Unveiling whole‐brain dynamics in normal aging through Hidden Markov Models

During normal aging, the brain undergoes structural and functional changes. Many studies applied static functional connectivity (FC) analysis on resting state functional magnetic resonance imaging (rs‐fMRI) data showing a link between aging and the increase of between‐networks connectivity. However, it has been demonstrated that FC is not static but varies over time. By employing the dynamic data‐driven approach of Hidden Markov Models, this study aims to investigate how aging is related to specific characteristics of dynamic brain states. Rs‐fMRI data of 88 subjects, equally distributed in young and old were analyzed. The best model resulted to be with six states, which we characterized not only in terms of FC and mean BOLD activation, but also uncertainty of the estimates. We found two states were mostly occupied by young subjects, whereas three other states by old subjects. A graph‐based analysis revealed a decrease in strength with the increase of age, and an overall more integrated topology of states occupied by old subjects. Indeed, while young subjects tend to cycle in a loop of states characterized by a high segregation of the networks, old subjects'' loops feature high integration, with a crucial intermediary role played by the dorsal attention network. These results suggest that the employed mathematical approach captures the complex and rich brain''s dynamics underpinning the aging process.     

A novel vehicle for the treatment of psoriasis

This study evaluates the effectiveness of the topical use of an aerosol foam combination of calcipotriol 50 μg/g plus betamethasone dipropionate 0.5 mg/g (Cal/BD foam, Enstilar®) in adults with moderate plaque psoriasis. A total of 120 male and female adult psoriasis patients (53.3% male) from two Italian dermatological units were enrolled in an 8‐week prospective study performed between November 2018 and January 2019. Psoriasis Area and Severity Index (PASI) was evaluated at baseline (T0) and 4 weeks (T4) of daily application, and a further evaluation was carried out 4 weeks after suspension (T8). Furthermore, the Dermatology Life Quality Index (DLQI) was evaluated at baseline and after 4 weeks of treatment (T4). At baseline, patients presented a mean PASI of 7 (7.0 ± 2.1). After 4 weeks (T4) of once‐daily application, an important improvement in PASI was observed (1.1 ± 0.3). At Week 4, DLQI was reduced by 5.5 points from baseline (mean: 12 ± 3.1 at T0 vs 6.5 ± 1.8 at T4). Four weeks after suspension (T8), mean PASI was 2.6 ± 1.9, which was stable compared to the previous evaluation; only 8.3% of the treated patients showed worsening of plaque psoriasis. This study suggested that the Cal/BD aerosol foam is an effective topical therapy to treat plaque psoriasis.     

Differential 3,5,3'-triiodothyronine-mediated regulation of uncoupling protein 3 transcription: role of Fatty acids

T(3) regulates energy metabolism by stimulating metabolic rate and decreasing metabolic efficiency. The discovery of mitochondrial uncoupling protein 3 (UCP3), its homology to UCP1, and regulation by T(3) rendered it a possible molecular determinant of the action of T(3) on energy metabolism, but data are controversial. This controversy may in part be attributable to discrepancies observed between the regulation by T(3) of UCP3 expression in rats, humans, and mice. To clarify this issue, we studied 1) the induction kinetics of the UCP3 gene by T(3) in rat skeletal muscle, 2) the influence of fatty acids, and 3) the structure and regulation of the various UCP3 promoters by T(3). Within 8 h of single-dose T(3) administration, hypothyroid rats showed a rise in serum fatty acid levels concomitant with a rapid increase in UCP3 expression in gastrocnemius muscle, followed by inductions of peroxisome proliferator activated receptor delta (PPARdelta) (within 24 h) and PPAR target gene expression (after 24 h). This T(3)-induced early UCP3 expression depended on fatty acid-PPAR signaling because depleting serum fatty acid levels abolished its expression, restorable by administration of the PPARdelta agonist L165,041 (4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid). In transfected rat L6 myoblasts, only the rat UCP3 promoter positively responded to T(3) and L165,041 together in the presence of MyoD, thyroid hormone receptor beta1 (TRbeta1), PPARdelta, or PPARdelta plus the TR dimerization partner retinoid X receptor alpha. All promoters share a response element common to TR and PPAR (TRE 1), but the observed species differences may be attributable to different localizations of the MyoD response element, which in the rat maps to exon 1.     

