Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria.

Chronic cerebral hypoperfusion (CCH) is an enduring inadequate blood flow to the brain, resulting in vascular dementia (VaD). However, the effective treatment strategies are lacking. Supplementing with nicotinamide adenine dinucleotide (NAD+) has shown neuroprotective benefits in other neurodegenerative disorders. Nicotinamide riboside (NR), as a precursor of NAD+, is believed to hold promise in improving mitochondrial health, autophagy, and cognitive function. Meanwhile, NR has unique oral bioavailability, good tolerability, and minimal side effects, and it is the most promising for clinical translation. However, the effectiveness of NR in treating CCH-related VaD is still uncertain. The present study examined the neuroprotective effects of NR supplementation and its underlying mechanisms in a CCH rat model. The rats with CCH were given NR at a daily dosage of 400 mg/kg for 3 months. NR supplementation increased blood and brain NAD+ levels and improved brain function in CCH rats, including cognitive function and oxygenation capacity. It also reduced hippocampal neuronal loss and abnormalities and mitigated the decrease in dendritic spine density. The analysis of RNA sequencing in hippocampal tissue supports these findings. Electron microscopy and protein detection results suggest that NR may maintain mitochondrial structural integrity and exert a protective role by attenuating mitochondrial fission and impaired autophagy flux caused by CCH. In conclusion, these findings offer evidence for the neuroprotective potential of NR supplementation in ameliorating cognitive impairment induced by CCH.

SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response

The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8+ T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8+ T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8+ T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8+ T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8+ T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8+ T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238. Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8+ T cell responses elicited by infection of mutated strains or vaccination. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/437363v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@b9f2cdorg.highwire.dtl.DTLVardef@1f39e3dorg.highwire.dtl.DTLVardef@119c313org.highwire.dtl.DTLVardef@565388_HPS_FORMAT_FIGEXP M_FIG C_FIG

CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation 5L>F significantly decreased the proportion of specific T cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.

Efficacy of treadmill training on neuropsychiatric symptoms and quality of life among elderly Alzheimer's disease / 中国实用护理杂志

Objective@#To analyze effect of Treadmill Training on neuropsychiatric symptoms and quality of life in elderly patients with Alzheimer′s disease.@*Methods@#From May 2018 to November 2018, the experimental design was adopted. The patients with 55-75 years old AD, the First Affiliated Hospital of Quanzhou Fujian Medical University were randomly divided into groups. Group (treadmill training, 68 patients), control group (no intervention, 68 patients). The two groups were evaluated before the training and 20 weeks after training, using the Neuropsychology Scale (NPI-Q) and the Alzheimer's disease Quality of Life Questionnaire (QOL-AD), and the t-test, two-factor repeated measures analysis of variance, etc. Statistical methods for data analysis.@*Results@#There were no significant differences in neuropsychiatric scores and QOL scores between the two groups before training (P>0.05). After training through a 20-week treadmill, the total score of neuropsychiatric symptoms in patients with Alzheimer's disease in the experimental group (t=-1.317, P=0.204 before training; t=-10.01, P=0.046 after 20 weeks of training), affective symptoms (Before training, t=-1.684, P=0.092; t=-11.26, P=0.043 after 20 weeks of training, psychiatric symptoms (t=1.168 before training, P=0.235; t=-9.94 after training for 20 weeks, P=0.034)), behavioral symptoms (t=1.952 before training, P=0.129; t=-3.61, P=0.028 after 20 weeks of training), and QOL total score (t=1.452, P=0.140 before training; t=22.27 after training, P=0.040) were statistically different; and the improvement of neuropsychiatric symptoms in the experimental group was significantly different from that in the control group (F=23.10, P=0.000), while the QOL of the experimental group was also significantly different from the control group (t=- 8.88, P=0.000).@*Conclusion@#Non-pharmacological treatment with treadmill training can improve neuropsychiatric symptoms and improve quality of life in elderly AD patients.

Effects of low resistance training using elastic band on lower extremity functional and health-related quality of life in elderly with degenerative knee arthritis / 中国实用护理杂志

Objective@#Understand the effects of low-resistance elastic band exercise on lower limb function and health-related quality of life in elderly with degenerative knee arthritis.@*Methods@#The 79 patients with degenerative knee arthritis were randomly divided into observation group (40 cases) and control group (39 cases). In the observation group, low-resistance elastic bands were exercised for 12 weeks and 2 times per week. In the control group, routine care measures. The following limb function assessment scales and health-related quality of life scales were evaluation tools, and statistical analysis was performed based on the measured data.@*Results@#There was no significant difference in the score of gait balance, isotonic contraction, knee muscle strength of lower extremity function before intervention between the two groups (P>0.05) . The score of gait balance, isotonic contraction, knee muscle strength of lower extremity function after intervention was (4.63±0.07) , (4.57±0.08) , (4.53±0.44) points in the observation group, and (3.60±0.23) , (3.59±0.12) , (3.86±0.09) points in the control group, and there was significant difference between the two groups(t=1.982, 1.968, 2.356, all P<0.05). There was no significant difference in the score of joint activities, body function, social interaction, emotional state, mental health of quality of life before intervention between the two groups (P>0.05) . The score of joint activities, body function, social interaction, emotional state, mental health of quality of life after intervention was (4.48±0.12) , (4.57±0.22) , (4.38±0.57) , (4.29±0.29) , (4.33±0.41) points in the observation group, and (3.46±0.52) , (3.48±0.25) , (3.59±0.97) , (3.45±0.83) , (3.51±0.52) points in the control group, and there was significant difference between the two groups (t=2.405-3.564, all P<0.01) .@*Conclusions@#For elderly, low-resistance elastic band exercise is easy to learn in operation, safety and practicality are also higher, as a reference to improve the lower limb function and health-related quality of life in elderly patients with degenerative knee.

