A pilot study examining the relationship between stress and serum cortisol concentrations in women with asthma

The mechanism (s) by which stress exacerbates asthma is unknown. One explanation could be a reduction in endogenous serum cortisol concentrations as a result of stress. Our objective was to determine if a reduction in morning serum cortisol concentrations is associated with higher levels of stress in women with asthma. In this pilot study, seven women with a history of allergic-asthma were prospectively assigned to either low, moderate, or high stress groups based on a combination of their level of current stress and their resources to cope with the stress. After stress group assignment, women donated a morning blood sample, which was analyzed for serum cortisol concentration by an independent laboratory whose personnel were blinded to the subjects' stress status. Three women were assigned to the low stress group, two to the moderate stress group and two to the high stress group. Serum cortisol concentrations ranged from 8 to 23 microg/dl, averaging 14 +/- 6 microg/dl. A Spearman rank correlation indicated that serum cortisol concentrations were significantly inversely related to the stress groupings (r(s) = -0.915; P = 0.025). These results suggest that a reduction in morning serum cortisol concentration may be associated with higher levels of stress and lower resources to cope with the stress in women with allergic-asthma.     

Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas

Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)     

Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may influence disease severity

Genetic diagnosis of steroid-resistant nephrotic syndrome (SRNS) using Sanger sequencing is complicated by the high genetic heterogeneity and phenotypic variability of this disease. We aimed to improve the genetic diagnosis of SRNS by simultaneously sequencing 26 glomerular genes using massive parallel sequencing and to study whether mutations in multiple genes increase disease severity. High-throughput mutation analysis was performed in 50 SRNS and/or focal segmental glomerulosclerosis (FSGS) patients, a validation cohort of 25 patients with known pathogenic mutations, and a discovery cohort of 25 uncharacterized patients with probable genetic etiology. In the validation cohort, we identified the 42 previously known pathogenic mutations across NPHS1, NPHS2, WT1, TRPC6, and INF2 genes. In the discovery cohort, disease-causing mutations in SRNS/FSGS genes were found in nine patients. We detected three patients with mutations in an SRNS/FSGS gene and COL4A3. Two of them were familial cases and presented a more severe phenotype than family members with mutation in only one gene. In conclusion, our results show that massive parallel sequencing is feasible and robust for genetic diagnosis of SRNS/FSGS. Our results indicate that patients carrying mutations in an SRNS/FSGS gene and also in COL4A3 gene have increased disease severity.     

Effect of tegaserod on esophageal pain threshold, regurgitation, and symptom relief in patients with functional heartburn and mechanical sensitivity.

BACKGROUND & AIMS: Tegaserod, a 5-HT4-receptor partial agonist, effectively treats irritable bowel syndrome with constipation. The role of tegaserod in functional disorders of the upper gastrointestinal (GI) tract is unclear. The aims of this study were to determine if tegaserod improves esophageal pain with mechanical and chemical stimuli, GI symptom profile, and global preference in patients with functional heartburn. METHODS: Patients with functional heartburn, as defined by Rome II criteria, underwent esophageal barostat and acid-infusion sensory tests. Mechanical hypersensitivity was required for entry. The baseline GI symptom profile was rated before treatment. Patients were blinded to treatment and randomly assigned to tegaserod 6 mg twice daily or placebo for 14 days, and crossed-over to the alternate treatment after 7 to 10 days of washout. Patients underwent sensory tests and rated GI symptoms after each treatment. Global treatment preference was completed at the end of the study. RESULTS: Forty-two patients (15 men, 27 women; age, 20-68 y) completed the study. The predominant baseline symptoms in addition to heartburn included upper-abdominal pain, upper-abdominal discomfort, regurgitation, chest pain, early satiety, and postmeal bloating. Tegaserod significantly increased balloon pressure to pain (P = .04) and the mean (P = .002) and maximum wall tension at pain (P = .0004). Tegaserod did not alter pain with acid infusion. Tegaserod significantly decreased the frequency of occurrence of heartburn/acid reflux (P = .004), regurgitation (P = .048), and distress from regurgitation (P = .039). The global preference for tegaserod was 63.4% vs 12.2% for placebo. CONCLUSIONS: Tegaserod improved the esophageal pain threshold to mechanical distention, and distressing upper-GI symptoms in patients with functional heartburn.     

The economic burden of maternal mortality on households: evidence from three sub-counties in rural western Kenya

This study explores the consequences of a maternal death to households in rural Western Kenya focusing particularly on the immediate financial and economic impacts. Between September 2011 and March 2013 all households in the study area with a maternal death were surveyed. Data were collected on the demographic characteristics of the deceased woman; household socio-economic status; a history of the pregnancy and health care access and utilization; and disruption to household functioning due to the maternal death. These data were supplemented by in-depth and focus group discussions. The health service utilization costs associated with maternal deaths were significantly higher, due to more frequent service utilization as well as due to the higher cost of each visit suggesting more involved treatments and interventions were sought with these women. The already high costs incurred by cases during pregnancy were further increased during delivery and postpartum mainly a result of higher facility-based fees and expenses. Households who experienced a maternal death spent about one-third of their annual per capita consumption expenditure on healthcare access and use as opposed to at most 12% among households who had a health pregnancy and delivery. Funeral costs were often higher than the healthcare costs and altogether forced households to dis-save, liquidate assets and borrow money. What is more, the surviving members of the households had significant redistribution of labor and responsibilities to make up for the lost contributions of the deceased women. Kenya is in the process of instituting free maternity services in all public facilities. Effectively implemented, this policy can lift a major economic burden experienced by a very large number of household who seek maternal health services which can be catastrophic in complicated cases that result in maternal death. There needs to be further emphasis on insurance schemes that can support households through catastrophic health spending.     

Dementia: Weight Loss and Mealtime Challenges

Weight loss and problems with mealtime are challenges for people with Alzheimer’s disease and related dementias. These challenges are also difficult for caregivers who struggle to ensure that their family members have adequate nutritional intake. Although feeding tubes were once considered an effective solution, there is no evidence that they are effective, they may cause harm, and many authorities suggest that they not be used in people with advanced dementia. This article presents evidence-based recommendations for the assessment and management of weight loss in those with dementia and suggests supportive strategies for families striving to create meaningful mealtimes.