Coconut Oil Supplementation Does Not Affect Blood Pressure Variability and Oxidative Stress: A Placebo-Controlled Clinical Study in Stage-1 Hypertensive Patients

Exploring an alternative to improve the clinical management of hypertension, we tested the hypothesis that food supplementation with coconut oil (EVCO), alone or combined with aerobic exercise training, could exert an antihypertensive effect (primary outcome) in patients with stage 1 hypertension. Forty-five hypertensive volunteers of both genders participated in a placebo-controlled clinical trial. The volunteers were submitted to 24-hour ambulatory blood pressure monitoring, analysis of blood pressure variability (BPV), measurement of serum malondialdehyde (MDA) and nutritional assessment. Results indicate that EVCO consumption had no adverse effects. The supplementation did not increase the caloric intake compared with placebo, and the dietary constituents were similar between groups, except for the saturated fats, especially lauric acid. The analysis of blood pressure indicated absence of antihypertensive effect of EVCO alone or combined with physical training. Furthermore, no effects on blood pressure variability and oxidative stress were observed in the supplemented hypertensive patients. Thus, despite the results observed in pre-clinical studies, the current clinical study did not provide evidence to support the use of coconut oil as an adjuvant in the management of hypertension in humans.     

The expectations and realities of nutrigenomic testing in australia: A qualitative study

BackgroundConsumer genomic testing for nutrition and wellness, (nutritional genomics), is becoming increasingly popular. Concurrently, health‐care practitioners (HPs) working in private practice (including doctors interested in integrative medicine, private genetic counsellors, pharmacists, dieticians, naturopaths and nutritionists) are involved as test facilitators or interpreters.ObjectiveTo explore Australian consumers’ and HPs’ experiences with nutrigenomic testing.MethodSemi‐structured in‐depth interviews were conducted using predominantly purposive sampling. The two data sets were analysed individually, then combined, using a constant comparative, thematic approach.ResultsOverall, 45 interviews were conducted with consumers (n = 18) and HPs (n = 27). Many of the consumer interviewees experienced chronic ill‐health. Nutrigenomic testing was perceived as empowering and a source of hope for answers. While most made changes to their diet/supplements post‐test, self‐reported health improvements were small. A positive relationship with their HP appeared to minimize disappointment. HPs’ adoption and views of nutrigenomic testing varied. Those enthusiastic about testing saw the possibilities it could offer. However, many felt nutrigenomic testing was not the only ‘tool’ to utilize when offering health care.DiscussionThis research highlights the important role HPs play in consumers’ experiences of nutrigenomics. The varied practice suggests relevant HPs require upskilling in this area to at least support their patients/clients, even if nutrigenomic testing is not part of their practice.Patient or public contributionAdvisory group included patient/public group representatives who informed study design; focus group participants gave feedback on the survey from which consumer interviewees were sourced. This informed the HP data set design. Interviewees from HP data set assisted with snowball sampling.     

The role of response domain and scale label in the quantitative interpretation of patient-reported outcome measure response options

Quality of Life Research - Uncertainties exist in how respondents interpret response options in patient-reported outcome measures (PROMs), particularly across different domains and for different...     

Vaccine-induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T_1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T_1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.     

Injection of endothelin-1 into the raphe obscurus of rats induces depressor responses predominantly through endothelin ETA receptors

We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the nucleus raphe obscurus of rats. These studies showed dense binding of [¹²⁵I]PD151242 (for endothelin ET_A receptors), while tissues incubated with [¹²⁵I]BQ3020 (for endothelin ET_B receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonists FR 139317 (endothelin ET_A receptor-selective antagonist), SB 209670 (endothelin ET_A/ET_B receptor-non-selective antagonist) and BQ-788 (endothelin ET_B receptor-selective antagonist) on the blood pressure responses following administration of endothelin-1 into the nucleus raphe obscurus. The basal mean arterial blood pressure (MABP) of the rats was 110 ± 7 mmHg (n = 5). This was decreased in a dose-dependent manner by endothelin-1 (0.1, 1 and 10 pmol) microinjected into the nucleus raphe obscurus. This effect occurred within 1–6 s and recovered within 4 ± 1.2 min at a dose of 10 pmol. The doses of 0.1 pmol and 1 pmol ET-1 had responses which lasted 1 ± 0.4 min and 2 ± 0.2 min, respectively. Small decreases in heart rate accompanied the MAP responses to endothelin-1. For instance, the heart rate decreased by 16 ± 4 beats min^–1 after 10 pmol endothelin-1 (control, 366 ± 6 beats min^–1, n = 5). Decreases in blood pressure induced by endothelin-1 were greatly reduced by pre-administration to the nucleus raphe obscurus of FR139317 (5 nmol/rat) or SB209670 (3 nmol/rat; 97 ± 7% and 95 ± 6%, P < 0.01, n = 5, respectively), but were not affected by BQ-788 (50 nmol/rat; 8 ± 3%, P > 0.05, n = 5). The antagonists did not influence heart rate when injected to the nucleus raphe obscurus prior to endothelin-1. FR139317 (0.5 nmol) and SB209670 (0.3 nmol) had no effects on endothelin-induced changes in arterial blood pressure. Therefore, the autoradiographic study showed that there are binding sites for ET-1 within the nucleus raphe obscurus of rats, which are predominantly of ET_A type. The in vivo study showed that ET_A receptors are the predominant mediators of depressor responses induced by endothelin-1 injected into this nucleus. Received: 6 August 1998 / Accepted: 16 February 1999     

