Factors Affecting Catecholamines in Caregivers of Patients with Dementia

Background: Caregivers of dementia patients have significantly higher levels of serum IL-6 and CRP compared to non-caregivers, and the accumulation of everyday stressors reportedly promotes the induction of inflammatory markers. However, few studies have identified factors that affect catecholamine levels in caregivers who experience a combination of physical and mental stress from caregiving. Purpose: This study aimed to identify physical factors that impact catecholamine levels in caregivers of dementia patients. Methods: Participants were elderly caregivers living together with elderly Alzheimer’s-type dementia patients. We performed logistic regression analysis, with levels of adrenaline, noradrenaline, and dopamine (indicators of catecholamine) as dependent variables. Results: Caregiver BMI had a significant impact on adrenaline levels (OR: 0.792; 95%CI: 0.654-0.960) and noradrenaline levels (OR: 1.210; 95%CI: 1.009-1.451), whereas age had a significant impact on dopamine levels (OR: 1.162; 95%CI: 1.019- 1.324). Discussion: While caregiver BMI significantly impacted adrenaline and noradrenaline levels, the mechanism underlying these relationships is unclear. One possibility is that obesity (BMI) and a rise in sympathetic nerve activity contributed to hypertension. Our findings suggest that chronic stress in elderly caregivers may potentially impair the dopaminergic activation system in the brain. Conclusion: There is a need to identify factors which increase BMI in caregivers. Future studies aimed at gaining a better understanding of the lifestyle habits of caregivers and intervention studies aimed at reducing their BMI are warrante

Real-time TIRF observation of vinculin recruitment to stretched α-catenin by AFM

Adherens junctions (AJs) adaptively change their intensities in response to intercellular tension; therefore, they integrate tension generated by individual cells to drive multicellular dynamics, such as morphogenetic change in embryos. Under intercellular tension, α-catenin, which is a component protein of AJs, acts as a mechano-chemical transducer to recruit vinculin to promote actin remodeling. Although in vivo and in vitro studies have suggested that α-catenin-mediated mechanotransduction is a dynamic molecular process, which involves a conformational change of α-catenin under tension to expose a cryptic vinculin binding site, there are no suitable experimental methods to directly explore the process. Therefore, in this study, we developed a novel system by combining atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF). In this system, α-catenin molecules (residues 276–634; the mechano-sensitive M1-M3 domain), modified on coverslips, were stretched by AFM and their recruitment of Alexa-labeled full-length vinculin molecules, dissolved in solution, were observed simultaneously, in real time, using TIRF. We applied a physiologically possible range of tensions and extensions to α-catenin and directly observed its vinculin recruitment. Our new system could be used in the fields of mechanobiology and biophysics to explore functions of proteins under tension by coupling biomechanical and biochemical information

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.</p

Mechano-adaptive sensory mechanism of α-catenin under tension

The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, α-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, α-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how α-catenin retains its activated state while avoiding unfolding under tension. Using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated α-catenin fragment had higher mechanical stability than a non-activated fragment. The results of our experiments using mutated and segmented fragments showed that the key intramolecular interactions acted as a conformational switch. We also found that the conformation of α-catenin was reinforced by vinculin binding. We demonstrate that α-catenin adaptively changes its conformation under tension to a stable intermediate state, binds to vinculin, and finally settles into a more stable state reinforced by vinculin binding. Our data suggest that the plastic characteristics of α-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels

Oral hypofunction in the older population : Position paper of the Japanese Society of Gerodontology in 2016

Background: There is growing international interest in identifying the effects of ageing on oral health and on appropriate strategies for managing oral disorders. The Japanese Society of Gerodontology (JSG), as the official representative of researchers and clinicians interested in geriatric dentistry in Japan, makes several recommendations on the concept of “oral hypofunction.” Aims: This study proposes diagnostic criteria and management strategies to reduce the risk of oral hypofunction among older people. Conceptual Framework: We define oral hypofunction as a presentation of 7 oral signs or symptoms: oral uncleanness; oral dryness; decline in occlusal force; decline in motor function of tongue and lips; decline in tongue pressure; decline in chewing function; and decline in swallowing function. The criteria of each symptom were determined based on the data of previous studies, and oral hypofunction was diagnosed if the criteria for 3 or more signs or symptoms were met. Conclusions: We recommend that more evidence should be gathered from clinical studies and trials to clarify our diagnostic criteria and management strategies

Her yol Roma'ya varmaz!

Taha Toros Arşivi, Dosya Adı: Taha Torosİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140