Effects of human parvovirus B19 VP1 unique region protein on macrophage responses

<p>Abstract</p> <p>Background</p> <p>Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage.</p> <p>Methods</p> <p>To investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed.</p> <p>Results</p> <p>In the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein.</p> <p>Conclusion</p> <p>Taken together, our experimental results suggest that B19-VP1u with sPLA2 activity affects production of IL-6, IL-1β mRNA, and MMP9 activity, possibly through the involvement of ERK1/2 and JNK signaling pathways. These findings could provide clues in understanding the role of B19-VP1u and its sPLA2 enzymatic activity in B19 infection and B19-related diseases.</p

A junctionless SONOS nonvolatile memory device constructed with in situ-doped polycrystalline silicon nanowires

In this paper, a silicon-oxide-nitride-silicon nonvolatile memory constructed on an n+-poly-Si nanowire [NW] structure featuring a junctionless [JL] configuration is presented. The JL structure is fulfilled by employing only one in situ heavily phosphorous-doped poly-Si layer to simultaneously serve as source/drain regions and NW channels, thus greatly simplifying the manufacturing process and alleviating the requirement of precise control of the doping profile. Owing to the higher carrier concentration in the channel, the developed JL NW device exhibits significantly enhanced programming speed and larger memory window than its counterpart with conventional undoped-NW-channel. Moreover, it also displays acceptable erase and data retention properties. Hence, the desirable memory characteristics along with the much simplified fabrication process make the JL NW memory structure a promising candidate for future system-on-panel and three-dimensional ultrahigh density memory applications

Anatomical Variations of Recurrent Laryngeal Nerve During Thyroid Surgery: How to Identify and Handle the Variations With Intraoperative Neuromonitoring

Recurrent laryngeal nerve (RLN) palsy is the most common and serious complication after thyroid surgery. Visual identification of the RLN during thyroid surgery has been shown to be associated with lower rates of palsy, and although it has been recommended as the gold standard for RLN treatment, it does not guarantee success against postoperative vocal cord paralysis. Anatomical variations of the RLN, such as extra-laryngeal branches, distorted RLN, intertwining between branches of the RLN and inferior thyroid artery, and non-recurrent laryngeal nerve, can be a potential cause of nerve injury due to visual misidentification. Therefore, intraoperative verification of functional and anatomical RLN integrity is a prerequisite for a safe thyroid operation. In this article, we review the literature and demonstrate how to identify and handle the anatomical variations of the RLN with the application of intraoperative neuromonitoring in the form of high resolution photography, which can be informative for thyroid surgeons. Anatomical variations of the RLN cannot be predicted preoperatively and might be associated with higher rates of RLN injury. The RLN injury caused by visual misidentification can be rare if the nerve is definitely identified early with intraoperative neuromonitoring

Association between Albuminuria and Different Body Constitution in Type 2 Diabetes Patients: Taichung Diabetic Body Constitution Study

Objective. Albuminuria in type 2 diabetes mellitus (T2DM) patients increases the risk of diabetic nephropathy, the leading cause of end-stage renal disease worldwide. Because albuminuria is modifiable, identifying relevant risk factors could facilitate prevention and/or management. This cross-sectional study investigated whether body constitution (BC) independently predicts albuminuria. Method. Patients with T2DM (n=846) received urinalysis, a blood test, and diabetic retinopathy examination. Albuminuria was defined by an elevated urinary albumin/creatinine ratio (≥30 μg/mg). BC type (Yang deficiency, Yin deficiency, and Phlegm stasis) was assessed using a body constitution questionnaire (BCQ). Traditional risk factors for albuminuria were also recorded. Odds ratios (ORs) of albuminuria for BC were estimated using multivariate logistic regression. Results. Albuminuria was more prevalent in patients with Yang deficiency or Phlegm stasis (both P<0.01). After adjustment, patients with both Yang deficiency and Phlegm stasis exhibited a significantly higher risk of albuminuria (OR = 3.037; 95% confidence interval = 1.572–5.867, and P<0.001). Conclusion. BC is strongly associated with albuminuria in T2DM patients. Using a BCQ to assess BC is noninvasive, convenient, and inexpensive and can provide information for health care professionals to identify T2DM patients who are at a high risk of albuminuria

A novel deep intronic variant strongly associates with Alkaptonuria.

Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients

Direct Radiofrequency Application Improves Pain and Gait in Collagenase-Induced Acute Achilles Tendon Injury

Radiofrequency (RF) is often used as a supplementary and alternative method to alleviate pain for chronic tendinopathy. Whether or how it would work for acute tendon injury is not addressed in the literatures. Through detailed pain and gait monitoring, we hypothesized that collagenase-induce acute tendinopathy model may be able to answer these questions. Gait parameters, including time, distance, and range of motion, were recorded and analyzed using a walking track equipped with a video-based system. Expression of substance P (SP), calcitonin gene related peptide (CGRP), and galanin were used as pain markers. Beta-III tubulin and Masson trichrome staining were used as to evaluate nerve sprouting, matrix tension, and degeneration in the tendon. Of fourteen analyzed parameters, RF significantly improved stance phase, step length, preswing, and intermediary toe-spread of gait. Improved gait related to the expression of substance P, CGRP, and reduced nerve fiber sprouting and matrix tension, but not galanin. The study indicates that direct RF application may be a valuable approach to improve gait and pain in acute tendon injury. Altered gait parameters may be used as references to evaluate therapeutic outcomes of RF or other treatment plan for tendinopathy

The relationship of muscular endurance and coordination and dexterity with behavioral and neuroelectric indices of attention in preschool children

This study investigated the associations of non-aerobic fitness (NAF) and motor competence (MC) with attention in 4–6 year-old preschoolers. The allocation of attentional resources and speed of stimulus categorization were examined using the amplitude and latency of P3 of event-related potentials respectively, while cortical activation related to general attention and task-specific discriminative processes were examined using event-related desynchronization (ERD) at lower (8–10 Hz) and upper (10–12 Hz) alpha frequencies, respectively. Seventy-six preschoolers completed NAF (muscular power, muscular endurance, flexibility, balance) and MC (coordination and dexterity, ball skills, agility and balance) test batteries. Electroencephalogram was recorded while participants performed an auditory oddball task. After controlling for age and MC, muscular endurance was positively related to P3 amplitude. MC and its coordination and dexterity sub-component were positively related to task performance, with higher levels of coordination and dexterity showing an additional association with greater upper alpha ERD between 700 and 1000 ms following stimulus onset after controlling for age and NAF. These findings suggest relationships of NAF and MC with early childhood neurocognitive function. Specifically, muscular endurance is related to the neuroinhibition in facilitating effective allocation of attentional resources to stimulus evaluation while coordination and dexterity are related to cortical activation underlying strategic attentional preparation for subsequent stimulus evaluation

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45ml/min per 1.73m2. AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 3.3) than patients with AKI but without CKD. The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge

Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging

Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16INK4A, p21CIP1/WAF1 and p27KIP1. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification