Background: Continuous intravenous infusion (IV) or subcutaneous injection (SC) of insulin was widely applied to control hyperglycemia after ischemic stroke. However, the impact of different ...administration modes on glycemic variability was unknown. Methods: Consecutive stroke patients treated with intravenous thrombolysis were screened. Subjects who received insulin treatment were included and entered into the IV or SC group according to the respective administration mode. Blood glucose was closely monitored within the first 72 hours, and the target range of glucose was from 7.7 to 10.0 mmol/L for all patients. The variabilities of glucose, assessed using standard deviation of the mean, variable coefficient and range from the maximum to the minimum value, were compared between the two groups. Results: A total of 130 patients were enrolled with 66 in the IV groups and 64 in the SC group. Compared with the SC group, the IV group had higher glycemic variability evaluated as either standard deviation (2.7 + or - 0.7 mmol/L vs 2.2 + or - 0.9 mmol/L, p = 0.002), variable coefficient (0.26 + or - 0.06 vs 0.23 + or - 0.08, p = 0.011) or range (10.0 + or - 3.6 mmol/L vs 8.1 + or - 3.1 mmol/L, p = 0.001). Multivariate logistic regression analyses found that continuous intravenous infusion was associated with higher level of the standard deviation (adjusted OR 3.01, 95% CI 1.29-7.28, p = 0.011), variable coefficient (adjusted OR 5.97, 95% CI 2.55-13.96, p < 0.001) and range (adjusted OR 6.08, 95% CI 2.63-14.05, p < 0.001). Conclusion: Continuous intravenous infusion of insulin was associated with higher glycemic variability than subcutaneous injection in acute stroke patients receiving thrombolysis. Keywords: acute ischemic stroke, insulin, continuous intravenous infusion, subcutaneous injection, administration mode
Successful axon regeneration in the mammalian central nervous system (CNS) is at least partially compromised due to the inhibitors associated with myelin and glial scar. However, the intracellular ...signaling mechanisms underlying these inhibitory activities are largely unknown. Here we provide biochemical and functional evidence that conventional isoforms of protein kinase C (PKC) are key components in the signaling pathways that mediate the inhibitory activities of myelin components and chondroitin sulfate proteoglycans (CSPGs), the major class of inhibitors in the glial scar. Both the myelin inhibitors and CSPGs induce PKC activation. Blocking PKC activity pharmacologically and genetically attenuates the ability of CNS myelin and CSPGs to activate Rho and inhibit neurite outgrowth. Intrathecal infusion of a PKC inhibitor, Gö6976, into the site of dorsal hemisection promotes regeneration of dorsal column axons across and beyond the lesion site in adult rats. Thus, perturbing PKC activity could represent a therapeutic approach to stimulating axon regeneration after brain and spinal cord injuries.
Abstract
Hazardous materials encountered during building renovation or demolition processes not only result in uncertainty in cost estimation and the lead time but also hampers material recyclability ...and reuse. Therefore, the paper discusses the possibility of predicting the extent of the hazardous materials, including asbestos, PCB, mercury, and CFC, through data mining techniques based on registered records. Pre-demolition audits contain observation data that can be used as a sample for statistical prediction through careful processing. By developing an innovative approach of merging data from environmental inventories with building registers, the positive ratio of remaining hazardous materials in the Gothenburg building stock can be estimated. The study highlights the challenges of creating a training dataset by completing information from the existing environmental inventory, providing new insight into digital protocol development for enhancing material circularity.
Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic ...classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.
Nucleotide-binding domain leucine-rich repeat protein (NLRP) is critical in the inflammasome-activation pathway, which is important for host survival and the clearance of
. Therefore, the influence ...of NLRP1 polymorphisms on
colonization (CdC) or infection (CDI) was analyzed.
A prospective cohort study consisted of hospitalized adults was conducted from January 2011 to January 2013. Single nucleotide polymorphisms (SNPs) of NLRP1, including rs12150220, rs2670660, rs6502867, rs878329, rs8182352, rs3744717, and rs11078571, were incorporating in analyses. The episodes of CdC and CDI were the primary and secondary outcome, respectively.
