The Effects of HIIT Versus MICT and Sedentary Controls on Blood Lipid Concentrations in Nondiabetic Overweight and Obese Young Adults: A Meta-analysis.

International Journal of Exercise Science 16(3): 791-813, 2023. With rates of obesity and dyslipidemia rising among young adults, this meta-analysis aimed to compare the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) and sedentary controls (CON) on low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC) in nondiabetic overweight and obese young adults to determine if HIIT or MICT is more efficacious in improving dyslipidemia. Studies included in the analysis had to be randomized controlled trials or quasi-experimental studies, comparing the effects of HIIT versus MICT or CON on at least three variables of interest: LDL, HDL, TG, and TC, in nondiabetic adults, with body mass indexes (BMIs) above 25, and average ages between 18-30. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. Eight studies fulfilled the selection criteria, with a mean PEDro quality score of 5.8. Compared to CON, HIIT significantly decreased the concentrations of LDL (-12.14 mg/dL, p = \u3c 0.00001) and TC (-9.27 mg/dL, p = 0.003), without significantly affecting HDL or TG. Compared to MICT, HIIT significantly decreased the concentrations of LDL (-6.23 mg/dL, p = 0.05) and TC (-7.85 mg/dL, p = 0.02), without significantly affecting HDL or TG concentrations. HIIT is superior to MICT and CON in improving the concentrations of LDL and TC in our target population. As early management of dyslipidemia improves long-term health, we recommend clinicians consider HIIT training protocols for their nondiabetic overweight and obese young adult patients

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma

BACKGROUND: Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10-15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy.MATERIALS AND METHODS: Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment.RESULTS: Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively.DISCUSSION: Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential

Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha

<p>Background: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation.</p> <p>Methods/Principle Findings: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-α treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-α stimulated hepatocyte lines were still able to present antigen and induce IFN-γ expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-α, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor–proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection.</p> <p>Conclusion/Significance: IFN-α induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.</p&gt

Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody

Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant

Hookworm-Related Anaemia among Pregnant Women: A Systematic Review

Anaemia affects large numbers of pregnant women in developing countries and increases their risk of dying during pregnancy and delivering low birth weight babies, who in turn are at increased risk of dying. Human hookworm infection has long been recognized among the major causes of anaemia in poor communities, but understanding of the benefits of the management of hookworm infection in pregnancy has lagged behind the other major causes of maternal anaemia. Low coverage of anthelmintic treatment in maternal health programmes in many countries has been the result. After systematically reviewing the available literature we observed that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women. We also estimate that between a quarter and a third of pregnant women in sub-Saharan Africa are infected with hookworm and at risk of preventable hookworm-related anaemia. However, all identified intervention studies showed a benefit of deworming for maternal or child health and we argue that increased efforts should be made to increase the coverage of anthelmintic treatment among pregnant women