Acceptability of extending HPV-based cervical screening intervals from 3 to 5 years: An interview study with women in England

Objectives: The introduction of primary HPV testing in the NHS Cervical Screening Programme in England means the screening interval for 25-49-year-olds can be extended from 3 to 5 years. We explored womens responses to the proposed interval extension. Methods: We conducted semi-structured phone/video interviews with 22 women aged 25-49 years. Participants were selected to vary in age, socioeconomics, and screening history. We explored attitudes to the current 3-year interval, then acceptability of a 5-year interval. Interviews were transcribed verbatim and analysed using Framework Analysis. Results: Attitudes to the current 3-year interval varied; some wanted more frequent screening, believing cancer develops quickly. Some participants worried about the proposed change; others trusted it was evidence-based. Frequent questions concerned the rationale and safety of longer intervals, speed of cancer development, the possibility of HPV being missed or cell changes occurring between screens. Many participants felt reassured when the interval change was explained alongside the move to HPV primary screening, of which most had previously been unaware. Conclusions: Communication of the interval change should be done in the context of broader information about HPV primary screening, emphasising that people who test negative for HPV are at lower risk of cell changes so can safely be screened every 5 years. The long time needed for HPV to develop into cervical cancer provides reassurance about safety, but it is important to be transparent that no screening test is perfect.

Escherichia coli chemotaxis to competing stimuli in a microfluidic device with a constant gradient

In natural systems bacteria are exposed to many chemical stimulants; some attract chemotactic bacteria as they promote survival, while others repel bacteria because they inhibit survival. When faced with a mixture of chemoeffectors, it is not obvious which direction the population will migrate. Predicting this direction requires an understanding of how bacteria process information about their surroundings. We used a multiscale mathematical model to relate molecular level details of their two-component signaling system to the probability that an individual cell changes its swimming direction to the chemotactic velocity of a bacterial population. We used a microfluidic device designed to maintain a constant chemical gradient to compare model predictions to experimental observations. We obtained parameter values for the multiscale model of Escherichia coli chemotaxis to individual stimuli, α-methylaspartate and nickel ion, separately. Then without any additional fitting parameters, we predicted the response to chemoeffector mixtures. Migration of E. coli toward α-methylaspartate was modulated by adding increasing concentrations of nickel ion. Thus, the migration direction was controlled by the relative concentrations of competing chemoeffectors in a predictable way. This study demonstrated the utility of a multiscale model to predict the migration direction of bacteria in the presence of competing chemoeffectors.

Influence of Prebiotic Activity of Agave salmiana Fructans on Mucus Production and Morphology Changes in Colonic Epithelium Cell of Healthy Wistar Rats

The beneficial health of evaluating prebiotic effect by the consumption of Agave salmiana fructans (A. salmiana fructans) was assessed in the epithelium of the cecum and proximal colon of Wistar rats fed at different doses for 35 days with regards to mucus production, morphological cell changes, and the serum concentration of tumor necrosis factor-α (TNF-α). Results showed a significant increase in mucus-secreting cells (P < 0.05) and a normal structure with preserved crypts, without morphological damage to colonic cells for a dose of 12.5% (w/w) with respect to the control and the other doses evaluated. The concentration of pro-inflammatory cytokine TNF-α was decreased significantly (P < 0.05) in the groups with doses of 10 and 12.5% (w/w) at 7 and 35 days, respectively. This effect was positively correlated with the reduction of inflammation in epithelial cells. This study provides direct evidence of the effects of the A. salmiana fructans on the colonic epithelium, demonstrating that a diet supplemented with 12.5% of fructans for 35 days exerts health benefits through the strengthening of the mucosa layer, which favors the adherence of the bacterial population and suppresses inflammation.

Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?

Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells.

Characterizing Sex Differences in Depressive-Like Behavior and Glial Brain Cell Changes Following Peripheral Nerve Injury in Mice

Chronic pain and depression are intimately linked; the combination of the two leads to higher health care costs, lower quality of life, and worse treatment outcomes with both conditions exhibiting higher prevalence among women. In the current study, we examined the development of depressive-like behavior in male and female mice using the spared nerve injury (SNI) model of neuropathic pain. Males displayed increased immobility on the forced-swim test – a measure of depressive-like behavior – 2 weeks following injury, while females developed depressive-like behavior at 3-week. Since the pathogenesis of chronic pain and depression may involve overlapping mechanisms including the activation of microglial cells, we explored glial cell changes in brain regions associated with pain processing and affect. Immunohistochemical analyses revealed that microglial cells were more numerous in female SNI mice in the contralateral ventral anterior cingulate cortex (ACC), a brain region important for pain processing and affect behavior, 2-week following surgery. Microglial cell activation was not different between any of the groups for the dorsal ACC or nucleus accumbens. Analysis of astrocyte density did not reveal any significant changes in glial fibrillary acidic protein (GFAP) staining in the ACC or nucleus accumbens. Overall, the current study characterized peripheral nerve injury induced depression-like behavior in male and female mice, which may be associated with different patterns of glial cell activation in regions important for pain processing and affect.

HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave

There are conflicting reports on the effects of HIV on COVID-19. Here we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.

T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease

Although advances in preventive medicine have greatly improved prognosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. This clearly indicates that there remain residual cardiovascular risks that have not been targeted by conventional therapies. The results of multiple animal studies and clinical trials clearly indicate that inflammation is the most important residual risk and a potential target for CVD prevention. The immune cell network is intricately regulated to maintain homeostasis. Ageing associated changes to the immune system occurs in both innate and adaptive immune cells, however T cells are most susceptible to this process. T-cell changes due to thymic degeneration and homeostatic proliferation, metabolic abnormalities, telomere length shortening, and epigenetic changes associated with aging and obesity may not only reduce normal immune function, but also induce inflammatory tendencies, a process referred to as immunosenescence. Since the disruption of biological homeostasis by T cell immunosenescence is closely related to the development and progression of CVD via inflammation, senescent T cells are attracting attention as a new therapeutic target. In this review, we discuss the relationship between CVD and T cell immunosenescence associated with aging and obesity.