Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity

Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test–retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.     

Curing Cats with Feline Infectious Peritonitis with an Oral Multi-Component Drug Containing GS-441524

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn^® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn^®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn^® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn^® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.     

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HR_Q4vsQ1 = 0.95, 95% CI: 0.73–1.23; P_trend = .97; and HR_{per doubling of resistin concentration} = 1.00; 95% CI: 0.84–1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.     

TNF-α and IFN-γ render microglia sensitive to Fas ligand-induced apoptosis by induction of Fas expression and down-regulation of Bcl-2 and Bcl-xL

The immune response in the central nervous system (CNS) involves microglial cells which represent intraparenchymal antigen-presenting cells (APC). To control immune effector mechanisms it may be required to induce apoptosis of APC and thereby limit reactivation of T cells that have invaded the CNS. In the present study we investigated the susceptibility of primary murine microglia and of the murine microglial cell line BV-2 to undergo Fas-mediated apoptosis. Whereas resting microglia are resistant to Fas ligand (FasL) treatment, induction of FasL-mediated apoptosis was achieved by treatment with TNF-α or IFN-γ. The effect of these cytokines was paralleled by up-regulation of Fas expression and down-regulation of Bcl-2 and Bcl-xL but not Bax. Activation of microglia by TNF-α and IFN-γ was also accompanied by increased amounts of mRNA for the apoptosis inhibit FLIP, an effect which did not protect the cells from FasL-induced apoptosis. The FasL-induced cell death pathway in microglia involves reactive oxygen intermediates because the antioxidants N-acetyl-cysteine and glutathione interfere with induction of apoptosis. Surprisingly, microglia constitutively express FasL on the cell surface. However, blocking of endogenous Fas-FasL inter action with Fas-Fc fusion protein did not enhance the survival of microglia, excluding the possibility of suicide or fratricide mechanisms. By their expression of FasL and their TNF-α / IFN-γ-dependent sensitivity to the pro-apoptotic effect of exogenous FasL, microglial cells may influence the course of T cell-mediated diseases of the CNS.     

A review of the reversible MAO-A inhibitor moclobemide in geriatric patients

At present, in Western Europe and the USA 12–15 per cent of the total population are over 65 years old. The portion of mentally abnormal persons in this age group is given at 30 per cent. After dementing disorders, depressive syndromes are the most frequent psychiatric diseases of old age. In the use of antidepressant, psychoactive drugs, one should bear in mind age-related pharmacokinetics and pharmacodynamic changes, frequently present multimorbidity, poor compliance, and drug side effects or interactions as complicating factors. In this report the reversible MAO-A inhibitor, moclobemide, which has now been in clinical use for about 5 years, is examined critically with respect to its pharmacological mode of action, its pharmacokinetic profile, and its tolerability, especially from the psychogeriatric aspect which has received little attention to date. A comparison of the relevant literature shows that moclobemide has advantages over other, classic, antidepressants because of better tolerability, fewer side effects and interactions, shorter latency of effect, and lower toxicity. These advantages, together with a favourable influence on cognitive capacities appear to be very useful, particularly in old age. At this point, however, a conclusive judgment still cannot be reached. Further controlled studies are required for this purpose. © 1998 John Wiley & Sons, Ltd.     

The maximum phonation time as marker for voice treatment efficacy: A network meta-analysis

Purpose

There is a diversity in treatment approaches for voice therapy in which aerodynamic treatment effects between the approaches are lacking. The evidence of voice treatments on the maximum phonation time (MPT) was quantified using the statistical approach of a network meta-analysis (NMA).

Data Sources

Three databases and manual search from inception to November 2021 were evaluated.

Study Selection

Studies were considered which were reports of randomised controlled/clinical trials (RCT) evaluating the efficacy of a specific voice therapy treatment using MPT as an outcome measure in adult participants with voice disorders. Studies were excluded if participants had been diagnosed with neurological-motor-speech disorders or who were vocally healthy. Furthermore, no medical, pharmacological, or technical instrumental treatments were used.

Data Extraction and Synthesis

Preferred Reporting Items for systematic reviews and meta-analyses extension statement guidelines were followed. Two reviewers independently screened citations, extracted data, and assessed risk of bias using PEDro scale. Random effects model was used for meta-analysis.

Results

We identified finally 12 RCT studies (treatment groups n = 285, and control group without an intervention n = 62). Eight interventions were evaluated. The only effective intervention with a significant effect was vocal function exercises (VFE) (mean pre–post difference 6.16 s, 95% confidence interval, 1.18–11.13 s).

Conclusions and Relevance

VFE effectively improved MPT from pre- to post-treatment in comparison with other voice interventions which were identified in the present NMA. Further high-quality intervention studies with large samples sizes, multidimensional measures, and homogeneous groups of dysphonia are needed to support evidence-based practice in laryngology.     

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.