Pathogenic Potential of Eomesodermin-Expressing T-Helper Cells in Neurodegenerative Diseases

Eomesodermin-expressing (Eomes⁺) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes⁺ Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes⁺ Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes⁺ Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes⁺ Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093–1098     

Staff knowledge,attitudes and practices regarding glycaemic management in adult intensive care units: A national survey

Background

Hyperglycaemia is common in critically ill adult patients. Many studies have identified the content, methods, and effects of glycaemic control but have not explored the effects of knowledge, attitudes, and practices (KAP) on glycaemic control in critically ill adults. Various factors also influence the KAP of intensive care unit (ICU) staff.

Aims

To assess KAP regarding glucose management for critically ill adults among nurses and medical professionals and identify the factors that influence their KAP in ICUs.

Methods

A multicentre cross-sectional survey.

Results

In total, 403/459 (response rate: 87.8%) participants from ICUs in nine tertiary hospitals in China participated in this study, 82.4% of whom were female and 93.4% of whom were nurses. The mean work experience was 8.88 years, and the mean critical care experience was 6.59 years. The scoring rate for the three dimensions of knowledge, attitudes, and practices were 82.35%, 87.69%, and 76%, respectively. We did not find any other factors affecting the KAP scores except for the level of knowledge awareness (p < 0.001), awareness of the importance (p < 0.001), and training for glucose control (p = 0.004).

Conclusion

ICU staff KAP regarding glycaemic control in critically ill adults among ICU professionals were acceptable in China. However, ICU professionals' current knowledge regarding nutrition, glucose variability, and skills related to glucose management could be improved.

Relevance to Clinical Practice

ICU educators should provide more skills-related training for healthcare professionals in the glycaemic management of critically ill adults. Moreover, the process of managing blood glucose in adult ICU patients is a collaborative, multidisciplinary team effort, with monitoring and feedback required during implementation.     

Whites and African-Americans in headache specialty clinics respond equally well to treatment

This study sought to determine if Whites and African-Americans respond similarly to headache treatment administered in 'real-world' headache specialty treatment clinics. Using a naturalistic, longitudinal design, 284 patients receiving treatment for headache disorders completed 30-day daily diaries that assessed headache frequency and severity at pretreatment and 6-month follow-up and also provided data on their headache disability and quality of life at pretreatment and 1-, 2- and 6-month follow-up. Controlling for socioeconomic status and psychiatric comorbidity, hierarchical linear models found that African-Americans and Whites reported significant reductions in headache frequency and disability and improvements in life quality over the 6-month treatment period. African-Americans, unlike Whites, also reported significant decreases in headache severity. Nevertheless, Africans-Americans had significantly more frequent and disabling headaches and lower quality of life after treatment relative to Whites. Although Whites and African Americans responded favourably to headache treatments, more efficacious treatments are needed given the elevated level of headache frequency that remained in both racial groups following treatment.     

A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents

Chronic infection with the protozoan parasite Trypanosoma cruzi is a major cause of morbidity and mortality in Latin America. Drug treatments for the associated illness, Chagas disease, are toxic and frequently unsuccessful. In a screening effort against the drug target protein farnesyltransferase, we identified a series of disubstituted imidazoles with highly potent anti-T. cruzi activity that apparently acted through a mechanism independent of protein farnesylation. Metabolic labeling studies of T. cruzi suggested that sterol biosynthesis was inhibited. Combined GC/MS analysis confirmed depletion of cellular sterols and suggested that the site of action was sterol 14-demethylase, a cytochrome P450 enzyme. Spectral studies with recombinant T. cruzi sterol 14-demethylase demonstrated that the compounds bind directly to this enzyme. Two of the compounds were well absorbed when given orally to mice, gave sustained plasma levels, and were well tolerated. The compounds were administered orally to mice with acute T. cruzi infection and caused dramatic decrease in parasitemia and led to 100% survival. These disubstituted imidazole compounds can be prepared by a relatively short synthetic route and represent a structural class with potent anti-T. cruzi activity.