• Griffin Egan opublikował 5 miesięcy, 2 tygodnie temu

    Recently, a large number of single particle tracking (SPT) approaches have been developed. Generally, SPT techniques can be split into two groups ex post facto approaches where trajectory extraction is carried out after data acquisition and feedback based approaches that perform particle tracking in real time [1]. One feedback approach is 3D Orbital Tracking, where the laser excitation beam is rotated in a circle about the object, generating a so called orbit [2,3]. By calculating the particle position from the detected intensity after every orbit in relation to its center, this method allows the microscope to follow a single object in real time. The high spatiotemporal resolution of this method and the potential to optically manipulate the followed object during the measurement promises to yield new deep insights into biological systems [4-7]. By upgrading this approach in a way that the specimen is recentered by a xy-stage on the center of the microscope, particle tracking with this long-range tracking feature is no longer limited to the covered field-of-view. This allows for the observation of mitochondrial trafficking in living zebrafish embryos over long distances. Here, we provide the raw data for antero- and retrograde movement of mitochondria labelled with photo-activatable green fluorescent protein (mitoPAGFP). It relates to the scientific article „Nanoresolution real-time 3D orbital tracking for studying mitochondrial trafficking in vertebrate axons in vivo” [8]. By applying a correlation analysis on the trajectories, it is possible to distinguish between active transport and pausing events with less biasing compared to the mean squared displacement approach. © 2020 The Authors.Today’s treatment for chronic pain is inadequate, and novel targets need to be identified. This requires a better understanding of the mechanisms involved in pain sensitization and chronification. In this review, we discuss how peripheral inflammation, as occurs during an infection, modulates the central pain system. In rodents, neonatal inflammation leads to increased pain sensitivity in adulthood by priming immune components both peripherally and centrally. The excitability of neurons in the spinal cord is also altered by neonatal inflammation and may add to pain sensitization later in life. In adult humans, inflammation modulates pain sensitivity as well, partly by affecting the activity in brain areas that process and regulate pain signals. Low-grade inflammation is common in clinical populations both peripherally and centrally, and priming of the immune system has also been suggested in some pain populations. The nociceptive and immune systems are primed by infections and inflammation. The early life programming of nociceptive responses following exposure to infections or inflammation will define individual differences in adult pain perception. Immune-to-brain mechanisms and neuroimmune pathway need further investigation as they may serve both as predictors and therapeutic targets in chronic pain.Objectives In this study, we used a discrete choice experiment (DCE) conducted August-October 2017 to examine electronic nicotine delivery systems (ENDS) product preferences in a national sample of adult smokers (N = 1154) who were also using ENDS or had not ruled out future use. Methods The DCE evaluated 5 ENDS attributes relative harm; effectiveness for helping smokers quit; nicotine strength; flavor; and price. We asked participants to choose among their own cigarettes, 2 ENDS products whose attributes varied across tasks, or none. We analyzed ENDS preferences using multinomial, nested, and mixed logit regressions. Results Smokers preferred ENDS that are less harmful than cigarettes, are effective in helping smokers quit, are lower priced, and are not menthol-flavored. The marginal willingness to pay for an ENDS product was $8.40 when less harmful than cigarettes, $4.13 when of unknown effectiveness in helping quitting ($13.90 when effective), and $3.37 when ENDS are not menthol-flavored. Furthermore, the overall flavor preference is driven by tobacco smokers, not by menthol cigarette smokers who do prefer menthol-flavored ENDS. Conclusions Policies that affect perceptions of ENDS effectiveness in promoting cessation and their relative harm may alter smokers’ ENDS preferences. Regulating flavors and price also may influence adult smokers’ ENDS preference.U.S.-born citizens are victims of human trafficking typically exploited through sex trafficking. At least some of them interact with healthcare providers during their trafficking experience; yet a majority goes unidentified. Although protocols and training guides exist, healthcare providers often do not have the necessary skills to identify and assist victims of sex trafficking. Understanding where victims seek care and barriers for disclosure are critical components for intervention. Thus, this study interviewed survivors of sex trafficking to ascertain a) healthcare settings visited during trafficking, b) reasons for seeking care, and c) barriers to disclosing victimization. An exploratory concurrent mixed-methods approach was utilized. Data were collected between 2016-2017 in San Diego, CA and Philadelphia, PA (N = 21). Key findings 1) Among healthcare settings, emergency departments (76.2%) and community clinics (71.4%) were the most frequently visited; 2) medical care was sought mainly for treatment of STIs (81%); and 3) main barriers inhibiting disclosure of victimization included feeling ashamed (84%) and a lack of inquiry into the trafficking status from healthcare providers (76.9%). Healthcare settings provide an opportunity to identify victims of sex trafficking, but interventions that are trauma-informed and victim-centered are essential. These may include training providers, ensuring privacy, and a compassionate-care approach.Ribosome profiling provides information on the position of ribosomes on mRNA on a genomic scale. Although this information is often used to detect changes in gene expression under different conditions, it also has great potential for yielding insight into the mechanism and regulation of protein synthesis itself. First developed in yeast, ribosome profiling involves the isolation and sequencing of ribosome-protected mRNA fragments generated by nuclease treatment. Since the application of ribosome profiling in bacteria has been problematic, we report here a systematically optimized protocol for E. coli that we have used with success for other bacteria as well. Cells are harvested by flash-freezing cultures directly in liquid nitrogen. After lysis, translation is arrested by high magnesium concentration without the use of antibiotics. These improvements eliminate artifacts induced by harvesting cells by centrifugation or filtration and by use of chloramphenicol to arrest translation. These improvements are especially appropriate for studies where the exact position of the ribosome is critical, and not merely the number of ribosomes per message, such as studies aimed at monitoring differences in local elongation rates.Precise and reproducible isolation of desired cell types or layers from heterogeneous tissues is crucial to analyze specific gene profiles and molecular interactions in vivo. Forebrain is the core site of higher functions, like cognition and memory consolidation. It is composed of heterogeneous and distinct cell types, interconnected to form functional neural circuits. Any alteration in the development or function often leads to brain disorders with profound consequences. Thus, precise molecular understanding of forebrain development in normal and diseased scenarios is important. For quantitative studies, most traditional analytical methods require pooling of large cell populations, that results in loss of in vivo tissue integrity and of spatial, molecular and cellular resolution. Laser capture microdissection (LCM) is a fast and extremely precise method of obtaining uncontaminated, homogeneous sets of specific cell types and layers. Our current procedure involves cryo-sectioning and laser microdissection of fresh-frozen mouse forebrains, that are genetically modified and treated with small-molecule therapeutics. Using LCM, specific regions of interest, such as neural layers, cells from adjacent yet distinct subregions within a tissue layer, are obtained under RNase-free conditions. These small cellular cohorts are further used for downstream, high-throughput genomic or transcriptomic assays. Here, we have introduced break-points at multiple stages throughout our protocol. This makes our method simpler and more user-friendly to follow, without compromising on the quality. The current protocol can easily be adapted for different brain regions, as well as for other model organisms/human tissue.Immunotherapy with immune checkpoint inhibitors (ICIs), while ameliorating lung cancer, can cause infectious diseases, including tuberculosis, in addition to immune-related noninfectious complications. In the clinical setting, the efficacy of ICIs to treat mycobacterial infection remains controversial. We report 3 cases of acute Mycobacterium avium complex lung disease during immunotherapy with ICIs. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown. Methods This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture. Results Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P  less then  .001), echocardiography (79% vs 45%; P  less then  .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P  less then  .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P  less then  .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76). Conclusions Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Human babesiosis is a common zoonosis caused by Babesia and is attracting an increasing concern worldwide. The natural course of babesiosis infection and how the human immune system changes during the course of babesiosis infection are not clear. Methods We followed up 1 case infected with Babesia venatorum for 5 years. The patient was immune-intact and received no standard treatment. Clinical data were obtained from medical records. Microbiological tests, ribonucleic acid (RNA) sequence, and serum cytokines and chemokines were detected at different time points. Results The patient was confirmed as B venatorum infection based on his tick-bite history, clinical manifestations, and positive results of microbiological tests. The parasitemia of the patient persisted for approximately 2 months. With flu-like symptoms aggravating, most cytokines and chemokines in RNA and protein levels increased progressively and reached the peak when fever occurred; and their concentrations decreased to baseline during the same time as clearance of babesia parasites. Conclusions Babesia venatorum infection could take a mild self-limited course in immune-intact individuals. The natural changes of most cytokines and chemokines demonstrated very similar trends, which correlated with blood parasitemia and clinical manifestations. Cytokine profiles involving multiple inflammatory cytokines might be a good indicator of babesia infection. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background This study was done to determine the burden of invasive Staphylococcus aureus on the White Mountain Apache Tribal lands. Methods Active population and laboratory-based surveillance for invasive S aureus infections was conducted from May 2016 to April 2018. A case was defined as a Native American individual living on or around the White Mountain Apache Tribal lands with S aureus isolated from a normally sterile body site. Results Fifty-three cases were identified. Most cases were adults (90.6%) and had ≥1 underlying medical condition (86.8%), the most common of which were diabetes (49.1%) and obesity (41.5%). A total of 26.4% cases were categorized as community acquired. Most infections were methicillin-resistant (75.5%). A total of 7.5% of cases required amputation, and 7.7% of cases died within 30 days of initial culture. The incidence of invasive S aureus was 156.3 per 100 000 persons. The age-adjusted incidence of invasive methicillin-resistant S aureus was 138.2 per 100 000 persons. Conclusions This community has a disproportionately high burden of invasive methicillin-resistant S aureus compared with the general US population. Interventions are urgently needed to reduce the morbidity and mortality associated with these infections. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Hansen’s disease (HD) is rare in the United States, but a steady number of cases are diagnosed annually, especially in southern areas where armadillos are present. Challenges associated with erythema nodosum leprosum (ENL), a complication of multibacillary leprosy, call for novel regimens. We present a case of a man with recalcitrant ENL from HD likely acquired in the United States. He required a combination of 4 drugs to control chronic ENL. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background The World Health Organization (WHO) estimates 127 million new cases of Chlamydia trachomatis (CT), 87 million new cases of Neisseria gonorrhea (NG), and 156 million new cases of Trichomonas vaginalis (TV) each year, which corresponds to 355 (219-606), 303 (216-468), and 243 (97.6-425) thousand disability-adjusted life-years. In low-resource settings, however, sexually transmitted infections (STIs) are treated syndromically and many individuals with asymptomatic infection may be missed, especially adolescents and young adults with human immunodeficiency virus (HIV). Methods We enrolled patients aged 15-24 with HIV (N = 300) attending a family-centered HIV clinic in Mbabane, Eswatini. Participants completed a sexual history questionnaire and provided urine as well as oropharyngeal and/or vaginal swabs, if sexually active, for testing with Xpert CT/NG and TV tests. Analysis included bivariate and multivariate odds ratios and test sensitivity and specificity. Results Sexually transmitted infection rates were highest (25.0%; 95% confidence interval [CI], 15.2-37.3) in females ages 20-24 who were ever sexually active. In patients with confirmed STIs, NG (15 of 32, 47%) was more common than CT (9 of 32, 28%) and TV (8 of 32, 25%). Syndromic screening alone had a sensitivity of 32.0% (95% CI, 14.9-53.3) and specificity of 86.0% (95% CI, 79.0-91.4) but varied by gender. The presence of an STI was associated with reporting new sexual partner(s) (OR = 2.6; 95% CI, 1.1-6.4), sometimes to never using condoms (OR = 4.2; 95% CI, 1.7-10.2), most recent sexual partner >25 years old (OR = 3.2; 95% CI, 1.3-7.9), and HIV diagnosis at age ≥15 years (OR = 3.4; 95% CI, 1.4-8.2). Conclusions Syndromic screening alone performed poorly. Routine diagnostic testing significantly increases STI detection and should be considered in high-risk populations, such as adolescents and young adults with HIV. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Introduction Myocardial ischemia is an early clinical indicator of several underlying cardiac pathologies, including coronary artery disease, Takatsobu cardiomyopathy, and coronary artery dissection. Significant progress has been made in computing body-surface potentials from cardiac sources by solving the forward problem of electrocardiography. However, the lack of in vivo studies to validate such computations from ischemic sources has limited the translational potential of such models. Methods To resolve this need, we have developed a large-animal experimental model that includes simultaneous recordings within the myocardium, on the epicardial surface, and on the torso surface during episodes of acute, controlled ischemia. Following each experiment, magnetic resonance images were obtained of the anatomy and electrode locations to create a subject-specific model for each animal. From the electrical recordings of the heart, we identified ischemic sources and used the finite element method to solve a static bidomain equation on a geometric model to compute torso surface potentials. Results Across 33 individual heartbeats, the forward computed torso potentials showed only moderate agreement in both pattern and amplitude with the measured values on the torso surface. Qualitative analysis showed a more encouraging pattern of elevations and depressions shared by computed and measured torso potentials. Pearson’s correlation coefficient, root mean squared error, and absolute error varied significantly by heartbeat (0.1642 ± 0.223, 0.10 ± 0.03mV, and 0.08 ± 0.03mV, respectively). Discussion We speculate several sources of error in our computation including noise within torso surface recordings, registration of electrode and anatomical locations, assuming a homogeneous torso conductivities, and imposing a uniform „transition zone” between ischemic and non-ischemic tissues. Further studies will focus on characterizing these sources of error and understanding how they effect the study results.Activation times (AT) describe the sequence of cardiac depolarization and represent one of the most important parameters for analysis of cardiac electrical activity. However, estimation of ATs can be challenging due to multiple sources of noise such as fractionation or baseline wander. If ATs are estimated from signals reconstructed using electrocardiographic imaging (ECGI), additional problems can arise from over-smoothing or due to ambiguities in