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Dietary fibre in hypertension and cardiovascular disease management: systematic review and meta-analyses
Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure and other cardiometabolic risk factors. The extent to which dietary fibre can further reduce risk for those with CVD and treated with cardioprotective drugs has not been clearly established. We have examined the evidence for dietary fibre as adjunct therapy in those with CVD or hypertension.
Methods
Ovid MEDLINE, Embase, PubMed, and CENTRAL were searched to June 2021. Prospective observational studies reporting on fibre intakes and mortality in those with pre-existing CVD and controlled trials of increasing fibre intakes on cardiometabolic risk factors in those with CVD or hypertension were eligible. Outcomes were mortality (studies) and cardiometabolic risk factors (trials). Data synthesis was with random effects and dose response. Certainty of evidence was assessed using GRADE.
Results
Three prospective studies including 7469 adults with CVD, and 12 trials of 878 adults with CVD or hypertension were identified. Moderate certainty evidence indicates reduced all-cause mortality (relative risk, RR0.75 (95% confidence interval, CI 0.58–0.97)) when comparing higher with lower fibre intakes. Low certainty evidence from trials of adults with cardiovascular disease indicates increasing fibre intakes reduced total (mean difference, MD − 0.42 mmol/L (95%CI − 0.78 to − 0.05) and low-density lipoprotein (LDL) cholesterol (MD − 0.47mmol/L (95%CI − 0.85 to − 0.10)). High certainty evidence from trials of adults with hypertension indicates increasing fibre intakes reduces systolic (MD 4.3 mmHg (95% CI 2.2 to 5.8)) and diastolic blood pressure (MD 3.1 mmHg (95% CI 1.7 to 4.4)). Moderate and low certainty evidence indicated improvements in fasting blood glucose (MD 0.48 mmol/L (− 0.91 to − 0.05)) and LDL cholesterol (MD 0.29 mmol/L (95% CI 0.17 to 0.40)). Benefits were observed irrespective of cardioprotective drug use
Mutations of PI3K-AKT-mTOR pathway as predictors for immune cell infiltration and immunotherapy efficacy in dMMR/MSI-H gastric adenocarcinoma
A significant subset of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric adenocarcinomas (GAC) are resistant to immune checkpoint inhibitors (ICIs), yet the underlying mechanism remains largely unknown. We sought to investigate the genomic correlates of the density of tumor-infiltrating immune cells (DTICs) and primary resistance to ICI treatment.
Methods
Four independent cohorts of MSI-H GAC were included: (i) the surgery cohort (n = 175) with genomic and DTIC data, (ii) the 3DMed cohort (n = 32) with genomic and PD-L1 data, (iii) the Cancer Genome Atlas (TCGA) cohort (n = 73) with genomic, transcriptomic, and survival data, and (iv) the ICI treatment cohort (n = 36) with pre-treatment genomic profile and ICI efficacy data.
Results
In the dMMR/MSI-H GAC, the number of mutated genes in the PI3K-AKT-mTOR pathway (NMP) was positively correlated with tumor mutational burden (P < 0.001) and sensitivity to PI3K-AKT-mTOR inhibitors and negatively correlated with CD3+ (P < 0.001), CD4+ (P = 0.065), CD8+ (P = 0.004), and FOXP3+ cells (P = 0.033) in the central-tumor rather than invasive-margin area, and the transcription of immune-related genes. Compared to the NMP-low (NMP = 0/1) patients, the NMP-high (NMP ≥ 2) patients exhibited a poorer objective response rate (29.4% vs. 85.7%, P < 0.001), progression-free survival (HR = 3.40, P = 0.019), and overall survival (HR = 3.59, P = 0.048) upon ICI treatment
Potential for a Plant-Made SARS-CoV-2 Neutralizing Monoclonal Antibody as a Synergetic Cocktail Component
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, the current mAbs produced in mammalian cells are expensive and might be unaffordable for many. Furthermore, the emergence of variants of concern demands the development of strategies to prevent mutant escape from mAb treatment. Using a cocktail of mAbs that bind to complementary neutralizing epitopes is one such strategy. In this study, we use Nicotiana benthamiana plants in an effort to expedite the development of efficacious and affordable antibody cocktails against SARS-CoV-2. We show that two mAbs can be highly expressed in plants and are correctly assembled into IgG molecules. Moreover, they retain target epitope recognition and, more importantly, neutralize multiple SARS-CoV-2 variants. We also show that one plant-made mAb has neutralizing synergy with other mAbs that we developed in hybridomas. This is the first report of a plant-made mAb to be assessed as a potential component of a SARS-CoV-2 neutralizing cocktail. This work may offer a strategy for using plants to quickly develop mAb cocktail-based therapeutics against emerging viral diseases with high efficacy and low cost
