Short communication: NKG2C+ NK cells contribute to increases in CD16+CD56- cells in HIV type 1+ individuals with high plasma viral load.

Chronic HIV-1 infection results in the expansion of both NKG2C+ and CD16+CD56- human natural killer cells. NKG2C+ cells proliferate in response to human cytomegalovirus (HCMV) and expansion of the dysfunctional CD56-CD16+ natural killer (NK) cells is associated with HIV-1 viremia. Here we report an association between increased proportions of CD56-CD16+ NK cells in viremic HIV-1+ individuals and an increased contribution of NKG2C+ cells to this subset. These data, in addition to anti-HCMV IgG serology, indicate a potential contribution of both HCMV and HIV-1 to NK cell dysfunction in HIV-1-infected individuals

Quality of Work Life (QoWL) and Perceived Workplace Commitment among Seasonal Farmers in Nigeria

This study set out to research the impact of Quality of Work Life (QoWL) in Low- and Middle-Income Countries (LMICs) and the perception of farm workers regarding how both intrinsic and extrinsic control elements within and outside the work setting impact their productivity within the farming industry in Nigeria. To our knowledge, this is the first study that has considered QoWL among farm workers in Nigeria. Farm workers in the Middle Belt region in Nigeria (n = 435) were surveyed using a QoWL questionnaire consisting of 32 Likert scale items to measure their perceived quality of work life based on seven dimensional factors. Results indicated that more than half (60.6%) of the sampled group confirmed working far above the national working hours of 40 h per week. Significant differences exist between respondent gender on control at work (CAW) (F = 10.03, p < 0.001) and working conditions (WCS) (F = 12.04, p < 0.001), with women having better QoWL. Farm worker job satisfaction, especially in LMICs, is an important element that can lead to high productivity and sustainability of the sector. To achieve a level of sustainability and food security in Nigeria, there is the need to improve opportunities for greater stability among farmers. Farm workers could benefit from tailored training initiatives around stress management and work–life balance, as well as workplace safety nad health and wellbeing as a means of boosting their confidence and enhance sustainable productivity. In addition, this paper holds the potential to inform framework development for assessing QoWL within the farming industry in Nigeria and encourage further research around the impact of job insecurity on the nation’s food security

Assessment of Workplace Safety Climate among Health Care Workers during the COVID-19 Pandemic in Low and Middle Income Countries- Case Study of Nigeria

The COVID-19 pandemic has presented several organizations with the opportunity to review their operational strategies, as well as the existing safety climate within their establishments. The healthcare sector is not an exception, especially those in Low and Middle Income Countries (LMICs), where most safety systems are not robust when compared with developed countries. The study aim is to assess the occupational safety climate among healthcare workers (HCWs) in LMICs using Nigeria as a case study. A cross-sectional study was adopted to measure safety climate perception among professionals working in healthcare establishment during the COVID-19 pandemic using a validated Nordic Safety Climate Questionnaire (NOSACQ-50). At the end of the survey period, 83% (433) of the responses were adjudged to have met the threshold criteria and were used to inform the study outcome. Worker safety commitment within the healthcare facilities (M = 3.01, SD = 0.42) was statistically significantly higher than management safety priority, commitment, and competence (M = 2.91, SD = 0.46), t(130.52), p < 0.001. A significant effect of the management role was found in regards to management safety priority, commitment, and competence (F(1, 406) = 3.99, p = 0.046, η2 = 0.010). On the contrary, the managerial position does not have a significant effect on worker safety commitment (F(1, 417) = 0.59, p = 0.440, η2 = 0.001). The outcome from the study showed that, where there is active promotion of a positive safety climate in healthcare sectors in LMICs, employees are more likely to engage in positive safety behaviour. To help address the identified gaps, there is the need for more effort to be made towards promoting an effective and positive safety climate across the establishment, including management and healthcare worker commitment

RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Depletion of natural killer cells in the colonic lamina propria of viraemic HIV-1-infected individuals.

BACKGROUND: HIV-1 infection is known to have a detrimental impact on peripheral blood natural killer cell phenotype and function. Chronic HIV-1 also causes a substantial depletion of CD4+ T cells in the gastrointestinal tract and the blood. OBJECTIVE: To investigate the impact of chronic HIV-1 infection with on natural killer cell populations in the gastrointestinal tract and the effect of suppression of plasma viraemia with antiretroviral therapy. METHODS: Lymphocyte populations were extracted from the lamina propria of biopsies taken from the sigmoid colon of HIV-1-infected and uninfected individuals. The proportions of natural killer cell subsets were compared in viraemic (n = 15) and aviraemic HIV-1-positive, HAART-treated individuals (n = 27) and HIV-1 negative control individuals (n = 26) using flow cytometry on gated subsets. RESULTS: Natural killer cells are depleted in colonic biopsies from HIV-1-infected individuals with detectable plasma virus in comparison with HIV-1-negative individuals. A significant increase in the proportion of both natural killer and CD4+ T cells in the colonic lamina propria is observed in aviraemic individuals compared to viraemic individuals. CONCLUSIONS: Chronic HIV-1 infection results in depletion of both natural killer cells and CD4+ T cells in colonic tissue and antiretroviral therapy results in a recovery of these subsets in individuals with undetectable plasma viral load

Switch from inhibitory to activating NKG2 receptor expression in HIV-1 infection: lack of reversion with highly active antiretroviral therapy.

BACKGROUND: HIV-1 infection is characterized by increase in inhibitory receptors and loss of activating receptors on natural killer (NK) cells, resulting in loss of cell activity. Exceptionally, for an inhibitory receptor, the proportion of NK cells bearing CD94-NKG2A decreases during HIV-1 infection. It is not understood whether HIV-1 itself or other concomitant infections drive these changes. OBJECTIVES: To investigate the relationship between HIV-1 viraemia and changes in C-type lectin-like receptor expression in NK cells and to investigate the effect of highly active antiretroviral therapy (HAART) on these changes. METHODS: Three cohorts of patients were studied: (1) before, during and after treatment interruption in aviraemic and viraemic patients receiving HAART (n = 15); (2) HIV-1-positive treatment-naive individuals (n = 13); and (3) HIV-1-positive individuals receiving successful HAART for a minimum of 1 year without interruption (n = 11). Flow cytometry was used to study the expression of NKG2A before and after treatment interruption and to define expanded populations of NK cells in untreated and treated HIV-1-positive individuals. Assays were performed in vitro to assess the cytotoxicity of the expanded populations. RESULTS: Increases in plasma HIV-1 RNA during treatment interruption in aviraemic HAART-treated individuals did not influence the proportion of NK cells carrying the complex CD94-NKG2A. Loss of NKG2A NK cells corresponded to the dramatic expansion of a distinct population of cells expressing a functional activating CD94-NKG2C receptor with skewed expression of killer cell immunoglobulin-like receptor family and natural cytotoxicity receptors. CONCLUSION: Changes in the NK cell repertoire during HIV-1 infection were not a result of HIV-1 viraemia alone but resembled those associated with concomitant infections