Black carp vasa identifies embryonic and gonadal germ cells

Abstract

Identification of molecular markers is an essential step in the study of germ cells. Vasa is an RNA helicase and a well-known germ cell marker that plays a crucial role in germ cell development. Here, we identified the Vasa homolog termed Mpvasa as the first germ cell marker in black carp (Mylopharyngodon piceus). First, a 2819-bp full-length Mpvasa complementary DNA (cDNA) was cloned by PCR using degenerated primers of conserved sequences and gene-specific primers. The Mpvasa cDNA sequence encodes a 637-amino acid protein that contains eight conserved characteristic motifs of the DEAD box protein family, and shares high identity to grass carp (81%) and zebrafish (74%) vasa homologs. Second, Mpvasa expression was restricted to the gonad in adulthood by RT-PCR and Western blot analysis. The dynamic patterns of temporal-spatial expression of Mpvasa during gametogenesis were examined by in situ hybridization, and Mpvasa transcripts were strictly detected in gonadal germ cells throughout oogenesis, predominantly in immature oocytes (stage I, II, and III oocytes). Third, Mpvasa transcripts were highly detected in unfertilized eggs and early embryos, and the signal indicated a dynamic migration of the primordial germ cells during embryogenesis, suggesting that Mpvasa transcripts were maternally inherited and specifically distributed in germ cells. Taken together, these results demonstrated that Mpvasa is an applicable molecular marker for identification of gonadal and embryonic germ cells, which facilitates the isolation and utilization of germ cells in black carp.

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Explaining regional variation in home care use by demand and supply variables

Publication date: Available online 26 May 2017
Source:Health Policy
Author(s): Olivier van Noort, Fredo Schotanus, Joris van der Klundert, Jan Telgen
In the Netherlands, home care services like district nursing and personal assistance are provided by private service provider organizations and covered by private health insurance companies which bear legal responsibility for purchasing these services. To improve value for money, their procurement increasingly replaces fee-for-service payments with population based budgets. Setting appropriate population budgets requires adaptation to the legitimate needs of the population, whereas historical costs are likely to be influenced by supply factors as well, not all of which are necessarily legitimate. Our purpose is to explain home care costs in terms of demand and supply factors. This allows for adjusting historical cost patterns when setting population based budgets.Using expenses claims of 60 Dutch municipalities, we analyze eight demand variables and five supply variables with a multiple regression model to explain variance in the number of clients per inhabitant, costs per client and costs per inhabitant.Our models explain 69% of variation in the number of clients per inhabitant, 28% of costs per client and 56% of costs per inhabitant using demand factors. Moreover, we find that supply factors explain an additional 17 to 23% of variation. Predictors of higher utilization are home care organizations that are integrated with intramural nursing homes, higher competition levels among home care organizations and the availability of complementary services.



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Towards xeno-free cultures of human limbal stem cells for ocular surface reconstruction

Abstract

Isolated limbal epithelial stem cells (LESCs) were cultured with or without a 3T3 murine fibroblast feeder-layer (FL) in 4 different culture media on culture plates or on denuded human amniotic membrane (AM) support and fibrin gel support: (1) control medium supplemented with fetal bovine serum; (2) control medium supplemented with the synthetic serum "XerumFree™ XF205" (XF); (3) CnT-20 medium supplemented with "XerumFree™ XF205" (CnT-XF) and (4) CnT-20 medium supplemented with human AB serum (CnT-AB). The three xenogeneic media were compared to standard condition (control + FL) and parameters assessed included cell morphology, proliferative potential, number of passages, assessment of clonogenic and abortive colonies, life span, ∆Np63α expression and epithelial morphology on AM. During serial cultivation of LESCs, most of the tested xeno-free media supported similar numbers of cell passages, total colony number, cumulative cell doublings (CCD) rates and expression of ∆Np63α compared to control. The conditions cultivated with a FL showed a non-statistically significant higher number of cell passages and CCD rates before senescence when compared to the same conditions cultured without FL. Except for the control medium, only XF medium enabled the growth of cells on AM. The expression of ∆Np63α was comparable in all the cultures grown onto AM, when compared to the controls on fibrin gel. In conclusion, the xeno-free media enabled LESC culture both on plastic and on denuded human AM. Despite the analyses were carried out in a statistically low number of samples and need re-assessment in a larger cohort, our results suggest that the production of a completely xeno-free LESC graft could be beneficial for future clinical applications.