PCT、CRP动力学评估脓毒血症预后及诊断意义的研究

目的 观察血清降钙素原(PCT)、C反应蛋白(CRP)及其动力学变化,评估其在严重脓毒症/感染性休克患者的诊断及预后价值.方法 本研究采用回顾性分析方法,2014年9月1日至2016年4月30日选择184例ICU中被诊断为严重脓毒症/感染性休克疾病患者,检测入院时血清PCT、CRP水平和治疗后第2,第3和第5天的PCT、CRP水平.结果 通过△PCT、△CRP评估PCT、CRP的动力学在存活者与死亡组中有显著性统计学意(△PCT2/0,P=0.0001;△PCT3/0,P=0.0001;△PCT5/0,P=0.0001;△CRP2/0,P=0.0069;△CRP3/0,P=0.0001;△CRP5/0,P=0.0001),在严重脓毒症和感染性休克组中也存在显著差异(PCT5,P=0.007;△PCT5/0,P=0.007).受试者工作特征曲线(ROC)模型显示,△PCT3/0(AUC=0.721)、△PCT5/0(AUC=0.77)、△CRP5/0(AUC=0.766)水平判断严重脓毒症/感染性休克患者预后有较好的临床意义.△PCT5/0 (0.619)对严重脓毒症或感染性休克有一定的辅助诊断效果,其在ROC曲线上灵敏度、特异性均较高的临界点为0.624,所以,以第5天的血清△PCT5/0水平＞0.624可作为预测感染性休克的临界点.结论 血清中PCT、CRP对严重脓毒症/感染性休克早期有较好的临床诊断及预后价值,其动力学研究可以提高对严重脓毒症/感染性休克诊断及预后评估的敏感性及准确性.     

红景天抑制人脐静脉内皮细胞生长的初步研究

目的:利用体外培养人脐静脉内皮细胞,观察中药红景天对细胞生长的影响,初步探讨急、慢性高原病患者服用中药红景天防治高原病及改善症状等的作用机制。方法:培养人脐静脉内皮细胞EVC-304,设对照组与加药组,加药组分别加入不同浓度的红景天,培养3d后计数。加药组及对照组细胞用瑞氏染料染色并拍照。收集细胞以流式细胞术检测细胞周期。结果:对照组细胞形态正常,成梭形,排列紧密,分散均匀。加药组细胞数量明显减少,细胞皱缩,聚集成团,形态各异。流式细胞术检测显示加药组G1期细胞含量增多,S期细胞减少。结论:红景天具有抑制血管内皮细胞生长的作用,可能是通过抑制细胞的增殖来抑制内皮细胞生长。抑制血管内皮细胞生长对于阻止血管内膜增生,防止形成肺动脉高压,降低慢性高原病发病率具有实际应用意义。     

酶联免疫吸附试验中HBsAg室内质控参考品的制备和应用

目的建立室内质控参考品以鉴别诊断试剂的质量和控制操作误差,提高乙型肝炎病毒表面抗原的检测准确度。方法以国家标准品为标准制备灵敏度系列参考品、特异性参考品及精密性参考品。检测其稳定性,并进行同厂家、不同批号试剂的比较及不同厂家、三批试剂的比较。结果制备的室内质控参考品在-20℃与4℃保存3～4周检测结果无统计学差异。采用同一厂家、不同批号的HBsAg诊断试剂检测室内质控参考品,结果无统计学差异。采用不同厂家、同一批号的HBsAg诊断试剂检测结果有统计学差异。结论我们建立的室内质控参考品适宜作HBsAg室内质控,提醒我们在更换试剂厂家时应特别注意室内质控参考品的变化。     

Anti-inflammatory effect of tuftsin and its retro-inverso analogue in rat adjuvant arthritis

Tuftsin, an immunostimulating tetrapeptide derived from immunoglobulin heavy chain, and its retro-inverso analogue have been tested in rat adjuvant arthritis. The secondary lesion of rats injected with Freund's adjuvant was significant inhibited by both the natural and retro-inverso tuftsin administered orally. The retro-inverso analogue was at least tenfold more potent than the parent molecule, suggesting an increased stability to degradation, because of its molecular modification. The anti-inflammatory effect of tuftsin may be due to its ability to modulate macrophage function.