Of the total of 509 eligible patients, 376 (73.9%) had neither CdC nor CDI, 104 (21.8%) had CdC without developing CDI, and 29 (4.3%) developed CDI during the study period. Through multivariate analyses, comorbid diabetes mellitus (adjusted odds ratio AOR 1.59,
=0.04) and CC genotype in NLRP1 rs3744717 (AOR 1.70,
=0.02) were recognized as the risk factor of CdC. After adjusting the independent predictors of CDI, in terms of comorbid diabetes mellitus (AOR 3.18,
=0.005) and prior exposure to ceftazidime/ceftriaxone (AOR 2.87,
=0.04) or proton pump inhibitors (AOR 3.86,
=0.001), patients with CC+GC genotype in NLRP1, rs878329 (AOR 2.39,
=0.03) remained a higher risk of CDI.
For hospitalized adults, the association of CC genotype in NLRP1 rs3744717 and CdC as well as the CC+GC genotype in NLRP1 rs878329 and CDI was respectively evidenced. We believed the prompt identification of patients having specific genotype in NLRP1 would prevent and improve the quality of care in CDI.
Neo-tanshinlactone (1) and its previously reported analogues, such as 2, are potent and selective in vitro antibreast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, ...with a better overall yield. Structure−activity relationships studies on these compounds revealed some key molecular determinants for this family of antibreast agents. Several derivatives (19−21 and 24) exerted potent and selective antibreast cancer activity with IC50 values of 0.3, 0.2, 0.1, and 0.1 μg/mL, respectively, against the ZR-75-1 cell lines. Compound 24 was 2- to 3-fold more potent than 1 against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analogue 2 showed potent activity against a ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19−21 and 24 as clinical trial candidates is warranted.
Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for physical comorbidity. This study used a twin cohort to investigate the association between physical ...diseases and phenotypic variations of ADHD. A twin cohort enriched for ADHD and other neurodevelopmental conditions were analysed. The Attention Problems subscale of the Child Behavior Checklist/Adult Behavior Checklist (CBCL/ABCL-AP) was used to measure the participants' severity of ADHD symptoms. Physical health issues were obtained with a validated questionnaire and were tested in relation to ADHD symptom severity in a co-twin control model. Neurological problems were significantly associated with a diagnosis of ADHD. A conditional model for the analysis of within-twin pair effects revealed an inverse association between digestive problems and the severity of ADHD symptoms, after adjusting for co-existing autism spectrum disorder and ADHD medications. Our findings suggest that individuals with ADHD are susceptible to neurological problems, why a thorough neurological check-up is indicated in clinical practice for this population. In addition, health conditions of digestive system could be considered as a non-shared environmental factor for behavioral phenotypes in ADHD. It supports the possible role of gut-brain axis in the underpinnings of ADHD symptoms, at least for a subgroup of individuals with certain genetic predisposition.
Rubber cement-based material is one of the important ways of utilizing waste rubber. Fatigue failure and impact failure are the most common failure forms of concrete structures, but the low stiffness ...and low strength of rubber cement-based materials do no allow them to be used in the main bearing structure. Therefore, the use of appropriate reinforcement materials and technical methods to effectively improve the yield stiffness, bearing capacity, ductility, and energy dissipation capacity of rubber cement-based materials can not be ignored. To explore the dynamic response characteristics of rubber cement mortar (RCM) with different confine conditions, the split Hopkinson pressure bar (SHPB) cyclic impact tests of four kinds of confined RCM were carried out. Firstly, the four different confine modes of RCM were designed by using the carbon fiber reinforced polymer (CFRP) sheet and steel cylinder. Then, the SHPB test system was used to carry out the amplitude-enhanced cyclic impact tests of RCM with different confine modes. Lastly, the dynamic mechanical behavior, energy behavior, dynamic damage, and failure modes of RCM with different confine modes were compared and analysed. The results show that the end faces and side of RCM were confined effectively by using the CFRP sheet and steel cylinder, which strengthened the structural resistance of RCM. However, with the simultaneous increase in impact load and impact times, stiffness degradation still occurred due to the cumulative effect of fatigue damage. The end friction constraint of the CFRP sheet and the passive confining pressure constraint of the CFRP sheet/steel cylinder significantly improved the energy dissipation capacity and impact resistance of RCM, controlled and delayed the transverse expansion deformation and crack development of RCM, and ensured the minimum damage of RCM structure. The purpose of this paper is to provide a reference for further promoting the resource utilization of waste rubber and the practical engineering application of rubber cement-based materials.