Association of gestational diabetes with abnormal maternal vascular endothelial function

Objective To evaluate vascular endothelial function in isolated small arteries from women with gestational diabetes.
Methods Small subcutaneous arteries (mean luminal diameter ∼ 250μm) were dissected from biopsies obtained at caesarean section in 14 normotensive women with gestational diabetes and in 18 normotensive nondiabetic pregnant women. Vascular function was determined after mounting the arteries on a small vessel myograph.
Results Pre-constricted arteries from gestational diabetic pregnant women demonstrated poor relaxation to acetylcholine, an endothelium-dependent vasodilator (pEC₅₀, mean [SE], 6.98 [0.10] vs normal pregnant, 7.28 [0.08],   P < 0.03  ; % maximum relaxation, median [range], 88.2 [42.4–994] vs normal pregnant 94.2 [71.8–100.0],   P < 0.01  ). In the presence of indomethacin relaxation to acetylcholine was similar in both groups suggesting a deficiency in dilator prostaglandin synthesis in the arteries from the diabetic women. The nitric oxide synthase inhibitor N -monomethyl-L-arginine further reduced sensitivity of arteries to acetylcholine but to a similar degree in both normal pregnant and gestational diabetic women. Relaxation to sodium nitroprusside, an indicator of sensitivity of the vascular smooth muscle to nitric oxide, was similar in both groups.
Conclusions Maternal vascular endothelial dysfunction may contribute to the increased incidence of cardiovascular disorders in women with gestational diabetes.     

Economic evaluation of pertussis prevention by whole-cell and acellular vaccine in Germany

Acellular pertussis vaccines are less reactogenic than whole cell pertussis vaccines, but they are also more expensive. Based on simulation models, we compared the costs and effects of three alternative pertussis vaccination strategies in German children to ”no prevention”: (1) vaccination with whole-cell vaccine at 45% coverage (vaccine efficacy 90%), (2) vaccination with acellular vaccine at 45% coverage (vaccine efficacy 85%), and (3) vaccination with acellular vaccine at 90% coverage. In the two low coverage scenarios expected annual savings in direct medical costs through prevention of disease were larger for whole-cell than for acellular vaccination (252 vs 216 million DM, respectively). Direct costs for treating the more important adverse events induced by whole-cell vaccination (16.9 million DM annually) did not outweigh the higher direct costs of pertussis infections not prevented with the acellular vaccine and the higher price of the acellular vaccine. However, vaccination with acellular pertussis vaccine rapidly becomes as cost saving as vaccination with whole-cell vaccine as soon as vaccination coverage can be raised from 45% to 52.5% with acellular vaccine. Acellular vaccination is also the superior alternative when considering indirect cost savings resulting from reduction in work-loss due to adverse events. Conclusion In our simulations, the most cost-effective pertussis prevention strategy was the use of an effective whole-cell vaccine with a high coverage rate. Introduction of the more expensive acellular pertussis vaccines becomes cost saving if at least a 7.5% increase in coverage is achieved. If also non-medical indirect costs to parents resulting from vaccine associated side-effects are accounted for, acellular vaccines may be more cost-effective also in countries with already high whole-cell vaccine coverage. Received: 22 April 1997 / Accepted in revised form: 21 November 1997     

Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred.

PURPOSE: Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs. PATIENTS AND METHODS: Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. RESULTS: In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs. CONCLUSION: These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.