Efficacy of treadmill training on neuropsychiatric symptoms and quality of life among elderly Alzheimer's disease / 中国实用护理杂志

Objective To analyze effect of Treadmill Training on neuropsychiatric symptoms and quality of life in elderly patients with Alzheimer′s disease. Methods From May 2018 to November 2018, the experimental design was adopted. The patients with 55-75 years old AD, the First Affiliated Hospital of Quanzhou Fujian Medical University were randomly divided into groups. Group (treadmill training, 68 patients), control group (no intervention, 68 patients). The two groups were evaluated before the training and 20 weeks after training, using the Neuropsychology Scale (NPI-Q) and the Alzheimer's disease Quality of Life Questionnaire (QOL-AD), and the t-test, two-factor repeated measures analysis of variance, etc. Statistical methods for data analysis. Results There were no significant differences in neuropsychiatric scores and QOL scores between the two groups before training (P＞0.05). After training through a 20-week treadmill, the total score of neuropsychiatric symptoms in patients with Alzheimer's disease in the experimental group (t=-1.317, P=0.204 before training; t=-10.01, P=0.046 after 20 weeks of training), affective symptoms ( Before training, t=-1.684, P=0.092; t=-11.26, P=0.043 after 20 weeks of training, psychiatric symptoms (t=1.168 before training, P=0.235; t=-9.94 after training for 20 weeks, P=0.034) ), behavioral symptoms (t=1.952 before training, P=0.129; t=-3.61, P=0.028 after 20 weeks of training), and QOL total score (t=1.452, P=0.140 before training; t=22.27 after training, P=0.040) were statistically different; and the improvement of neuropsychiatric symptoms in the experimental group was significantly different from that in the control group (F=23.10, P=0.000), while the QOL of the experimental group was also significantly different from the control group (t=- 8.88, P=0.000). Conclusion Non-pharmacological treatment with treadmill training can improve neuropsychiatric symptoms and improve quality of life in elderly AD patients.

Effects of low resistance training using elastic band on lower extremity functional and health-related quality of life in elderly with degenerative knee arthritis / 中国实用护理杂志

Objective Understand the effects of low-resistance elastic band exercise on lower limb function and health-related quality of life in elderly with degenerative knee arthritis. Methods The 79 patients with degenerative knee arthritis were randomly divided into observation group (40 cases) and control group (39 cases). In the observation group, low-resistance elastic bands were exercised for 12 weeks and 2 times per week. In the control group, routine care measures. The following limb function assessment scales and health-related quality of life scales were evaluation tools, and statistical analysis was performed based on the measured data. Results There was no significant difference in the score of gait balance, isotonic contraction, knee muscle strength of lower extremity function before intervention between the two groups(P>0.05). The score of gait balance, isotonic contraction, knee muscle strength of lower extremity function after intervention was(4.63 ± 0.07),(4.57 ± 0.08),(4.53 ± 0.44)points in the observation group, and(3.60±0.23),(3.59±0.12),(3.86±0.09)points in the control group, and there was significant difference between the two groups(t=1.982, 1.968, 2.356, all P<0.05). There was no significant difference in the score of joint activities, body function, social interaction, emotional state, mental health of quality of life before intervention between the two groups(P>0.05). The score of joint activities, body function, social interaction, emotional state, mental health of quality of life after intervention was(4.48± 0.12),(4.57±0.22),(4.38±0.57),(4.29±0.29),(4.33±0.41)points in the observation group, and(3.46± 0.52),(3.48±0.25),(3.59±0.97),(3.45±0.83),(3.51±0.52)points in the control group, and there was significant difference between the two groups(t=2.405-3.564, all P<0.01). Conclusions For elderly, low-resistance elastic band exercise is easy to learn in operation, safety and practicality are also higher, as a reference to improve the lower limb function and health-related quality of life in elderly patients with degenerative knee.

The development and assessment of Knee Osteoarthritis Self-Care Questionnaire for Elderly / 中国实用护理杂志

Objective To develop Knee Osteoarthritis Self-Care Questionnaire for Elderly (KOSCQE), and test reliability and validity of the scale. Methods Based on self care theory, with reference to International Knee Documentation Committee Subjective Knee Form, combined with literature analysis and through semi-structured interviews, the item pool of the scale was established. A total of 148 elderly were investigated by questionnaire survey. Results KOSCQE extracted 5 common factors with 26 items, and the total variance contribution rate was 68.972%;the item load factor was 0.576 to 1.872, item level content validity index was 0.901-0.928, factor in overall content validity index of 0.916;total Cronbach αcoefficient was 0.898, test-retest reliability was 0.864, and the confirmatory factor analysis showed that:χ2/df=1.09, goodness of fit index =0.942, root mean square error of approximation=0.020, adjusted goodness of fit index=0.964, normed fit index=0.960, comparative fit index=0.948, relative fit index=0.931, incremental fit index=0.918, parsimony goodness of fit index=0.891. Conclusions The reliability and validity of the KOSCQE of the elderly accord with the requirements of the measurement of the scale, it can improve the elderly's awareness of self care and quality of life of the knee osteoarthritis.