Live Vaccination with Blood-Stage Plasmodium yoelii 17XNL Prevents the Development of Experimental Cerebral Malaria
In our work, we aim to develop a malaria vaccine with cross-strain (-species) protection. C57BL/6 mice infected with the P. berghei ANKA strain (PbA) develop experimental cerebral malaria (ECM). In contrast, ECM development is inhibited in infected mice depleted of T cells. The clinical applications of immune-cell depletion are limited due to the benefits of host defense against infectious diseases. Therefore, in the present study we attempted to develop a new method for preventing ECM without immune cell depletion. We demonstrated that mice inoculated with a heterologous live-vaccine of P. yoelii 17XNL were able to prevent both ECM and lung pathology and survived longer than control mice when challenged with PbA. Live vaccination protected blood–organ barriers from PbA infection. Meanwhile, live vaccination conferred sterile protection against homologous challenge with the P. yoelii 17XL virulent strain for the long-term. Analysis of the immune response induced by live vaccination showed that cross-reactive antibodies against PbA antigens were generated. IL-10, which has an immunosuppressive effect, was strongly induced in mice challenged with PbA, unlike the pro-inflammatory cytokine IFNγ. These results suggest that the protective effect of heterologous live vaccination against ECM development results from IL-10-mediated host protectio
Evaluation of the Real-World Effectiveness of Vaccines against COVID-19 at a Local Level: Protocol for a Test-Negative Case–Control Study
Vaccines against COVID-19 approved for use in the EU/EEA have been shown to be highly effective against wild-type SARS-CoV-2. However, their effectiveness against new variants may be reduced. This study aims to evaluate the effectiveness of vaccines against COVID-19 in the prevention of symptomatic and severe disease, during pre- and post-omicron phases. Individuals who sought treatment at the emergency department of a Portuguese hospital with COVID-19-like disease and were tested for SARS-CoV-2 are the subjects of the study. Patients who received a positive result are considered cases, while those with negative results are the controls. The test-negative case–control method is one of the study designs recommended by WHO to estimate the effectiveness of vaccines against COVID-19. The main advantage of this design is that it controls for the healthcare seeking bias, commonly present in traditional cohort and case–control designs. This study may have broad implications for understanding the real-world performance of the COVID-19 vaccines at the local level, which may play a key role in promoting adherence to vaccination. Moreover, this study may contribute to inform decisions regarding booster doses and variant-specific vaccine formulations leading to the control of this and future pandemic
Acceptance of COVID-19 Vaccines among Adults in Lilongwe, Malawi: A Cross-Sectional Study Based on the Health Belief Model
The COVID-19 pandemic has had a significant economic and social impact on Malawi. Promoting vaccination is a key protection measure against COVID-19. Employing the health beliefs model (HBM), this study explores various factors that influence COVID-19 vaccination acceptance (intentions and behavior) among adult residents of Malawi. A semi-structured questionnaire was used for data collection. A field-based survey was conducted among adult residents in Lilongwe, Malawi. Descriptive statistics, linear regression, the Chi-square test, and Pearson’s correlation statistics were used for data analysis. A total of 758 questionnaires were involved. Respondents aged 18–24 (OR = 5.079, 95% CI 2.303–11.202), 25–34 (OR = 2.723, 95% CI 1.363–5.438), urban residents (OR = 1.915, 95% CI 1.151–3.187), graduates/professionals (OR = 1.193, 95% CI 0.857–1.651), health workers (OR = 4.080, 95% CI 1.387–12.000), perceived susceptibility (OR = 1.787, 95% CI 1.226–2.605), perceived benefit (OR = 2.992, 95% CI 1.851–4.834), and action cues (OR = 2.001, 95% CI 1.285–3.115) were predictors for “acceptance of COVID-19 vaccine”. The health belief model structure can be used as a good predictor of vaccine acceptance, especially “perceived susceptibility,” “perceived benefit,” and “action cues”. Strengthening COVID-19 vaccine education in these areas will be an important future intervention
The Evaluation of the Neuroprotective Effect of a Single High-Dose Vitamin D3 in Patients with Moderate Ischemic Stroke
