Mass gathering events and the spread of infectious diseases: Evidence from the early growth phase of COVID-19

This paper studies the impact on reported coronavirus 2019 (COVID-19) cases and deaths in Spain resulting from large mass gatherings that occurred from March 6 to March 8, 2020. To study these outcomes, the geographic differences in the planned pre-pandemic major events that took place on these dates were exploited, which is a quasi-random source of variation for identification purposes. We collected daily and detailed information about the number of attendees at football (soccer) and basketball matches in addition to individuals participating in the Women’s Day marches across Spain, which we merged with daily data on reported COVID-19 cases and deaths at the provincial level. Our results reveal evidence of non-negligible COVID-19 cases related to the differences in the percentage of attendees at these major events from March 6 to March 8. In a typical province, approximately 31% of the average daily reported COVID-19 cases per 100,000 inhabitants between mid-March and early April 2020 can be explained by the participation rate in those major events. A back-of-the-envelope calculation suggests that this implies almost five million euros (169,000 euros/day) of additional economic cost in the health system of a typical province with one million inhabitants in the period under consideration. Several mechanisms behind the spread of COVID-19 are also examined.     

Influence of adipose tissue immune dysfunction on childhood obesity

In recent decades, a dramatic rise has been observed in the prevalence of obesity in childhood and adolescence, along with an increase in fetal microsomia rates. The increased risk of obesity during this key period in development negatively affects the health of the individual later in life. Immune cells residing and recruited to white adipose tissue have been highlighted as important factors contributing to the pathogenesis of childhood obesity. Immune dysfunction in the context of obesity begins early in childhood, which is different from the pathological characteristics and influencing factors of adipose immunity in adults. Here, we explore the current understanding of the roles of childhood and early life events that result in high risks for obesity by influencing adipose tissue immune dysfunction under the pathological condition of obesity. Such knowledge will help in determining the mechanisms of childhood and early life obesity in efforts to ameliorate chronic inflammation-related metabolic diseases.     

老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联

摘要 目的：探讨老年缺血性心力衰竭的心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡的关联性。方法：2019年12月到2021月2月,选择在本院诊治的老年缺血性心力衰竭115例作为心衰组,同期选择在本院体检的非心血管疾病老年人群115例作为对照组。检测心脏DNA甲基化编码重编程、心肌细胞焦亡、铁死亡指标表达情况并进行相关性分析。结果：心衰组的心脏DNA甲基化编码重编程指标-miR-92a、miR-130a相对表达水平高于对照组（P<0.05）。心衰组的Caspase-1蛋白、Caspase-4蛋白相对表达水平高于对照组（P<0.05）。心衰组的铁调素含量高于对照组（P<0.05）。在两组230例入选者中,Spearsman相关分析显示：缺血性心力衰竭与miR-92a、miR-130a、半胱氨酸蛋白酶1（Caspase-1）、半胱氨酸蛋白酶4（Caspase-4）、铁调素存在正向相关性（P<0.05）。Logistic回归分析显示：miR-92a、miR-130a、Caspase-1、Caspase-4、铁调素为导致缺血性心力衰竭发生的重要因素（P<0.05）。结论：老年缺血性心力衰竭患者多伴随有心脏DNA甲基化编码重编程与心肌细胞焦亡、铁死亡,后三者与缺血性心力衰竭的发生存在关联性,也是导致缺血性心力衰竭发生的重要因素。     

