The effect of a multicomponent intervention to promote community activity on cognitive function in older adults with mild cognitive impairment: A randomized controlled trial

ObjectivesThis study aimed to examine the effectiveness of a multicomponent intervention combining physical, cognitive, and social activities developed to promote community activity in improving cognitive function in older adults with mild cognitive impairment (MCI).DesignSingle-blind randomized controlled trial.SettingA total of 83 Japanese older adults with MCI participated in the study from April to September 2017.InterventionsParticipants were randomly assigned to either the multicomponent intervention group (n = 41), attending 90-minute physical, cognitive, or social activity sessions using community resources twice weekly, or the health education control group (n = 42).OutcomesThe primary outcomes were cognitive functions, and the secondary outcomes were grip strength, walking speed, depressive symptoms, physical activities, number of outdoor activities, and conversation time.ResultsAnalysis using linear mixed models revealed significantly greater improvements in the intervention group in spatial working memory (p = 0.024) following intervention compared with the control group. Time spent in moderate-to-vigorous physical activity (p = 0.048) and step count (p = 0.059) decreased from the baseline post-intervention in the control group, whereas the baseline was maintained in the intervention group. No significant between-group differences were found post-intervention in the other primary and secondary outcomes.ConclusionsThis study showed that a 24-week multicomponent intervention program was effective in improving spatial working memory and maintaining physical activity in older adults with MCI. A follow-up investigation is required to determine whether continuation of physical, cognitive, and social activity can prevent dementia or reverse MCI in older adults.     

Synthesis, anti-HIV and antitubercular activities of nelfinavir diester derivatives.

Nelfinavir diesters were prepared by reacting nelfinavir with two molar amount of an appropriate substituted aromatic/aliphatic acid in the presence of dicylohexyl carbodiimide as the carboxyl group activator and 4-dimethylamino pyridine as catalyst. The synthesized compounds were evaluated for their inhibitory effects on the replication of HIV-1 (IIIB) in MT-4 cells by MTT assay method and antimycobacterial activity against Mycobacterium tuberculosis H37Rv by agar dilution method. Compound 3f emerged as the most potent anti-HIV agent with EC(50) of 0.043 microM and CC(50) more than >10 microM and was more potent than parent nelfinavir (EC(50) of 0.060 microM) and also showed antimycobacterial activity (MIC 8.49 microM).     

Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation

To what extent does the visual system's activity fluctuate when no sensory stimulation is present? Here, we studied this issue by examining spontaneous fluctuations in BOLD signal in the human visual system, while subjects were placed in complete darkness. Our results reveal widespread slow fluctuations during such rest periods. In contrast to stimulus-driven activity, during darkness, functionally distinct object areas were fluctuating in unison. These fMRI fluctuations became rapidly spatially de-correlated (39% drop in correlation level, P < 0.008) during visual stimulation. Functional connectivity analysis revealed that the slow spontaneous fluctuations during rest had consistent and specific neuro-anatomical distribution which argued against purely hemodynamic noise sources. Control experiments ruled out eye closure, low luminance and mental imagery as the underlying sources of the spontaneous fluctuations. These results demonstrate that, when no stimulus is present, sensory systems manifest a robust level of slow organized fluctuation patterns.     

Sympatho-vagal interaction in the recovery phase of exercise

Reciprocal autonomic regulation occurs during incremental exercise. We hypothesized that sympatho-vagal interplay may become altered after exercise because of the differences in recovery patterns of autonomic arms. The cardiac vagal activity was assessed by measurement of beat-to-beat R-R interval oscillations using a Poincaré plot method (SD1), and muscle sympathetic nervous activity (MSNA) was measured from peroneus nerve by a microneurography technique during and after exercise in 16 healthy subjects. Autonomic regulation was compared between the rest and after exercise (3·5 ± 1·0 min after exercise) at equal heart rates (HR). SD1 was at the equal level at the recovery phase (40 ± 21 ms) compared to the resting condition (38 ± 16 ms, P = ns) at comparable HR (57 ± 10 for both). MSNA was higher at the recovery phase (40 ± 19 burst per 100 heartbeats) than at rest (25 ± 13 burst per 100 heartbeats, P<0·0001). The difference of MSNA activity between rest and late recovery phase had a strong positive correlation with the difference in SD1 (r = 0·78, P<0·001) at equal HRs. Subjects who have a higher sympathetic activity in the recovery phase of exercise have a more augmented cardiac vagal activity resulting in an accentuated sympatho-vagal outflow. The altered autonomic interaction observed here may partly explain the clustering of various cardiovascular events to the recovery phase of exercise.     

Synthesis of cyanopyridine and pyrimidine analogues as new anti-inflammatory and antimicrobial agents

A new series of substituted benzylidene acetophenone (Ia-Ih), 2-amino-4, 6- substituted diphenylpyridine-3-carbonitrile (IIa-IIh) and 4, 6-substituted diphenylpyrimidin-2-amine (IIId-IIIg) were synthesized and evaluated for anti-inflammatory and antimicrobial activities. Four compounds (Ie, If, IIh and IIId) have shown good anti-inflammatory activity when compared to standard drug indomethacin. Two compound (Ie and IIh) displayed significant activity against gram -ve bacteria (E. Coli) and three compounds (IId, IIf and IIIh) displayed good activity against gram +ve bacteria (S. aureus) on comparison with the standard drug ofloxacin.     