the inverse problem. Often, resulting AT maps show falsely homogeneous regions or artificial lines of block. As ATs are not only important clinically, but are also commonly used for evaluation of ECGI methods, it is important to understand where these errors come from. We present results from a community effort to compare methods for AT estimation on a common dataset of simulated ventricular pacings. ECGI reconstructions were performed using three different surface source models transmembrane voltages, epi-endo potentials and pericardial potentials, all using 2nd-order Tikhonov and 6 different regularization parameters. ATs were then estimated by the community participants and compared to the ground truth. While the pacing site had the largest effect on AT correlation coefficients (CC larger for lateral than for septal pacings), there were also differences between methods and source models that were poorly reflected in CCs. Results indicate that artificial lines of block are most severe for purely temporal methods. Compared to the other source models, ATs estimated from transmembrane voltages are more precise and less prone to artifacts.Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting mainly preterm newborns. It is characterized by unexpected onset and rapid progression with specific diagnostic signs as pneumatosis intestinalis or gas in the portal vein appearing later in the course of the disease. Therefore, we analyzed diagnostic and prognostic potential of the markers of early NEC pathogenesis, such as excessive inflammatory response (serum amyloid A (SAA)) and gut epithelium damage (intestinal and liver fatty acid-binding protein (I-FABP and L-FABP, respectively) and trefoil factor-3 (TFF-3)). We used ELISA to analyze these biomarkers in the urine of patients with suspected NEC, either spontaneous or surgery-related, or in infants without gut surgery (controls). Next, we compared their levels with the type of the disease (NEC or sepsis) and its severity. Already at the time of NEC suspicion, infants who developed NEC had significantly higher levels of all tested biomarkers than controls and higher levels of I-FABP and L-FABP than those who will later develop sepsis. Infants who will develop surgery-related NEC had higher levels of I-FABP and L-FABP than those who will develop sepsis already during the first 6 hours after the abdominal surgery. I-FABP was able to discriminate between infants who will develop NEC or sepsis and the SAA was able to discriminate between medical and surgical NEC. Moreover, the combination of TFF-3 with I-FABP and SAA could predict pneumatosis intestinalis, and the combination of I-FABP, L-FABP, and SAA could predict gas in the portal vein or long-term hospitalization and low SAA predicts early full enteral feeding. Thus, these biomarkers may be useful not only in the early, noninvasive diagnostics but also in the subsequent NEC management. Copyright © 2020 Stepan Coufal et al.Background Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. Nε-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia. Copyright © 2020 Zhengyang Bao et al.Macrophages are involved in angiogenesis, an essential process for organ growth and tissue repair, and could contribute to the pathogenesis of angiogenesis-related diseases such as malignant tumors and diabetic retinopathy. Recently, long noncoding RNAs (lncRNAs) have been proved to be important in cell differentiation, organismal development, and various diseases of pathological angiogenesis. Moreover, it has been indicated that numerous lncRNAs exhibit different functions in macrophage infiltration and polarization and regulate the secretion of inflammatory cytokines released by macrophages. Therefore, the focus of macrophage-related lncRNAs could be considered to be a potential method in therapeutic targeting angiogenesis-related diseases. This review mainly summarizes the roles played by lncRNAs which associated with macrophages in angiogenesis. The possible mechanisms of the regulatory link between lncRNAs and macrophages in various angiogenesis-related diseases were also discussed. Copyright © 2020 Yang Jia and Yedi Zhou.Aim Diabetes in children is becoming more prevalent in some countries. However, in most countries, little is known about the epidemiology of this disease. This study is aimed at estimating the prevalence of type 1 and type 2 diabetes and prediabetes among children in Vietnam and examining factors associated with the conditions. Methods A total of 2880 students aged 11-14 years old were recruited for the survey, using a school-based and nationally representative sampling frame. Capillary blood samples of participants were collected to measure fasting glucose level, using glucose meter OneTouch Verio Pro+. Diabetes and impaired fasting plasma glucose were initially diagnosed based on the cut-off points of the American Diabetes Association criteria. Diabetes status and type of diabetes of participants were confirmed at a hospital. Additionally, anthropometric and blood pressure measurements were conducted following a standardized procedure. Multivariate logistic regression was used to examine the association between outcome and independent variables. Results The overall prevalence of diabetes among the participants was 1.04‰ (three cases), with 2 cases (0.75‰) diagnosed with type 1 diabetes (one known and one newly diagnosed) and 1 case newly diagnosed with type 2 diabetes (0.35‰). The prevalence of impaired fasting glucose was 6.1%. Body mass index, place of residence, and age were found to be significantly associated with the impaired fasting glucose condition in participants. Conclusion The prevalence of type 1 and type 2 diabetes in children in Vietnam is lower than that in some other countries reported recently. However, there is a high prevalence