西那卡塞联合碳酸司维拉姆对血液透析并发继发性甲状旁腺功能亢进患者钙磷代谢、FGF23/Klotho轴和心血管事件的影响

摘要 目的：观察西那卡塞联合碳酸司维拉姆对血液透析并发继发性甲状旁腺功能亢进（SHPT）患者钙磷代谢、成纤维细胞生长因子23（FGF23）/Klotho轴和心血管事件的影响。方法：选取2018年3月-2020年5月新疆医科大学第一附属医院收治的200例血液透析并发SHPT患者,根据随机数字表法分成观察组（n=100）与对照组（n=100）。对照组患者接受碳酸司维拉姆治疗,观察组患者接受西那卡塞联合碳酸司维拉姆治疗,两组患者均连续治疗3个月。观察两组疗效以及钙磷代谢指标、全段甲状旁腺激素（iPTH）、甲状旁腺体积、FGF23、Klotho水平变化,记录治疗期间发生的心血管事件。结果：观察组的临床总有效率较对照组高（P<0.05）。治疗后两组血钙升高,血磷、钙磷乘积下降（P<0.05）,且观察组治疗后血钙较对照组高,血磷、钙磷乘积较对照组低（P<0.05）。两组治疗后血清iPTH水平下降,甲状旁腺体积缩小,且观察组的变化程度较对照组大（P<0.05）。两组治疗后Klotho水平升高,FGF23水平下降,且观察组的变化程度大于对照组（P<0.05）。观察组的非致死性心血管事件发生率明显低于对照组（P<0.05）。结论：西那卡塞联合碳酸司维拉姆治疗血液透析并发SHPT患者疗效显著,可调节钙磷代谢,降低血清iPTH水平,缩小甲状旁腺体积,调节Klotho、FGF23水平,降低非致死性心血管事件发生率。     

Initial contact and toe off event identification for rearfoot and non-rearfoot strike pattern treadmill running at different speeds

The purpose of this study was to determine the validity of kinematic based initial contact (IC) and toe-off (TO) identification algorithms for rearfoot and non-rearfoot runners across a broad range of treadmill running speeds. 14 healthy active participants completed six 20–60 s treadmill running trials at 6 speeds: 2.24, 2.68, 3.13, 3.58, 4.02, and 4.48 ms⁻¹. 3D kinematic data were collected for the last 20 s of each trial. Force plates (FP) were used as the gold standard to determine ICFP and TOFP for each step. Three algorithms for finding IC, IC_Milner, IC_Alvim, IC_Alvim-mod, and one algorithm for finding toe off, TO_Fellin, were chosen for analysis. Root mean square errors (RMSE) and difference scores with 95% confidence intervals were computed for IC, TO and stance time (ST). IC_Alvim RMSE ranged from 0.175 to 0.219 s. ST_Alvim RMSE ranged from 0.168 to 0.216 s. IC_Alvim-mod RMSE ranged from 0.105 to 0.131 s. ST_Alvim-mod RMSE ranged from 0.108 to 0.129 s. IC_Milner RMSE ranged 0.012 to 0.015 s. ST_Milner RMSE ranged 0.019 to 0.024 s. IC_Milner accuracy was inversely related to speed. IC_Milner corrected with a linear regression equation reduced differences to- 0.006 ± 0.012 s with 86% of foot strikes identified within 20 ms and 58% with 10 ms. TO_Fellin RMSE ranged from 0.012 to 0.016 s. IC_Milner adjusted for speed and TO_Fellin can be used to predict IC and TO within a broad range of treadmill running speeds (2.24–4.48 ms⁻¹) and for rearfoot and non-rearfoot strikers.     

Genetic diversity of Colletotrichum gloeosporioides species complex associated with Citrus wither‐tip of twigs in Tunisia using microsatellite markers

Anthracnose Citrus disease has been associated with several symptoms worldwide and it is recently compromising Citrus production in the Mediterranean area. Four species complexes are mainly involved: Colletotrichum boninense, C. acutatum, C. gloeosporioides and C. truncatum. In this study, we investigated the genetic diversity of Colletotrichum spp. in Tunisia associated with wither‐tip of twigs on Citrus. Specific primers ITS4‐CgInt allowed the identification of C. gloeosporioides species complex in all the 54 isolates, sampled from three regions and four Citrus species. Overall, our genotypic analysis using 10 SSR markers showed a moderate diversity level in Tunisian C. gloeosporioides population and highlighted that C. gloeosporioides reproduce mainly clonally. In addition, heterothallic isolates were present in our population, suggesting that the pathogen population may undergo parasexual recombinations. The highest genetic diversity in C. gloeosporioides was recorded in Nabeul and on orange, which likely constitutes the area and the host of origin for the Citrus anthracnose disease in Tunisia. In addition, no population subdivision was detected at the geographic, host species or cultivars’ origin levels. However, our study identified two genetic subpopulations and indicated a rapid C. gloeosporioides population change at temporal scale that should be further examined over several consecutive growing seasons in order to understand its population dynamics.     

Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.     

