Sleep and brain morphological changes in the eighth decade of life

ObjectiveSleep is important for brain health. We analysed associations between usual sleep habits and magnetic resonance imaging (MRI) markers of neurodegeneration (brain atrophy), vascular damage (white matter hyperintensities, WMH) and waste clearance (perivascular spaces, PVS) in older community-dwelling adults.MethodWe collected self-reported usual sleep duration, quality and medical histories from the Lothian Birth Cohort 1936 (LBC1936) age 76 years and performed brain MRI. We calculated sleep efficiency, measured WMH and brain volumes, quantified PVS, and assessed associations between sleep measures and brain markers in multivariate models adjusted for demographic and medical history variables.ResultsIn 457 subjects (53% males, mean age 76 ± 0.65 years), we found: brain and white matter loss with increased weekend daytime sleep (β = −0.114, P = 0.03; β = −0.122, P = 0.007 respectively), white matter loss with less efficient sleep (β = 0.132, P = 0.011) and PVS increased with interrupted sleep (OR 1.84 95% CI, P = 0.025).ConclusionCross-sectional associations of sleep parameters with brain atrophy and more PVS suggest adverse relationships between usual sleep habits and brain health in older people that should be evaluated longitudinally.     

Clinical and neuroimaging correlates of progression of mild parkinsonian signs in community-dwelling older adults

IntroductionMild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression.Methods205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression.Results30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants.ConclusionsLower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.     

弥散张量成像在轻度认知功能障碍中的应用

轻度认知功能障碍（MCI）目前已经成为严重影响老年人健康的疾病，早期具有可逆性。近年来弥散张量成像（DTI）以其定量显示脑白质纤维束的优势，越来越多的应用于临床，成为了研究的热点。目前研究表明，MCI患者海马、穹隆、扣带回和胼胝体的DTI指标变化明显，可用于MCI的早期识别和病情评估及预测，且多个指标联用可能增加其准确性。MCI患者DTI表现与认知功能的下降程度具有相关性，尤其与记忆功能的相关性较为确定。MCI亚型中，遗忘型MCI （aMCI）发展为阿尔茨海默病（AD）的风险更高，其部分各向异性（FA）值越低、平均弥散度（ADC）值越高预示着转化为AD的可能性越大；DTI技术对AD与MCI患者脑白质的差异较为灵敏，AD的脑白质病变范围更广、程度更重。但目前关于DTI在MCI中的应用尚存在诸多问题，尚需进一步研究。     

24-h urinary sodium excretion and the risk of adverse outcomes

Abstract

Aims

The objective was to evaluate whether sodium intake, assessed with the gold standard 24-h urinary collections, was related to long-term incidence of death, cardiovascular disease (CVD) and diabetes mellitus (DM).     

Complementary,alternative, integrative and dietary therapies for children with Crohn’s disease – A systematic review

Children with diagnosed inflammatory bowel diseases such as Crohn’s disease are faced with the daunting prospect of living with a chronic disease. Besides psychological stress, children are suffering from therapy side-effects; in particular, corticosteroid therapies are problematic in the growth phase. This highlights that there is a need for less aggressive alternative therapies for children as well as adolescents living with such chronic conditions. Elemental diets are widely used and accepted therapy options. Several pediatric Crohn’s disease patients also use complementary, alternative and integrative therapies to reduce or avoid drug therapies. To survey such therapy options and their efficiency and safety, we performed a systematic literature search and screened databases (Cochrane Library, EMBASE, OvidSP, PubMed, CAMbase, CAM-QUEST, Anthromedics) from their inception to December 2019. In total, seven of 1439 studies fulfilled search criteria. Six RCTs and one retrospective controlled trial investigating elemental diets (Flexical, Elemental 028), semi-elemental diets (Pregomin), polymeric diets (Modulen IBD), whole protein based formulas, and ω-3 fatty acid supplementation were found. Data indicated that diet therapies were equal to or more effective than corticosteroid therapies when used to treat Crohn’s disease. Regrettably, we could not identify controlled studies investigating complementary, alternative and integrative medicine approaches. Our review provides an updated overview of controlled studies investigating dietary therapies used in the treatment of pediatric Crohn’s disease, and demonstrates that the current study situation does not reflect the actual use of complementary, alternative and integrative therapies. Therefore, clinical trials are necessary to estimate risks and benefits of such therapies. The review indicated that enteral diets and ω-3 fatty acid supplementation may be an effective alternative to corticosteroid treatments for children with Chron’s disease.     

Faecal calprotectin levels after rifaximin treatment in patients with irritable bowel syndrome with diarrhoea: A single-center prospective study

