Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague. The aging signaling pathways were conservative from yeast and worms to mammals. So, we tested if CGA had an effect on aging in Caenorhabditis elegans. We found that CGA could extend the lifespan of C. elegans by up to 20.1%, delay the age-related decline of body movement, and improve stress resistance. We conducted genetic analysis with a series of worm mutants and found that CGA could extend the lifespan of the mutants of eat-2, glp-1, and isp-1, but not of daf-2, pdk-1, akt-1, akt-2, sgk-1, and clk-1. CGA could activate the FOXO transcription factors DAF-16, HSF-1, SKN-1, and HIF-1, but not SIR-2.1. Taken together, CGA might extend the lifespan of C. elegans mainly via DAF-16 in insulin/IGF-1 signaling pathway.
Objective:The purpose of this study was to evaluate the test-retest reliability of gustatory function using whole-mouth taste tests in healthy adults. Methods:Fifty healthy subjects were tested by whole-mouth taste test. The taste test involved 5 tastants（sour, sweet, salty, umami and bitter） and 7 concentrations. The tastant solutions were administered in a pseudo-random order starting with the lowest concentration. Record the perception and recognition scores of each tastant separately. The same operator performed test again by the same method two weeks later. The relative reliability and absolute reliability of the whole-mouth taste test were evaluated with intraclass correlation coefficient（ICC） and standard errors of measurement（SEM）, SEM% respectively. Results:The intraclass correlation coefficient of the perception scores of the sour, sweet, salty, umami and bitter in healthy subjects were from 0.753 to 0.819, ICC values of recognition score range from 0.751 to 0.828. In terms of absolute reliability, the SEM and SEM% values of perception scores were 0.329-0.463 and 6.60%-9.07% respectively; SEM of recognition scores were 0.425-0.581 and SEM%=9.09%-14.66%. Conclusion:The whole-mouth taste test could be a reliable tool for gustatory function test with good test-retest reliability in healthy adults.目的：对全口味觉功能检查法的信度进行评价，分析其在健康成人味觉功能中的一致性及可重复性。 方法：采用全口法对50例健康受试者进行味觉功能检查。味觉功能检查包括酸、甜、咸、鲜、苦五种味剂，每种味剂包含7个浓度梯度，采用伪随机顺序，从最低浓度开始，分别记录每种味剂的感知和识别得分。2周后由同一操作人员以相同方法进行第2次味觉功能检查。全口味觉检查法的相对信度及绝对信度分别使用组内相关系数（ICC）和标准误差（SEM）及SEM%评估。 结果：健康受试者酸、甜、咸、鲜和苦五种味剂感知得分的组内相关系数ICC=0.753~0.819，识别得分的ICC=0.751~0.828。五种味觉感知得分的SEM=0.329~0.463，SEM%=6.60%~9.07%；味觉识别得分的SEM=0.425~0.581，SEM%=9.09%~14.66%。 结论：全口法是一种可靠的主观味觉功能检查方法，在健康成人主观味觉功能评估中有良好的重测信度。.
Background: Intratympanic corticosteroid (IC), intravenous batroxobin (IB) as the treatment for sudden sensorineural hearing loss (SSNHL) has been reported. However, the data on combination therapy (CT) was scarce.Objective: The aim of this retrospective study was to compare the efficacy of IC, IB, and CT in the treatment of SSNHL with diabetes.Material and Methods: A total of 212 SSNHL patients with diabetes, who were initially treated within 14 days of onset of disease, were divided into three groups by treatment modality. The hearing recovery was evaluated by the results of pure-tone test after completion of treatment. The prognostic factors, including age, severity of initial hearing loss, duration to onset of treatment, and audiometric curve type, were further compared.Results: There was a significant difference in hearing recovery by the treatment (p < .05). Recovery rates in the CT group were significantly higher in patients with early treatment than with delayed treatment (p = .021). However, duration and recovery rate was not significantly correlated in IC and IB group (p > .05). In patients recieving early treatment, the recovery rate in CT group was significantly higher than that in IC (p = .013) and IB group (p = .029). Regardless of treatment, the recovery rates were higher in patients with flat and ascending audiograms (p < .05).Conclusions and Significance: Patients receiving combined therapy, especially in the early stage of SSNHL, could achieve significantly superior recovery in the treatment of SSNHL with diabetes, compared with those using IC or IB alone.