Characterization of the blood-brain barrier choline transporter using the in situ rat brain perfusion technique

Choline enters brain by saturable transport at the blood-brain barrier (BBB). In separate studies, both sodium-dependent and passive choline transport systems of differing affinity have been reported at brain capillary endothelial cells. In the present study, we re-examined brain choline uptake using the in situ rat brain perfusion technique. Saturable brain choline uptake from perfusion fluid was best described by a model with a single transporter (V:(max) = 2.4-3.1 nmol/min/g; K(m) = 39-42 microM) with an apparent affinity (1/Km)) for choline five to ten-fold greater than previously reported in vivo, but less than neuronal 'high-affinity' brain choline transport (K(m) = 1-5 microM). BBB choline uptake from a sodium-free perfusion fluid using sucrose for osmotic balance was 50% greater than in the presence of sodium suggesting that sodium is not required for transport. Hemicholinium-3 inhibited brain choline uptake with a K(i) (57 +/- 11 microM) greater than that at the neuronal choline system. In summary, BBB choline transport occurs with greater affinity than previously reported, but does not match the properties of the neuronal choline transporter. The V:(max) of this system is appreciable and may provide a mechanism for delivering cationic drugs to brain.     

Ischemic preconditioning ameliorates microcirculatory disturbance through downregulation of TNF-alpha production in a rat cremaster muscle model

Ischemia-reperfusion (I/R) injury is a complex process involving the generation and release of inflammatory cytokines, and the accumulation and infiltration of neutrophils and macrophages, which disturbs the microcirculatory hemodynamics. Nonetheless, ischemic preconditioning (IPC) is known to produce immediate tolerance to subsequent prolonged I/R insults, although its underlying mechanism largely remains unknown. Our study investigated the role of the IB--NF-B-TNF- (tumor necrosis factor-) pathway in IPC's ability to ameliorate I/R-induced microcirculatory disturbances in rat cremaster muscle flaps. Male Sprague-Dawley rats were randomized (n=8 per group) into 3 groups: a sham-operated control group, an I/R group (4 h of pudic epigastric artery ischemia followed by 2 h of reperfusion), and an IPC+I/R group (3 cycles of 10 min of ischemia followed by 10 min reperfusion before I/R). Intravital microscopy was used to observe leukocyte/endothelial cell interactions and quantify functional capillaries in cremaster muscles. I/R markedly increased the number of rolling, adhering, and migrating leukocytes. It was also observed that I/R significantly increased TNF- expression in these injured tissues. On the other hand, IPC prevented I/R-induced increases in leukocyte rolling, adhesion, and transmigration. Moreover, TNF- protein production and its mRNA expression were downregulated in the IPC group. Finally, I/R-induced IB- phosphorylation and NF-B (p65) nuclear translocation were both suppressed by IPC. These results indicated that IPC attenuated NF-B activation and subsequently reduced TNF- expression, which resulted in the amelioration of microcirculatory disturbances in I/R-injured cremaster muscles.     

The Carboxylesterase Gene Family from <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>

Carboxylesterases hydrolyze esters of short-chain fatty acids and have roles in animals ranging from signal transduction to xenobiotic detoxification. In plants, however, little is known of their roles. We have systematically mined the genome from the model plant Arabidopsis thaliana for carboxylesterase genes and studied their distribution in the genome and expression profile across a range of tissues. Twenty carboxylesterase genes (AtCXE) were identified. The AtCXE family shares conserved sequence motifs and secondary structure characteristics with carboxylesterases and other members of the larger / hydrolase fold superfamily of enzymes. Phylogenetic analysis of the AtCXE genes together with other plant carboxylesterases distinguishes seven distinct clades, with an Arabidopsis thaliana gene represented in six of the seven clades. The AtCXE genes are widely distributed across the genome (present in four of five chromosomes), with the exception of three clusters of tandemly duplicated genes. Of the interchromosomal duplication events, two have been mediated through newly identified partial chromosomal duplication events that also include other genes surrounding the AtCXE loci. Eighteen of the 20 AtCXE genes are expressed over a broad range of tissues, while the remaining 2 (unrelated) genes are expressed only in the flowers and siliques. Finally, hypotheses for the functional roles of the AtCXE family members are presented based on the phylogenetic relationships with other plant carboxylesterases of known function, their expression profile, and knowledge of likely esterase substrates found in plants.