BACKGROUND: Our previous observational cohort study, the Kashima Scan Study (KSS), identified associations between lifestyle, cerebral small vessel disease (SVD) as detected by magnetic resonance imaging of the brain, and disease outcomes including cognitive impairment and vascular diseases. However, established modifiers of the outcomes such as genetic background, drinking and exercise habits, and socioeconomic status were not considered. Regarding genetic factors in particular, the ALDH2 rs671 variant, East Asian-specific diversity, and APOE status are expected to have strong effects. The aim of KSS-2 is to examine the interactions of genetic background, lifestyle factors including drinking habit, socioeconomic status, and/or SVD markers for cognitive impairment, vascular disease, and death. METHOD: The KSS-2 is a prospective regional observational study of a healthy Japanese cohort that will clarify lifestyle habits to better maintain brain health from midlife by genotype. Japanese adults who underwent brain health checkups at their own expense are enrolled and will be followed-up for 10 years. We will extend the protocol of the KSS to include genetic background and potential confounding factors, including lifestyle (including drinking and exercise habit) and socioeconomic status, and perform survival analyses. The study outcomes are cognitive impairment, vascular events, and death. RESULTS: We enrolled 908 healthy adults (mean age 64.2 years; range 35 to 84 years; 41% male) from September 1, 2018 until December 31, 2024. CONCLUSION This study will provide important insights into the development of individualized health intervention strategies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cerebral Small Vessel Diseases/diagnostic imaging* ; Japan/epidemiology* ; Life Style ; Magnetic Resonance Imaging ; Prospective Studies ; Observational Studies as Topic

The following report illustrates a rare case of dysphagia caused by secondary adrenal insufficiency in a patient with isolated ACTH deficiency. A 76-year-old man with progressive appetite loss, weight loss and general fatigue was hospitalized due to dehydration, aspiration pneumonia and hypoglycemia. He was unable to stand and walk by himself. His serum cortisol and ACTH levels were both low. An endocrinological examination resulted in a diagnosis of isolated ACTH deficiency. Following the administration of 15mg of glucocorticoids daily, his symptoms diminished without dysphagia. Furthermore, we investigated his swallowing function using a videofluoroscopic examination of swallowing (VF). The VF showed an impaired laryngeal movement as well as an upper esophageal opening and severe aspiration without a delay in his swallowing reflex. Oral intake was judged to be impossible, but his swallowing function gradually improved and he was able to resume eating all of his meals 2 months after treatment. Dysphagia is not a common symptom in ACTH deficient patients but a few similar cases have been reported. The swallowing function of the patients in these cases was not evaluated in detail, so we evaluated this case according to the results of the VF and the patient's process of recovery. Careful monitoring of swallowing function and appropriate treatment for both dysphagia and adrenocortical failure are required for the recovery of such patients. In conclusion, practitioners should be wary of isolated ACTH deficiency in elderly patients with progressive weight loss and dysphagia.

An in vitro infection system of Trypanosoma cruzi and HeLa cells was used to measure the anti-T. cruzi activities of various calcium antagonists classified into dihydropyridines, diphenylalkylamines, and benzothiazepines and of allopurinol and benznidazole as medium and highly effective reference compounds, respectively. Six dihydropyridines (10 μM each), i. e. nifedipine, nicardipine, nimodipine, nisoldipine, nitrendipine, and amlodipine, decreased the rates of infection of HeLa cells from 11.7% (control) to 5.8, 0.9, 1.2, 3.6, 5.9, and 1.7%, respectively. Nicardipine and amlodipine were highly toxic to HeLa cells, causing detachment of cells from coverslips. Nimodipine was thus the most effective inhibitor tested against T. cruzi infection in HeLa cells. Verapamil and gallopamil (diphenylalkylamines), diltiazem and midazolam (benzothiazepines), and allopurinol (positive control) were less effective than nimodipine. IC₅₀ values, the concentrations of compounds that elicited a 50% reduction in the infection rates of HeLa cells, were 2.5, 2.6, 1.3, 2.1, and 1.7 μM for nicardipine, nimodipine, amlodipine, verapamil, and benznidazole, respectively, while the values for nifedipine, diltiazem, and allopurinol were much higher. Nicardipine, amlodipine, and verapamil again showed significant cytotoxicities to HeLa cells. When Swiss 3T3 fibroblasts replaced HeLa cells, nimodipine markedly lowered the host-cell-infection rate, with an IC₅₀ value of 8.3 nM. Thus, nimodipine is expected to be a highly effective anti-T. cruzi lead compound, with low cytotoxicity to mammalian cells. Structural formulas of nimodipine and nicardipine in relation to their low and high cytotoxicities, respectively, against HeLa cells are discussed.