世界卫生组织身体活动政策和指南的架构与核心内容研究

目的 研究分析身体活动政策和身体活动指南的理论、政策架构以及核心内容。 方法 运用政策研究和内容分析的方法以及世界卫生组织(WHO)健康服务体系六大构成要素的理论,具体分析WHO身体活动全球行动计划和WHO身体活动指南的理论、架构和核心内容。结果 《2018-2030年促进身体活动全球行动计划：加强身体活动,造就健康世界》(简称《行动计划》)是WHO颁布的有关身体活动的国际政策文件,该政策文件遵循以人权、全生命周期、循证实践、比例普遍性、政策协调性和将健康融入所有政策、参与和赋权、建立多部门伙伴关系的7个原则,将身体活动纳入健康服务和社会发展的范畴。《行动计划》由4项战略目标和20项政策行动构成,涉及WHO健康服务体系六个领域,身体活动政策融入健康服务,对于促进实现联合国可持续发展目标三健康全覆盖有着十分重要的意义。2020年《WHO关于身体活动和久坐行为的指南》(简称《指南》)作为贯彻落实《行动计划》的技术文件,采用PI/ECO方法架构,分析了各类人群的身体活动需求,针对儿童与青少年、成年人、老年人, 特殊人群孕妇和产后妇女、慢病患者和残疾人士等,提出了增加身体活动和减少久坐行为的活动指南,内容涉及身体活动的持续时间、频率、强度、身体活动类型、身体活动的关键和重要的健康结果,以及预防健康风险和相关的注意事项。《指南》贯彻落实《行动计划》的相关指导原则,旨在从微观层面提升整体人群参与身体活动程度,改善提高整体人群关键和重要的健康结果。结论 作为一项健康战略和发展战略,《行动计划》倡导将身体活动纳入健康服务体系,促进实现联合国2030可持续发展目标三全民健康覆盖。根据WHO健康服务体系六大构成要素,即领导力和治理、筹资、人力资源、服务提供、医药技术、健康信息,可以将《行动计划》4项战略目标和20项政策行动纳入上述六个领域。《指南》作为贯彻落实 《行动计划》的技术文件,基于PI/ECO方法架构,针对儿童与青少年、成年人、老年人、孕妇和产后妇女、慢病人群、残疾人等人群提供增加身体活动与减少久坐行为的指南建议。核心内容涉及针对的人群、身体活动的持续时间、频率、强度、身体活动类型、身体活动的关键和重要的健康结果,以及预防健康风险和相关的注意事项。     

Biological activities of skin and parotoid gland secretions of bufonid toads (Bufo bufo,Bufo verrucosissimus and Bufotes variabilis) from Turkey

Toad glandular secretions and skin extractions contain numerous natural agents which may provide unique resources for novel drug development. Especially the skin-parotoid gland secretions of toads from genus Bufo contain as many as 86 different types of active compounds, each with the potential of becoming a potent drug. In the present study, crude skin-parotoid gland secretions from Bufo bufo, Bufo verrucosissimus and Bufotes variabilis from Turkey were screened against various cancer cells together with normal cells using MTT assay. Furthermore, the antimicrobial properties of skin secretions were tested on selected bacterial and fungal species for assessing the possible medical applications. Antimicrobial activity of skin secretions was studied by determining minimal inhibitory concentration (MIC) in broth dilution method. Hemolytic activity of each skin-secretion was also estimated for evaluating pharmaceutical potential. Both skin-parotoid gland secretions showed high cytotoxic effect on all cancerous and non-cancerous cell lines with IC₅₀ values varying between <0.1 μg/ml and 6.02 μg/ml. MIC results of antimicrobial activity tests were found to be between 3.9 μg/ml and 250 μg/ml. No hemolytic activities on rabbit red blood cells at concentrations between 0.5 μg/ml and 50 μg/ml were observed. In conclusion, skin-parotoid secretions of bufonid toads might be remarkable candidates for anti-cancer and antimicrobial agents without hemolytic activities.     

Antitubercular activities of novel benzothiazolo naphthyridone carboxylic acid derivatives endowed with high activity toward multi-drug resistant tuberculosis

Sixteen novel 3-nitro-2-(sub)-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acids were synthesized from 2,6-dimethoxynicotinic acid and 2-aminothiophenol and evaluated for their antitubercular activities in vitro and in vivo against Mycobacterium tuberculosis H₃₇ Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among the synthesized compounds, 2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acid (10n) was found to be the most active compound in vitro with MIC of 0.19 and 0.04 μM against MTB and MTR-TB, respectively. Compound 10n showed promising activity against MDR-TB and was 208 and 1137 times more potent than gatifloxacin and isoniazid, respectively. In the in vivo animal model 10n decreased the mycobacterial load in lung and spleen tissues with 2.81 and 4.94-log₁₀ protections, respectively, at a dose of 50 mg/kg body weight.