Background and study aimsAlthough unclear, the pathophysiology of irritable bowel syndrome (IBS) is considered to be multifactorial. Recent studies have suggested that IBS is a low-grade inflammatory bowel disease (IBD) with high faecal calprotectin (FC) levels. Rifaximin is a potential therapeutic agent for IBS with diarrhoea (IBS-D) due to its ability to decrease FC levels. This study evaluated the role of FC as a follow-up marker of IBS-D after short-course rifaximin treatment.Patients and methodsNinety-six patients with chronic diarrhoea who fulfilled the Rome IV criteria for IBS-D were enrolled in this study from outpatient clinics. After excluding 18 patients who did not complete the study due to treatment noncompliance or missing follow-up visits, 78 patients (mean age, 39.2 ± 6.9 years) with IBS-D and elevated baseline FC levels were included. An FC level of <50 μg/g was considered normal. Abdominal symptoms were assessed using a Likert scale. All patients received oral rifaximin (550 mg three times daily) for 2 weeks, followed by assessment for abdominal symptoms and FC levels; the treatment was extended to 4 weeks if FC levels remained elevated after 2 weeks of treatment.ResultsFC levels normalised in 66 (84.6%) patients, including 60 and 6 patients treated for 2 and 4 weeks, respectively. The remaining 12 (15.4%) patients with persistently elevated FC levels despite 4 weeks of treatment also showed a significant decline in their final FC levels compared with the baseline, accompanied with a significant improvement in abdominal symptoms (p = 0.001). A cutoff baseline FC value of 148.5 μg/g could predict non-responders with 100% sensitivity and 50% specificity.ConclusionShort-course oral rifaximin treatment results in FC normalisation in IBS-D patients with high baseline FC values. Therefore, FC should be considered as a biomarker of follow-up after rifaximin treatment for IBS-D.     

Expecting the Holistic Regulation from Chinese Medicine Based on the "Solar System" Hypothesis of Ischemic Heart Disease

Stenosis of the coronary artery has been considered as an essential component of ischemic heart disease (IHD). Consequently, revascularization [e.g., percutaneous coronary intervention (PCI) and coronary artery bypass] has been the primary therapeutic approach to IHD. Such strategy has indeed revolutionized the management of IHD patients. However, not all patients with myocardial ischemia have visible coronary stenosis. Moreover, cardiovascular events occur in nearly 20% patients with stable coronary artery disease who have undergone PCI. The recently proposed “solar system” hypothesis of IHD postulates that coronary stenosis is only one (albeit important) of its features. Mechanistic contribution and clinical implication of multiple pathophysiological processes beyond coronary stenosis are highlighted in this hypothesis. On the basis of a holistic regulation and individualized medicine, Chinese medicine (CM) has been used in the real-world setting to manage a variety of diseases, including IHD, for more than two thousands years. In this article, we summarize the evidence of CM that supports the “solar system” IHD hypothesis, and argue for a comprehensive approach to IHD. At the theoretical level, the central features of this approach include a holistic view of disease and human subjects, as well as individualized medicine. At the practical level, this approach emphasizes anoxia-tolerance and self-healing.     

Immunogenicity of adenovirus-derived porcine parvovirus-like particles displaying B and T cell epitopes of foot-and-mouth disease

Virus-like particles (VLPs) vaccines combine many of the advantages of whole-virus vaccines and recombinant subunit vaccines, integrating key features that underlay their immunogenicity, safety and protective potential. We have hypothesized here the effective insertion of the VP1 epitopes (three amino acid residues 21–40, 141–160 and 200–213 in VP1, designated VPe) of foot-and-mouth disease (FMDV) within the external loops of PPV VP2 could be carried out without altering assembly based on structural and antigenic data. To investigate the possibility, development of two recombinant adenovirus rAd-PPV:VP2-FMDV:VPe a or rAd-PPV:VP2-FMDV:VPe b were expressed in HEK-293 cells. Out of the two insertion strategies tested, one of them tolerated an insert of 57 amino acids in one of the four external loops without disrupting the VLPs assembly. Mice were inoculated with the two recombinant adenoviruses, and an immunogenicity study showed that the highest levels of FMDV-specific humoral responses and T cell proliferation could be induced by rAd-PPV:VP2-FMDV:VPe b expressing hybrid PPV:VLPs (FMDV) in the absence of an adjuvant. Then, the protective efficacy of inoculating swine with rAd-PPV:VP2-FMDV:VPe b was tested. All pigs inoculated with rAd-PPV:VP2-FMDV:VPe b were protected from viral challenge, meanwhile the neutralizing antibody titers were significantly higher than those in the group inoculated with swine FMD type O synthetic peptide vaccine. Our results clearly demonstrate the potential usefulness of adenovirus-derived PPV VLPs as a vaccine strategy in prevention of FMDV.     

不同类型先天性心脏病并发二尖瓣反流手术效果随访分析

目的:随访观察不同类型先天性心脏病(先心病)合并二尖瓣反流(MR)患儿术后MR的转归。方法:回顾性分析MR术后病例229例(166例行二尖瓣成形术、63例二尖瓣未处理),比较不同类型先心病合并MR患儿行心脏畸形矫正后,二尖瓣处理组与未处理组术后早期、远期MR的转归情况。结果:144例室间隔缺损(VSD)修补同时二尖瓣成形组与29例仅行VSD修补二尖瓣未处理组患儿相比,术后早期和远期MR改善率前者均高于后者;40例动脉导管未闭(PDA)合并MR组与16例主动脉缩窄(CoA)合并MR组,术后早期二尖瓣成形组MR改善率均高于未处理组(P均0.05),而术后远期二尖瓣成形组与未处理组MR改善率均无统计学差异(P0.05)。结论:不同类型先心病合并MR可能需要采取不同的处理方案。VSD合并MR者,建议在修补缺损同时对较重度MR行二尖瓣成形术;而PDA或CoA合并MR患儿可先矫正心脏畸形,再根据患儿远期预后,决定是否行二尖瓣成形术。