Abstract PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T) Tg and Aβ Tg ;α-syn(A53T) Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T) Tg and Aβ Tg ;α-syn(A53T) Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T) Tg and Aβ Tg ;α-syn(A53T) Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans . Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.
Objective:The purpose of this study was to compare the olfactory function examination results of patients with post-viral olfactory dysfunction（PVOD） in different prognostic groups and analyze prognostic factors, especially the influence of olfactory bulb volume（OBV） on prognosis, so as to provide objective basis for clinical diagnosis and treatment. Methods:After approval by the hospital ethics committee, the patients with PVOD admitted to Beijing Anzhen Hospital's outpatient department from January 2019 to December 2019 were followed up for at least 1 year. These patients completed the Sniffin' Sticks test and MRI examination of the olfactory pathway before treatment. According to the results of the Sniffin' Sticks test after 1 year follow-up（threshold-discrimination-identification（TDI） score of the patients was increased at least 6 points）, the patients were divided into two groups as the improvement group and the non-improvement group. The prognostic factors of PVOD patients were preliminarily determined by comparing the differences of various factors and the results of olfactory function examination between the two groups. Results:In this study, 47 patients with PVOD were included, with the smell improvement rate was 53.2%. Compared with the improvement group, the patients in the non-improvement group had longer duration, poorer initial olfactory function, higher olfactory threshold, and poorer olfactory discrimination and recognition ability（All P<0.01）. There was no statistical difference in terms of gender, age, allergic rhinitis and smoking between the two groups（All P>0.05）.The OBV of the non-improvement group was （59.48±23.92） mm³, which was significantly lower than that in the improvement group（[92.77±14.35]mm³, P<0.001）. Multiple logistic regression analysis showed that prognostic factors included course of disease（OR 0.677, 95%CI 0.461-0.993, P=0.046）, initial T value（OR 263.806, 95%CI 1.028-67 675.884, P=0.049） and OBV（OR 1.160, 95%CI 1.002-1.343, P=0.047）. The area under the receiver operating characteristic curve（ROC curve） of OBV was 0.888（0.797-0.979, P<0.001）. The correct diagnostic index of OBV≥78.50 mm³was used to determine the prognosis of olfactory function, with a specificity of 0.818 and a sensitivity of 0.840. The ROC curve analysis showed that the area under the ROC curve of duration was 0.822（0.703-0.940, P<0.001）. The correct diagnostic index of the duration ≤6 months was used to determine the prognosis of olfactory function, with a specificity of 0.727 and a sensitivity of 0.800. The area of T score was 0.793（0.662-0.924, P=0.001）. T score ≥1.25 was used as the correct diagnostic index to determine the prognosis of olfactory function. The specificity and sensitivity were 0.818 and 0.680, respectively. Conclusion:The prognosis of olfactory function in PVOD patients is related to the course of disease, the degree of olfactory loss and OBV. Those with no improvement in olfactory function have a longer disease course, aggravated olfactory damage and reduced OBV than those with improved olfactory function. The factors of Duration ≤6 months, T value ≥1.25 and OBV≥78.50 mm³suggested better prognosis, and the results of objective olfactory examination have greater value in evaluating the prognosis of olfactory function.目的：比较上呼吸道感染后嗅觉障碍（PVOD）患者不同预后组间的嗅觉功能检查结果，分析预后相关因素，尤其嗅球体积（OBV）对预后的影响，为临床诊疗提供客观依据。 方法：对2019年1月—2019年12月于北京安贞医院门诊就诊的PVOD患者进行≥1年的随访，这些患者在治疗前完成Sniffin'Sticks嗅觉测试、嗅通路MRI检查。根据1年随访期后Sniffin'Sticks嗅觉测试结果总分提高≥6分，将患者分为嗅觉功能改善组和嗅觉功能无改善组。比较两组间各因素和嗅觉功能检查结果的差异，初步确定影响PVOD患者的预后因素。 结果：共纳入47例PVOD患者，Sniffin'Sticks嗅觉测试复查结果显示嗅觉改善率为53.2%。与嗅觉功能改善组相比，嗅觉功能无改善组患者病程长，初始嗅觉功能差，嗅觉阈值高，嗅觉辨别和识别能力差（均P<0.01）。两组在性别、年龄、变应性鼻炎和吸烟方面差异均无统计学意义（均P>0.05）。嗅觉功能无改善组的OBV为（59.48±23.92） mm³，明显小于嗅觉功能改善组[（92.77±14.35） mm³]。经多元logistic回归分析预后相关因素包括病程（OR 0.677，95%CI 0.461~0.993，P=0.046），初始T值（OR 263.806，95%CI 1.028~67 675.884，P=0.049）和OBV（OR 1.160，95%CI 1.002~1.343，P=0.047）。ROC曲线分析结果显示，OBV在ROC曲线下面积为0.888（0.797~0.979，P<0.001），以OBV≥78.50 mm³ 正确诊断指数判断嗅觉功能预后良好，其特异性为0.818，敏感性为0.840；病程因素ROC曲线下面积为0.822（0.703~0.940，P<0.001），以病程≤6个月为正确诊断指数判断嗅觉功能预后良好，其特异性为0.727，敏感性为0.800；T值ROC曲线下面积为0.793（0.662~0.924，P=0.001），以T值≥1.25为正确诊断指数判断嗅觉功能预后较好，其特异性为0.818，敏感性为0.680。 结论：PVOD患者嗅觉功能预后与病程、嗅觉损伤程度和OBV有关。嗅觉功能无改善者较嗅觉功能改善者病程延长，嗅觉损伤程度加重和OBV减小。病程≤6个月，T值≥1.25和OBV≥78.50 mm³均提示预后良好，且客观嗅觉检查结果对嗅觉功能预后的评估价值更大。.
Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan.
Objectives/Hypothesis In this study, we assessed gustatory function and whole‐mouth saliva in healthy adults and investigated the association between gustatory function, salivary flow rate (SFR), and dry mouth. Study Design Descriptive clinical study. Methods We recruited 413 participants who reported a normal sense of smell–taste, comprising 206 females and 207 males with an age range of 19 to 80 years. Taste scores were obtained using whole‐mouth tests to evaluate the gustatory function, SFR was assessed using the spitting method, and dry mouth was measured with the visual analog scale. Results The total taste score (TTS) and SFR were significantly negatively correlated with age ( r taste = −0.522, P < .001; r SFR = −0.200, P < .001): TTS was significantly lower after the age of 50 and SFR decreased significantly after age 65. Women exhibited a significantly higher TTS than men ( P < .001). However, there was no effect of sex on SFR. Dry mouth was negatively correlated with TTS ( r = −0.223, P < .01) and SFR ( r = −0.218, P < .01). Multiple regression analysis showed the independent variables of age, sex, and dry mouth predicted 34% of the variation in taste, while the independent variables of age and dry mouth predicted 6.1% of the variation in whole‐mouth saliva. TTS was not significantly correlated with the SFR in healthy adults ( r = 0.094, P = .056). Conclusions Age and dry mouth are important factors affecting gustatory function and whole‐mouth saliva, with women exhibiting better taste sensitivity than men. Furthermore, there is no direct correlation between SFR and gustatory function in healthy adults. Level of Evidence 3 Laryngoscope , 132:844–848, 2022
Abstract Introduction Benign Paroxysmal Positional Vertigo (BPPV) is the most common cause of vertigo in older adults. Due to the high incidence of BPPV in older adults presenting with falls, vestibular assessment, and diagnosis of BPPV and other vestibular disorders has become a recommendation in the World Guidelines for Falls Prevention. There has been a paucity of evidence in well conducted randomised controlled trials (RCTs) to evaluate vitamin D for prevention of BPPV recurrence and its relation to falls and function. Method This is a Phase IIa single centre, placebo controlled, double blind RCT to evaluate vitamin D supplementation together with diet and Canalith Repositioning Procedure [Group A] or diet alone combined with CRP [Gorup B] can reduce recurrence rates of BPPV. Post hoc analyses were performed evaluating BPPV recurrence, falls and function. 53 participants were recruited. 14 were vitamin D replete at baseline [Group C- diet alone], the remaining 39 were randomised into Groups A and B. Group A was associated with 0.75 fewer clinical BPPV recurrences per one person year (IRD -0.75, 95% CI -1.18 to −0.32, P = 0.035). Findings Older adults in the study who suffered a fall during the 12 month follow up had lower Activities of Daily Living scores. They also had poorer Short Physical Performance Battery scores at baseline. Participants in Group A had better 5x sit to stand time compared to Group B even accounting for underlying frailty scores. 25% of participants who fell in the 12 month follow up reported fear of falling compared to 43% in those with no falls in the 12 month follow up. Vitamin D supplementation improved physical performance in 5xchair stand test. Conclusion In this study population, more participants without an incident fall during follow up experience fear of falling, prompting further consideration into the complex concept that is fear of falling.
Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity.
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