in impaired fasting glucose, requiring attention from policymakers to take action to prevent the occurrence of the epidemic of type 2 diabetes in children in the future. Copyright © 2020 Duong H. Phan et al.Background Diabetic retinopathy (DR) is a severe complication of diabetes mellitus. DR is considered as a neurovascular disease. Retinal ganglion cell (RGC) loss plays an important role in the vision function disorder of diabetic patients. Histone deacetylase3 (HDAC3) is closely related to injury repair and nerve regeneration. The correlation between HDAC3 and retinal ganglion cells in diabetic retinopathy is still unclear yet. Methods To investigate the chronological sequence of the abnormalities of retinal ganglion cells in diabetic retinopathy, we choose 15 male db/db mice (aged 8 weeks, 12 weeks, 16 weeks, 18 weeks, and 25 weeks; each group had 3 mice) as diabetic groups and 3 male db/m mice (aged 8 weeks) as the control group. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner by characterizing the process of retinal ganglion cell variation. Results Blood glucose levels and body weights of db/db mice were significantly higher tCaspase3 expression gradually accelerated in RGCs of db/db mice. LC3B expression dynamically changed in RGCs of db/db mice. HDAC3 was positively correlated with Caspase3 expression (Discussion. We clarified the dynamic expression changes of HDAC3, Caspase3, and LC3B in retinal ganglion cells of db/db mice. Our results suggest the HDAC3 expression has a positive correlation with apoptosis and autophagy. Copyright © 2020 Yuhong Fu et al.Background Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. It affects millions of people globally. In spite of many antidiabetic drugs that are available, an adequate level of control remains challenging. Hydroxychloroquine is an immunomodulatory drug that has been used for the treatment of malaria and autoimmune diseases. There is an emerging evidence that suggests its beneficial effect against diabetes mellitus. Therefore, this systematic review is aimed at discoursing the role of hydroxychloroquine against diabetes mellitus and its potential mechanisms of actions. Methods A systematic and manual searching was carried out to retrieve relevant articles (preclinical and clinical studies) published from January 2014 to July 2019. Electronic databases including PubMed and Scopus as well as clinicaltrials.gov have been searched using different searching terms „hydroxychloroquine,” „diabetes mellitus,” „hyperglycemia,” and „insulin resistance.” The MeSH terms (PubMed) ntidiabetic effect of hydroxychloroquine. Conclusion The current review provides preliminary evidence for potential antidiabetic properties of hydroxychloroquine. Though the provided available data were promising, further clinical trials and mechanistic studies are needed to determine its long-term effects. Copyright © 2020 Dawit Zewdu Wondafrash et al.Type 2 diabetes mellitus (DM2) is a disease that reports high morbidity and mortality rates worldwide. Between its complications, one of the most important is the development of plantar ulcers. The role of the polymorphonuclear cells (PMNs) is affected by metabolic diseases like DM2. Fifteen years ago, reports about a new mechanism of innate immune response where PMNs generate some kind of webs with their chromatin were published. This mechanism was called NETosis. Also, some researchers have demonstrated that NETosis is responsible for the delay of the ulcer healing both in patients with DM2 and in animal models of DM2. Purified PMNs from healthy and DM2 human volunteers were incubated with diethylcarbamazine (DEC) and then induced to NETosis using phorbol 12-myristate 13-acetate (PMA). In a randomized blind study model, the NETosis was documented by confocal microscopy. On microphotographs, the area of each extracellular neutrophil trap (NET) formed at different times after stimuli with PMA was bounded, and the intensity of fluorescence (IF) from the chromatin dyed with 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) was quantified. PMNs from healthy volunteers showed the development of NETs at expected times according to the literature. The same phenomenon was seen in cultures of PMNs from metabolically controlled DM2 volunteers. The use of DEC one hour before of the challenge with PMA delayed the NETosis in both groups. The semiquantitative morphometric analysis of the IF from DAPI, as a measure of PMN’s capacity to forming NETs, is consistent with these results. The ANOVA test demonstrated that NETosis was lower and appeared later than expected time, both in PMNs from healthy (p ≤ 0.000001) and from DM2 (p ≤ 0.000477) volunteers. In conclusion, the DEC delays and decreases the NETosis by PMNs from healthy as well as DM2 people. Copyright © 2020 Juan C. Segoviano-Ramirez et al.Background Type 2 diabetes mellitus (T2DM) is a major public health problem associated with distress. T2DM can affect health outcomes and adherence to medications. Little is however known about the association between diabetes distress and medication adherence among patients with T2DM in Ghana. Objective The objective of the present study is twofold to estimate distress associated with T2DM and to examine its association with medication adherence. Methods A hospital-based cross-sectional study was conducted among 188 patients with T2DM recruited from a diabetes specialist outpatient clinic at the Pantang Hospital in Accra, Ghana. Data were obtained using the Problem Areas In Diabetes (PAID) scale and the Medication Adherence Report Scale. Results The findings showed that about 44.7% of the patients showed high levels of diabetes-related distress. Poor adherence to medications was recorded in 66.5% of the patients. Patients who were highly distressed had 68% lower odds of adhering