ntroduction. Vitamin D insufficiency is highly prevalent and is a negative predictor for survival in ischemic stroke patients. We evaluated the effect of a high dose of vitamin D3 on the Neuron-Specific Enolase (NSE) level, National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) scoring system in moderate ischemic stroke patients. Methods. This prospective, double-blind, randomized clinical trial (RCT) study was conducted from April 2020 to March 2021. Patients with moderate ischemic stroke (NIHSS 5 to 15) who had vitamin D deficiency (serum 25-OH vitamin D ≤30 ng/mL) were recruited and randomized into intervention and control groups. Subjects in the intervention group received a single dose, intramuscular (IM) injection of 600000 international unit (IU) vitamin D3, in addition to the standard treatment. NSE level and NIHSS were evaluated at baseline and 48 hours after the intervention. The BI was monitored three months after discharge. Results. During the study period, 570 patients were assessed; finally, forty-one patients completed the study. Except for the age which was higher in the control group (), there were no statistically significant differences in other baseline characteristics between the two groups. After 48 hours, the NIHSS score was significantly lower in the intervention group (median 8 vs. 6.5, in the control and intervention groups, respectively), but there was no significant difference in the NSE level (). Three months after discharge, the BI was significantly higher in the intervention group (median 8 vs. 9, in the control and intervention groups, respectively). Conclusions. Administration of a single 600000 IU of vitamin D3 could have neuroprotective effects in patients with moderate ischemic stroke, according to its significantly positive effects on functional clinical outcomes (NIHSS and BI), but this effect on the biomarker related to neural damage (NSE) was not significant
Seroprevalence of Pertussis in Adults at Childbearing Age Pre- and Post- COVID-19 in Beijing, China
The number of reported pertussis cases has significantly decreased during the coronavirus disease 2019 (COVID-19) pandemic under the influence of strict public health measures in many countries including China. This study evaluated the prevalence of serum anti-pertussis toxin (anti-PT) IgG antibodies in adults at childbearing age pre- and post- COVID-19 in Beijing, China. Altogether, 2021 serum samples collected from individuals aged 20 to 39 years who attended an annual health examination at the Sixth Medical Center of PLA General Hospital, Beijing, in 2018~2020 were measured by ELISA. The median concentration of anti-PT IgG antibodies among participants in 2020 (2.96 IU/mL) was significantly lower than that in 2018 (3.27 IU/mL) (p = 0.011) and in 2019 (3.24 IU/mL) (p = 0.014). The percentage of participants with anti-PT IgG antibodies higher than 40 IU/mL (indicating a pertussis infection within the past few years) was 1.79% (9/503) in 2018, 2.04% (15/735) in 2019 and 1.66% (13/783) in 2020, respectively. The corresponding numbers of the non-detectable (<5 IU/mL) rate of anti-PT IgG antibodies were 66.60%, 65.99% and 70.24%. Our results showed that there was a significant difference between true and reported incidence rates even during the COVID-19 pandemic. The proportion of adults at childbearing age without pertussis-specific antibodies is high, suggesting that booster vaccinations in adults should be considered in this country
COVID-19 Vaccination Might Induce Reversible Cerebral Vasoconstriction Syndrome Attacks: A Case Report
A 30-year-old male diagnosed three years previously with reversible cerebral vasoconstriction syndrome (RCVS) presented to the department of neurology with an accumulation of attacks mimicking previous RCVS attacks and fulfilling the diagnostic criteria for RCVS after receiving the first Pfizer COVID-19 vaccine. The neurologic exam, blood samples, electrocardiogram (ECG), and computer tomography of the head (CTC) were normal. The patient was treated with the angiotensin 2 receptor antagonist, losartan, with a good response and was discharged with a prescription for losartan lasting until three days after the second Pfizer COVID-19 vaccine. No further RCVS attacks were reported. These findings indicate that the COVID-19 vaccine might induce RCVS attacks in susceptible individuals, and targeting the angiotensin 2 receptor could be a preventive option
Publisher’s Note: Continued Publication of Surgical Techniques Development by MDPI
Surgical Techniques Development was launched in 2011 and has been focused on progressive surgical techniques and advanced technologies, such as laparoscopy, minimally invasive surgery, endoscopy, robotics, and plastic surge