Thirty years ago, Thorson (1966; Neth J Sea Res 3:267–293) calculated that juvenile mortality in marine bivalves could exceed 98.6%. Subsequently, juvenile mortality rates have been assumed to be ...high and to influence the evolution of life history traits. However, there have been no attempts to establish whether high juvenile mortality is common or to determine if interspecific trends in juvenile mortality exist. To address this issue, we reviewed 30 studies of age-specific mortality among bivalves, gastropods, barnacles, ascidians, bryozoans and echinoderms. High juvenile mortality is widespread among benthic marine invertebrates, with 20 of the 30 studies reporting levels of juvenile mortality >90%. Mortality is particularly high during the first moments of juvenile life, and can exceed 30% during the first day. Pooling survivorship data from all species revealed a general trend, with survivorship decreasing exponentially during the first days or weeks of juvenile life until, by the age of 4 mo, virtually all cohorts were reduced to < 20 % of their initial numbers; mortality remained low thereafter. We suggest that extreme vulnerability at the onset of juvenile life is a shared trait that is largely responsible for the survivorship trend. Natural variation within this trend would be largely due to variation in intensity of mortality factors. Predation and desiccation are well-documented causes of juvenile mortality, but the current lack of data on factors such as ultraviolet radiation, diseases, and 'internal' causes (energy depletion, developmental and physiological defects) precludes a ranking of factors as selective pressures. Methods used to quantify juvenile mortality vary considerably in the level of resolution they can achieve within the early juvenile period. Studies of early juvenile mortality should ideally monitor the fate of individuals from the onset of juvenile life, using sampling intervals ≤1 d. Mapping and imaging techniques can provide accurate results for sessile organisms, whereas mark and recapture can be effective for motile animals with limited dispersal. Early juvenile mortality has been shown to influence population abundance and distribution as well as community structure. Juvenile mortality is also expected to be an important determinant of age at maturity, but only among species maturing within 4 mo of postlarval life since mortality remains low after the age of 4 mo. A compilation of data on age at first reproduction in 92 species revealed a bimodal grouping of species: 22% of species maturing within 45 d after beginning juvenile life, and 60% maturing after at least 1 yr. The influence of juvenile mortality on age at maturity will differ substantially among these 2 groups and will therefore not be equal or directly comparable among all species. Given the magnitude of early juvenile mortality and the similarities in mortality patterns across diverse taxa and habitats, a better understanding of early juvenile mortality should help researchers to understand how population parameters are regulated and help elucidate the significance of traits that characterize populations and species.
The etiological significance of neurological disorders in autism is debated, but it is clear that they complicate support provision and clinical management, and can have negative impact on outcomes. ...This systematic review and meta-analysis explored the full range of co-occurring neurological disorders in autism. We estimated the odds of having neurological complications compared to the general population and other neurodevelopmental conditions, as well as the overall prevalence of different neurological disorders. Seventy-nine articles were eligible for the systematic review, including 28 case-control studies, 43 prevalence studies, and 8 cohort studies. Findings were heterogeneous across studies. Overall, autistic individuals were significantly more likely than the general population to exhibit epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and congenital abnormalities of the nervous system, with prevalence estimates ranging from 1.1% (0%–3.3%; hydrocephalus) to 14.2% (11.3%–17.2%; epilepsy). Epilepsy was also more common in autism than in attention-deficit/hyperactivity disorder (odds ratio 95% confidence interval = 4.06 2.81–5.88). Findings indicate that awareness of neurological disorders and neurological check-ups are indicated in autism to ensure adequate physical health care and support. Prospective studies of neurological disorders in children diagnosed with or at risk of autism might further enhance our understanding of causal pathways.
Lay abstract
Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.
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