABSTRACT FROM AUTHOR]

Background: Cancer is still the most common cause of morbidity in the world. Chitosan, a commonly used natural polymer, is consisted of different molecular weight with different biological activities. The purpose of this study was to determine cytotoxicity effect of high molecular weight (HMWC) and low molecular weight of chitosan (LMWC) on three cancerous cell lines MCF-7, HeLa and Saos-2 with different histological origin. Methods: The anticancer property of two types of chitosan on three cancerous cell lines and human fibroblast as normal cell line, was evaluated by cytotoxic activity including their apoptosis induction properties. Chitosan solutions 2% (w/v) were prepared. The cells were treated by different concentration of chitosan and viability was determined by MTT assay after 24, 48 and 72 h .Also the mode of cell death-apoptosis vs necrosis, was determined by Annexin V staining assay and analyzed by flow cytometry. Results: While both types of chitosan were effective in inhibiting cell proliferation of three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. Despite of a significant decrease in all 3 cell lines viability, up to 90%, but we didn't see a concentration dependent difference between both types of chitosan (HMWC and LMWC) in their cytotoxic effects. Flow cytometry analysis showed necrosis more observable with MCF7 while the apoptosis pattern of death was more in Saos-2 and HeLa. Also, higher viability with both types of chitosan was seen in fibroblast as normal cells. Conclusion: While chitosan is compatible with normal diploid fibroblast cells, it shows anticancerous effect against 3 cancerous cell lines. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property. [ABSTRACT FROM AUTHOR]

Context: One of the common oral bacterial infectious diseases is dental caries. Control of dental plaque formed by Streptococcus mutans and Streptococcus sobrinus leads to prevention and treatment of caries. Chitosan (1-4, 2-amino-2-deoxy-b-D-glucan), a deacetylated derivative from chitin, is an antimicrobial polysaccharide that exerts broad-spectrum activity against pathogenic bacteria and has been suggested as a preventive and therapeutic material for dental caries. Aim: The aim of this investigation is whether chitosan has effective antimicrobial and antibiofilm properties against common cariogenic microorganisms. Materials and Methods: The effect of 0.019–5 mg/ml of high-molecular-weight (HMW) and low-molecular-weight (LMW) chitosan on S. mutans and S. sobrinus was evaluated, and minimal inhibitory concentration (MIC) and minimal bactericide concentration (MBC) were determined. In addition, the effects of HMW and LMW of chitosan on bacterial adhesion to surfaces and biofilm formation were assayed by tube method. Results: The results showed that chitosan is capable of inhibiting S. mutans and S. sobrinus growth (P = 0.001). MIC of HMW chitosan for S. mutans and S. sobrinus was 0.62 mg/mL and MIC of LMW chitosan for S. mutans and S. sobrinus was 0.62 mg/mL, 1.25 mg/mL, respectively. MBC of HMW chitosan for S. mutans and S. sobrinus was 1.25 mg/mL, respectively, and MBC of LMW chitosan for S. mutans and S. sobrinus was 1.25 and 2.5 mg/ml, respectively. On the other hand, HMW chitosan was more effective than LMW chitosan. In addition, S. mutans showed equal MIC and MBC values for both MWs chitosan, but S. sobrinus was more resistant to LMW chitosan. Regarding biofilm growth, chitosan inhibited S. mutans and S. sobrinus adhesion and biofilm formation. The results of tube test showed weak adherence and biofilm formation in concentration of 0.312 and 0.625 mg/ml, but 1.25 and 2.5 mg/ml concentrations of both MWs could completely inhibit biofilm formation. Conclusion: These results display the potential of chitosan to be used as an effective antibacterial and antibiofilm agent for oral hygiene and health care. [ABSTRACT FROM AUTHOR]

Introduction Despite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome. Methods and analysis Twenty-six people living with HIV having undetectable viral load for at least 3 years will be randomised to receive TN-TC11LM (THC:CBD in 1:1 ratio) or TN-TC19LM (THC:CBD in 1:9 ratio) capsules daily for 12 weeks. Safety and tolerability of these capsules will be assessed through haematological, hepatic and renal blood tests, face-to-face interviews and questionnaires. Proportions of participants without any signs of significant toxicity (grades 0-2 scores on the WHO toxicity scale) and who complete the study, as well as scores on quality of life and mood will be examined using descriptive statistics. The effects on inflammatory markers, markers of peripheral blood reservoir size and effect on the composition of the gastrointestinal microbiome will be assessed before and after study completion. Ethics and dissemination This study has been approved by the Research Institute of the McGill University Health Centre. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open-access journal within 6 months of study completion. [ABSTRACT FROM AUTHOR]

Background. The ultimate aim of periodontal treatment is to regenerate periodontium and regenerative treatment after that. The aim of this study was to evaluate the effect of PRGF with 1% metformin biofilm in the treatment of two-wall intrabony periodontal defects. Methods. In this clinical trial, 8 patients with moderate chronic periodontitis and two-wall intrabony defect were selected. The defects were assigned to 4 groups: debridement, 1% metformin, PRGF, PRGF and metformin. The parameters of vertical probing depth, vertical clinical attachment level and gingival index were measured at baseline, immediately before surgery, and 3 and 6 months after surgery. In addition, the radiographic changes were evaluated with digital subtraction radiography before and 6 months after surgery. Analysis of the results was performed with repeated measurements, Friedman test and chisquared test. Results. All the groups exhibited improvements in all the clinical parameters after 6 months. Inter-group comparison of GI, CAL and PPD parameters revealed no statistically significant differences. Radiographic changes in the group of 1% metformin with PRGF revealed statistically significant differences compared with other groups; however, there were no statistically significant differences in other groups. Conclusion. Application of PRGF with 1% metformin in intrabony two-wall periodontal defects was effective in improving the clinical parameters but this effect revealed no difference compared with other groups; however, in terms of radiographic changes significant improvements were noted [ABSTRACT FROM AUTHOR]

HIV persists in tissues during antiretroviral therapy (ART), but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We performed an extensive characterization of HIV reservoirs in two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA is detected in all tissues, with large variations across anatomical compartments and between participants. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are common in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells expand, migrate, and possibly circulate between anatomical sites. [Display omitted] • In people on ART, half the HIV genomes in tissues are clonally expanded • Genetically intact HIV proviruses are more often found in lymphoid tissues • Identical proviral sequences are frequently found in distant tissues Dufour et al. study viral reservoirs by analyzing multiple samples from two men who donated their bodies for HIV cure research. They show that genetically intact proviruses are more often found in lymphoid organs. Moreover, half of the HIV genomes in tissues are clonally expanded and are frequently located in distant compartments. [ABSTRACT FROM AUTHOR]