to their medications compared to those who were not (OR 0.32, 95% CI 0.15-0.65). A principal component analysis revealed four areas of T2DM distress which were conceptualized as negative emotions about diabetes, dietary concerns and diabetes care, dissatisfaction with external support, and diabetes management helplessness. Conclusion Our findings suggest that diabetes distress is a significant determinant of medication adherence behaviour in patients with T2DM. Thus, incorporating routine screening for distress into the standard diabetes care within the Ghanaian health system and having health practitioners adopt holistic approaches to diabetes management will be important context-specific interventions to improve adherence and health outcomes of people living and coping with T2DM. Copyright © 2020 Irene A. Kretchy et al.Aims To investigate the effect of preoperative HbA1c levels on the postoperative outcomes of coronary artery disease surgery in diabetic and nondiabetic patients. Methods and Results The MEDLINE (via PubMed), Cochrane Library, Web of Science, Embase, Wanfang Data, China National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) databases were used to search the effects of different preoperative HbA1c levels on the postoperative outcomes of coronary artery disease surgical treatment in diabetic and nondiabetic patients from inception to December 2018. Two review authors worked in an independent and duplicate manner to select eligible studies, extract data, and assess the risk of bias of the included studies. We used a meta-analysis to synthesize data and analyze subgroups, sensitivity, and publication bias as well as the GRADE methodology if appropriate. The literature search retrieved 886 records initially, and 23 cohort studies were included in the meta-analysis. In this meta-analysis, we fal fibrillation events (OR = 0.99, 95% CI 0.74-1.33) for nondiabetic patients. The certainty of evidence was judged to be moderate or low. Conclusion This meta-analysis showed that higher preoperative HbA1c levels may potentially increase the risk of surgical site infections, renal failure, and myocardial infarction and reduce the length of hospital stay in diabetic subjects after coronary artery disease surgical treatment and increase the risk of mortality and renal failure in nondiabetic patients. However, there was great inconsistency in defining higher preoperative HbA1c levels in the studies included; we still need high-quality RCTs with a sufficiently large sample size to further investigate this issue in the future. This trial is registered with CRD42019121531. Copyright © 2020 Jinjing Wang et al.Background and Objectives. Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage renal disease across the world. Early identification of DKD is vitally important for the effective prevention and control of it. However, the available indicators are doubtful in the early diagnosis of DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. Materials and Method. This case-control study involved 44 T2DM patients. Among them, 24 participants with DKD were defined as the cases and another 20 without DKD were defined as the controls. The ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry system was applied for the assessment of the serum metabolic profiles. Comprehensive analysis of metabolomics characteristics was conducted to detect the candidate metabolic biomarkers and assess their capability and feasibility. Result A total of 11 differential metabolites, including Hexadecanoic Acid (C160), Linolelaidic Acid (C182N6T), Linoleic Acid (C182N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6-Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 204, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis. Conclusion Serum metabolites might act as sensitive and specific biomarkers for DKD early detection. Further longitudinal studies are needed to confirm our findings. Copyright © 2020 Hang Zhang et al.Aims The aims of this study were to characterize nonatrophic and atrophic gastric mucosa under conventional endoscopy and probe-based confocal laser endomicroscopy (pCLE) modes and to define quantitative diagnostic parameters for these lesions under pCLE. Method In phase I, 64 patients with gastric mucosal lesions diagnosed by gastrointestinal endoscopy were enrolled in the study. Normal mucosa and suspicious lesions were evaluated under normal white light imaging (WLI) and pCLE mode. Descriptive characteristic of gastric mucosal inflammation and atrophy under pCLE were defined according to the histology. In phase II, the criteria for nonatrophic gastritis (NAG) and chronic atrophic gastritis (CAG) under pCLE were used to diagnose the mucosal lesions in 431 patients. Diagnostic accuracy of each endoscopy modes was evaluated by measuring the concordance with histology. Result A total of 64 patients with 187 positions were enrolled in the first part of this study. According to the histological diagnosis, the vessel diameter was increased in the NAG (11.18 ± 0.1 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 μm) and CAG (13.21 ± 0.29 . Conclusion pCLE shows high potential for the diagnosis of gastric inflammation and atrophy based on quantitative criteria and has the ability to be a substitute for histology in the diagnosis of diffuse lesions in the stomach. Copyright © 2020 Xiaoyun Yu et al.Numerous grading scales have been proposed to predict the outcome of aneurysmal subarachnoid hemorrhage (SAH); however, these have not been validated in angiogram-negative SAH patients. In this study, we aim to validate and compare the aneurysmal SAH grading scales in angiogram-negative SAH patients. There were 190 angiogram-negative SAH patients analyzed from January 2014 to December 2015. The outcomes were measured by delayed cerebral ischemia (DCI) and poor outcome (defined as modified Rankin Scale (mRS) 3-6 or 4-6). The predictive performance of the grading scales was assessed via evaluation of distribution, trend, association, and discrimination. In regard to the distribution, none of the patients were categorized as HAIR 8 and SAH score 8. Both grading scales indicated a significant trend between scores and outcome (P 0.750) for DCI. The predictive accuracy in each scale performed well in predicting poor outcome, with the exception of mFS and the Subarachnoid hemorrhage Early Brain Edema Score (SEBES). However, the mFS performed with increased accuracy when predicting mRS 4-6. The VASOGRADE, HAIR, and WFNS may be valuable prognostic tools for predicting both DCI and poor outcome. The mFS can be applicable for predicting DCI and mRS 4-6. The SAH score and the Hunt-Hess were also optimal for predicting poor outcome. The predictive performance of SEBES was relatively poor compared to the other scales. Copyright © 2020 Yuanjian Fang et al.Dengue is the most important mosquito-borne viral infection in Sri Lanka causing an enormous social and economic burden in the country. In the absence of therapeutic drugs and the developed vaccines are under investigation, vector control is the best strategy to reduce the disease transmission. Therefore, the development of novel tools to control dengue vector mosquitoes has become the need of the hour. Novaluron is a recently developed Insect Growth Regulator (IGR) which inhibits chitin synthesis in immature stages of insects. The aim of the study was to identify the efficacy of a simple and cost-effective Autocidal Gravid Ovitrap (AGO) developed using Novaluron to control dengue outbreaks in the District of Gampaha, Sri Lanka. Laboratory and semifield experiments were performed to identify the activity range, optimum field dosage, and residual effects of Novaluron following the World Health Organization guidelines, and field experiments were performed in the Ragama Medical Officer of Health (MOH) area. Two be supportive to local health authorities to enhance the efficiency of future vector control programs. Copyright © 2020 Gayan P. Withanage et al.Purpose The purpose of this study was to evaluate various objective, quantitative, time-resolved fluoroscopic imaging parameters for use in the peri-interventional evaluation of stenotic peripheral arterial disease lesions. Material and Methods. Ten patients (median age, 64; age range, 52 to 79; 8 males, 2 females) with high-grade stenoses of either the superficial femoral or popliteal arteries who underwent endovascular treatment were included. During each intervention, two series of intraprocedural fluoroscopic images were collected, one preintervention and one postintervention. For each imaging series, four regions of interest (ROIs) were defined within the vessel lumen, with two ROIs being proximal (ROIs 1 and 2) and two being distal (ROIs 3 and 4) to the stenosis. The time-density curve (TDC) at each ROI was measured, and the resulting area under the curve (AUC), full width at half maximum (FWHM), and time-to-peak (TTP) were then calculated. Results The analysis of the TDC-derived parameters demonstratedatient outcomes. This retrospective study was approved by the local ethics committee under the Number 372/2018BO2. The trial was registered at the German clinical trials register under the number DRKS00017813. Copyright © 2020 Patrick Ghibes et al.Introduction. In the field of orthopaedic surgery, the use of osteogenic material in larger defects is essential. Autograft and allograft are both known methods, and autograft is believed to be the best choice. But autograft is associated with additional invasive procedures which can prove difficult in fragile patients and can cause local side effect after bone harvest. For feasible purposes, the use of allograft is hereby rising and comparing efficacies, and the differences between autograft and allograft are essential for the clinical outcome for the patients. Method 24 female Norwegian brown rats were included, 12 normal rats and 12 induced with osteoporosis (OP). OP inducement was verified in vivo by bone volume fraction (BV/TV) at 90 days after ovariectomy (OVX). The primary surgery in each rat consisted of a 2.5 × 3 mm hole in the proximal tibia, bilaterally. Autograft and allograft were randomly allocated in the right and left tibia. After an observation of 21 days, the rats were sacrificed. Tibia samples were harvested, micro-CT scanned for bone inducement and microarchitectural properties, and then embedded for histology. Results The OP induction was verified three months after the OVX by a reduction of 68.5% in the trabecular bone BV/TV compared to normal bone. Microarchitectural analysis and histology showed no significant differences in the bone-forming capabilities between autograft and allograft in normal or osteoporotic bone after 3 weeks. Conclusion This study did not demonstrate any difference between autograft and allograft in a normal or osteoporotic rat tibial defect model after 21 days, suggesting allograft is a good alternative to autograft. Copyright © 2020 Chris H. Dreyer et al.Association of Coagulation factor V (F5) polymorphisms with the occurrence of many types of cancers has been widely reported, but whether it is of prognostic relevance in some cancers remain to be resolved. The RNA-sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA). The potential of F5 genes to predict the survival time of gastric cancer (GC) patients was investigated using univariate and multivariate survival analysis whereas „Kaplan-Meier plotter” (KM-plotter) online tools were employed to validate the outcomes. TCGA data revealed that F5 mRNA levels were significantly upregulated in gastric cancer samples. Survival analysis confirmed that high