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by Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson
Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via intracerebroventricular (ICV) injections and received 3, 30, or 200 μg rhGNS in 4 doses over 2 weeks or vehicle. Twenty-four hours after the final dose, HS in brain and CSF showed dose-dependent reductions, reaching carrier levels in the higher dose groups. Furthermore, the proteomic perturbations that we described were corrected by rhGNS treatment. Next, Gns KO or carrier adult mice were treated via ICV and received 3, 30 or 200 μg rhGNS or vehicle once every two weeks (Day 1, 15, 29, 43, 57, 71, 85) and were euthanized on day 91. Following treatment, total HS and MPS IIID-specific HS (GlcNAc6S) showed dose-dependent reductions in brain and CSF and markers of neuroinflammation were substantially reduced. ICV enzyme replacement therapy with rhGNS restores CNS pathology of adult MPS IIID mice even with treatment at 14-day intervals, demonstrating preclinical efficacy for MPS IIID.
by Kazuhiko Uchida, Kohji Meno, Tatsumi Korenaga, Shan Liu, Hideaki Suzuki, Yoshitake Baba, Chika Tagata, Yoshiharu Araki, Shuto Tsunemi, Kenta Aso, Shun Inagaki, Sae Nakagawa, Makoto Kobayashi, Tatsuyuki Kakuma, Takashi Asada, Miho Ota, Takanobu Takihara, Tetsuaki Arai
ObjectiveLifestyle habits after middle age significantly impact the maintenance of cognitive function in older adults. Nutritional intake is closely related to lifestyle habits; therefore, nutrition is a pivotal factor in the prevention of dementia in the preclinical stages. Matcha green tea powder (matcha), which contains epigallocatechin gallate, theanine, and caffeine, has beneficial effects on cognitive function and mood. We conducted a randomized, double-blind, placebo-controlled clinical study over 12 months to examine the effect of matcha on cognitive function and sleep quality.
MethodsNinety-nine participants, including 64 with subjective cognitive decline and 35 with mild cognitive impairment were randomized, with 49 receiving 2 g of matcha and 50 receiving a placebo daily. Participants were stratified based on two factors: age at baseline and APOE genotype. Changes in cognitive function and sleep quality were analyzed using a mixed-effects model.
ResultsMatcha consumption led to significant improvements in social acuity score (difference; -1.39, 95% confidence interval; -2.78, 0.002) (P = 0.028) as evaluated by the perception of facial emotions in cognitive function. The primary outcomes, that is, Montreal Cognitive Assessment and Alzheimer’s Disease Cooperative Study Activity of Daily Living scores, showed no significant changes with matcha intervention. Meanwhile, Pittsburgh Sleep Quality Index scores indicated a trend toward improvement with a difference of 0.86 (95% confidence interval; -0.002, 1.71) (P = 0.088) between the groups in changes from baseline to 12 months.
ConclusionsThe present study suggests regular consumption of matcha could improve emotional perception and sleep quality in older adults with mild cognitive decline. Given the widespread availability and cultural acceptance of matcha green tea, incorporating it into the daily routine may offer a simple yet effective strategy for cognitive enhancement and dementia prevention.
To investigate symptom clusters and sentinel symptoms in breast cancer survivors based on self-reported outcomes, explore the impact of sentinel symptoms on patients' quality of life and psychological distress, provide a basis for implementing accurate symptom management.
A cross-sectional survey.
The study was conducted from September 2021 to December 2022. We recruited 281 patients who were re-examined in an outpatient department of a tertiary hospital in Hebei Province. The European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire - Core30 (QLQ-C30), the EORTC Quality-of-Life Questionnaire Breast Cancer - 23 (QLQ-BR23), the Hospital Anxiety and Depression Scale (HADS) were used to conduct the survey. Symptom clusters were explored using principal component analysis, sentinel symptoms were explored using the Apriori algorithm. Correlation analysis was used to explore the relationship between sentinel symptoms and quality of life, correlation with psychological distress. This paper adhered to the STROBE guidelines.
Breast cancer survivors have a wide range of self-reported symptoms in the form of four symptom clusters: a fatigue symptom cluster, a gastrointestinal symptom cluster, a sickness symptom cluster and a surgical trauma-related symptom cluster. Three sentinel symptoms were explored: pain, alopecia and limited function of the upper limbs. Except for sexual function, all of the sentinel symptoms were negatively correlated with patients' quality of life and positively correlated with psychological distress (p < .05).
Breast cancer survivors have a variety of symptoms in the form of four symptom clusters. Pain, alopecia and limited function of the upper limbs are the sentinel symptoms, which affect patients' quality of life and psychological distress.
To summarize existing studies that focused on improving hospitalized patient safety through patient and family engagement interventions to identify priorities and gaps.
A scoping review.
Eight databases and citations of important reviews were searched on 30 September 2022. Two researchers independently screened the records. Then, two researchers extracted the data and cross-checked. The results were synthesized narratively, and a comparison was performed for studies from China and those from other countries.
Ninety-eight studies were included. The results indicated that patient and family engagement interventions were applied to decrease the incidence of patient safety incidents, and to improve the healthcare providers' and patients' knowledge, attitude or practice of patient safety. Most studies only engaged patients and families at the direct care level, and the engagement strategies at the organization and health system levels were insufficient. For stakeholders, many studies failed to consider patients' perspectives in intervention design and report taking staff training as a supportive strategy. Healthcare providers, especially nurses, were the main implementers of current interventions. Certain differences were observed between studies from China and those from other countries in the above aspects.
International interest in engaging patient and family for patient safety is growing. Future studies should enhance the patient and family engagement as a partner in various patient safety at the direct care level, and further explore the engagement at the organization and health system levels.
Nurses, as the main formal caregivers for patients, should promote patient and family engagement in patient safety, especially at direct care level. Nurse should also incorporate the perspectives of patients in the design and implementation of interventions.
PRISMA-ScR Checklist.
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