Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection

IntroductionSemen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.MethodsWe assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits.ResultsHere, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021).ConclusionsMore recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women.     

The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states

We estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

     

Qualité des supports de communication de crise lors de la pandémie de la COVID-19 au Grand Maghreb

ObjectiveTo objectively assess the quality of “crisis communication” media, during the COVID-19 pandemic, in the three Greater Maghreb countries (Tunisia, Algeria, Morocco).MethodsA compliance audit for press releases and epidemiological bulletins was analyzed against a quality benchmark, which had been specifically designed by the authors. This framework, made up of five dimensions and 50 items, graded (0/1), was applied by two researchers in preventive medicine. Multiplying the scores by a coefficient of two resulted in a partial score of 20 points for each dimension and a total score of 100 points for the checklist taken as a whole. The quality of the communication media was considered to be good when exceeding the thresholds of 15/20 for the different dimensions and 75/100 for the entire grid.ResultsA total of 141 information media were included in this audit (Tunisia: 60; Algeria: 60; Morocco: 21). The overall median quality score for these media was only 56/100 (IIQ: [46–58]), without major variability between countries. The most appreciated dimension was “maintaining the confidence of the population”, with an overall median score of 14/20 (12/20 for epidemiological bulletins and 16/20 for press releases). The most poorly rated dimension was “strengthening community participation”, with a median score of only 4/20 (6/20 for epidemiological bulletins and 4/20 for press releases).ConclusionThe quality of the Maghreb crisis communication media during COVID-19 was insufficient in most of its dimensions and items, particularly from a psychosocial standpoint. Reinforcement of the capacities of communication officers to develop information material and supports during health crises is indispensable and should be considered as an urgent matter.     

The cell cycle and induction of apoptosis in a hamster fibrosarcoma cell line treated with anti-cancer drugs: Its importance to solid tumour chemotherapy*

The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1--D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea, 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exp osure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G₀/G₁, S and G₂/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G₀/G₁ phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G₂/M phase cells more susceptible to actinomycin D, 1--D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G₂/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G₂/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design.     

Induction of a low voltage-activated,fast-inactivating Ca2+ channel in cultured bone marrow stromal cells by dexamethasone

The production of biochemical markers associated with the osteoblastic phenotype, and accompanying changes in the expression of voltage-operated Ca²⁺ channels, have been examined in rat bone marrow stromal cell cultures treated with dexamethasone (10^-8 M). Whole cell clamp analysis of voltage-operated Ca²⁺ channels in control cultures (using Ba²⁺ as the charge carrier) revealed primarily a high voltage-activated (HVA), slowly inactivating current, which was enhanced two- to threefold by treatment of the cells with Bay K 8644 (300 nM) and inhibited by nifedipine (4 M). In dexamethasone-treated cultures, the I–V relationship for inward current was shifted to more positive potentials in comparison with control cells. Most cells in these cultures possessed both the HVA current and also a faster inactivating, low-voltage-activated (LVA), nifedepineresistant current. These two currents could be separated both by nifedipine and by the use of steady state inactivation of the LVA current. The two components of the Ba²⁺ current varied widely in their relative size. The combination of LVA and HVA currents seen in dex-induced stromal cells resembles records of voltage-operated Ca²⁺ channels from cultures of calvarial osteoblasts.     

Doppler sonographic parameters for detection of carotid stenosis: is there an optimum method for their selection?

OBJECTIVE: A wide range of Doppler threshold values for carotid stenosis is found in the literature. We undertook this study to compare methods of derivation and to determine if an optimum strategy of threshold selection exists for a high-risk population. MATERIALS AND METHODS: From the sonograms of all patent internal carotid arteries, peak systolic velocity in the internal carotid artery (ICA(PSV)) and the ratio of peak systolic velocity in the internal carotid artery to that of the common carotid artery (ICA(PSV)/ CCA(PSV)) were compared with the percentage of angiographically determined stenosis. Receiver operating characteristic curves were generated for levels of stenosis > or =60% and > or =70%. Doppler thresholds were chosen on the basis of maximum accuracy and on the basis of > or =90% sensitivity and specificity. Patients were then segregated into symptomatic and asymptomatic cohorts, and the above process was repeated. An effectiveness analysis was also conducted using various Doppler thresholds. Thresholds derived using these three methods were compared and optimal values chosen. RESULTS. Of 333 carotid arteries that fit inclusion criteria, 132 were found in asymptomatic patients and 201 in symptomatic patients. Maximum accuracy, > or =90% sensitivity and specificity, and effectiveness analysis each produced different ranges of thresholds. We chose final thresholds that maintained patient outcome profiles. For asymptomatic patients at the > or =60% stenosis level, thresholds were ICA(PSV) = 200 cm/sec and ICA(PSV)/CCA(PSV) = 3.0. For symptomatic patients with stenosis > or =70%, thresholds were ICA(PSV) = 175 cm/sec and ICA(PSV)/CCA(PSV) = 2.5. CONCLUSION: Considerable latitude exists in the choice of carotid Doppler thresholds. We propose a rational strategy for threshold selection based on a combination of three commonly used methods. Our observations indicate that it appears advisable to consider symptomatic and asymptomatic patients separately and to apply appropriately derived thresholds.     

Influence of surgery on renal amyloidosis

It is well known that renal amyloidosis (RA) leads to ESRD in a few years. This evolution may be accelerated by several factors such as steroids, renal vein thrombosis, infections or surgery. We report 22 patients (14M,8F) mean age = 41.6 years (13-72) with RA in whom surgery revealed or aggravated renal disease. The group I includes 15 patients with no previous history of renal disease and who developed oedema few days after surgery with acute renal failure in 5 of them. Proteinuria was present in all the cases with a nephrotic syndrome in 10. Percutaneous kidney biopsy (KB) showed renal amyloidosis in all patients (AA+ = 8 cases, AA- = 3 cases). Only 9 patients were followed-up (mean period = 40 months): 2 patients are stationary; 1 is on complete remission 2 are on HD and 4 died. The group II includes 7 patients with a previous history of nephropathy (Histologically proven amyloidosis: 3 CRF = 1, Oedema: 3). All these patients developed oedema few days after surgery with acute RF in 4 patients. KB performed in all of them showed RA (AA+ = 33, AA- = 1). 6 patients were followed up for a mean period of 11 months: 5 died, 1 patient is on HD. The influence of surgery on renal amyloidosis is often unforeseeable. It may have no effect on renal disease, but very often it reveals RA and sometimes dramatically aggravates the course of the disease with occurrence of irreversible CRF. The pathogenic role of surgery on RA is discussed.