levels of F5 mRNA correlated with short overall survival (OS) in gastric cancer patients, and the area under the curve (AUC) values of 1-, 2-, and 5-year OS rate were 0.554, 0.593, and 0.603, respectively. Survival analysis by KM-plotter indicated that the high expression of F5 mRNA was significantly associated with a shorter OS compared with the low expression level in all patients with GC, and this was also the case for patients in stage III (hazard ratio (HR) = 1.78, P = 0.017). These findings suggest that the F5 gene is significantly upregulated in GC tumour tissues, and may be a potential prognostic biomarker for GC. Copyright © 2020 Yi Liu et al.Isoliquiritigenin (ILQ) is a natural product isolated from licorice root which has served as traditional Chinese medicine for a long time. Recently, the antitumor effects of ILQ have been widely studied in various cancers, but the role and related mechanisms of ILQ in esophageal squamous carcinoma cells (ESCC) are still poorly understood. In our studies, ILQ showed profound antitumor activities in ESCC cells. In vitro, ILQ substantially inhibited cell proliferation and anchorage-independent growth in a panel of human ESCC cells. Mechanism studies showed that EGFR signaling pathway played an important role for ILQ to exert its antitumor activity in ESCC. Exposure to isoliquiritigenin substantially decreased EGF-induced EGFR activation and its downstream Akt and ERK1/2 signaling pathway. EGFR knockdown with shRNA in ESCC cell significantly reduced the sensitivity of cancer cells to ILQ. Moreover, it was found that ILQ had a significantly inhibitory effect on AP-1 family, the protein of Jun and Fos subfamilies was substantially downregulated, and the transcriptional activity of AP-1 family was dramatically suppressed by ILQ. By reducing the expression of cyclin D1, ESCC cells were induced G0/G1 arrest, and cell division was substantially blocked. Finally, the antitumor potency of ILQ was validated in xenograft models and the tumor growth was prominently restrained by ILQ. Briefly, our study showed that ILQ, or its analogue, appeared to be a promising new therapeutic agent for ESCC management. Copyright © 2020 Liping Ye et al.Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes. Copyright © 2020 Xiao-Xiao Li et al.Objective We studied bone marrow plasma (BMP) cytokines in severe aplastic anemia (SAA) patients and healthy volunteers to investigate differences in the cytokine profiles between them and propose a cytokine signature of SAA. Methods A Bio-Plex suspension array system was used to measure 27 analytes in BMP samples from 47 SAA patients and 30 healthy donors. Results Compared to healthy people, SAA patients had higher levels of tumor necrosis factor α (TNF-α (TNF-γ (IFN-γ (IFN-β (MIP-1β (MIP-1α (TNF-α (TNF-β (MIP-1β (MIP-1β (MIP-1γ (IFN-α (TNF. Conclusions The current study demonstrated distinct cytokine profiles among untreated SAA patients, recovering SAA (RSAA) patients, and healthy people. The cytokines of RSAA patients showed similar characteristics to those of untreated SAA patients and healthy people, respectively, which may reflect that the immune status of RSAA patients is in different stages of recovery after IST; thus, it may provide an important tool in diagnosing and evaluating or predicting curative effects in clinics. Copyright © 2020 Bingnan Liu et al.Objective The relationship between serum progesterone and the first trimester pregnancy outcome of threatened abortion is still controversial. Therefore, we aimed to further study the association between these two parameters. Methods The present study is an observational retrospective cohort study. A total of 726 participants who had threatened abortion from a hospital in Guangdong, China, were included in this study from 17th August 2011 to 30th October 2018. The exposure variable and the outcome variable were serum progesterone measured at baseline and early pregnancy outcome, respectively. Covariates involved in this study included patients’ basic demographics, obstetric history, and clinical information. Results A negative association and a saturation effect were detected between serum progesterone and the first trimester pregnancy outcome. When progesterone less then 90.62 nmol/L, an increase in 1 nmol/L of serum progesterone was associated with 3% decrease of the risk of miscarriage (OR 0.97, 95% CI 0.95-0.98). Conclusion There was a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L. Our findings can better assist the clinician in understanding patients’ conditions and making medical decisions. Copyright © 2020 Yongshi Deng et al.The purpose of this study is to evaluate the impact of auricular vagus nerve stimulation, applied in conjunction with an exercise treatment program, on pain and life quality in patients with fibromyalgia syndrome (FMS). To achieve the study objectives, 60 female patients between the ages 18 and 50, with diagnosed FMS according to the American College of Rheumatology (ACR) 2010 diagnostic criteria, were randomly divided into 2 groups of 30. The first group was assigned 20 sessions of a home-based exercise program, while the second group was assigned 20 sessions of auricular vagus nerve stimulation and 20 sessions of a home-based exercise program. Patients were assessed before and after the treatments using the Visual Analog Scale (VAS) for pain, Beck Depression Scale for depression, Beck Anxiety Scale for anxiety, Fibromyalgia Impact Questionnaire (FIQ) for functional evaluation, and Short Form-36 (SF-36) for life quality. In this randomized controlled trial, comparisons within the groups revealed that both groups had statistically significant improvements in pain, depression, anxiety, functionality, and life quality scores (p less then 0.

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