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Coupling between the TRPC3 ion channel and the NCX1 transporter contributed to VEGF-induced ERK1/2 activation and angiogenesis in human primary endothelial cells

Publication date: September 2017
Source:Cellular Signalling, Volume 37
Author(s): Petros Andrikopoulos, Suzanne A. Eccles, Muhammad M. Yaqoob
It has been previously demonstrated that the bi-directional transporter Na⁺/Ca²⁺ exchanger (NCX) working in the reverse (Ca²⁺-influx) - mode promotes the activation of ERK1/2 in response to the key pro-angiogenic cytokine VEGF in human endothelial cells (ECs). However, the molecular event(s) that elicit NCX reversal in VEGF-stimulated ECs remain unclear. Here we investigated whether Na⁺ influx via the diacylglycerol (DAG) – activated non-selective cation channel TRPC3 was functionally associated with NCX and whether its activity was required for VEGF-induced ERK1/2 activation and angiogenesis. We provide evidence that TRPC3 inhibitors and siRNA attenuated ERK1/2 phosphorylation, reduced PKCα activity and partially suppressed Ca²⁺ transients in response to VEGF. Additionally, TRPC3 inhibitors and siRNA significantly suppressed endothelial tubular differentiation, an in vitro indicator of angiogenesis. We also report that simulating PLCγ activation downstream of VEGF receptor 2 by application of the cell-permeable DAG analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) was sufficient to activate ERK1/2 and enhance tubular differentiation. OAG-induced ERK1/2 activation and tubulogenesis were significantly suppressed by TRPC3 and reverse-mode NCX inhibitors and siRNA. Moreover, whilst both reverse-mode NCX and TRPC3 inhibitors attenuated OAG-induced Ca²⁺ transients, only TRPC3 antagonists blunted Na⁺ influx in response to OAG. Importantly, when Na⁺ was increased in ECs by inhibiting the Na⁺-K⁺-ATPase, TRPC3 activity was dispensable for OAG-induced ERK1/2 phosphorylation. Collectively, our research suggests that DAG generation downstream of VEGF receptors activatesTRPC3 causing Na⁺ influx with subsequent reversal of NCX, ERK1/2 activation and ultimately contributes to enhanced angiogenesis. Targeting reverse-mode NCX and its upstream initiator TRPC3 could be clinically relevant in conditions characterised by abnormal VEGF signalling.



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Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia

Abstract

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100–6000 mg/m² daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032–0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587–109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset.

Prompt ultrasonography-driven combination antibiotic therapy for NEC improved survival among acute myeloid leukemia (AML) patient. Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable mortality. Vigorous antibacterial therapy, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset. This text corresponds to the final part of the abstract and it doesn't represent the legend to this figure.

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Lipid droplets accumulation and other biochemical changes induced in the fungal pathogen Ustilago maydis under nitrogen-starvation

Abstract

In many organisms, the growth under nitrogen-deprivation or a poor nitrogen source impacts on the carbon flow distribution and causes accumulation of neutral lipids, which are stored as lipid droplets (LDs). Efforts are in progress to find the mechanism of LDs synthesis and degradation, and new organisms capable of accumulating large amounts of lipids for biotechnological applications. In this context, when Ustilago maydis was cultured in the absence of a nitrogen source, there was a large accumulation of lipid bodies containing mainly triacylglycerols. The most abundant fatty acids in lipid bodies at the stationary phase were palmitic, linoleic, and oleic acids, and they were synthesized de novo by the fatty-acid synthase. In regard to the production of NADPH for the synthesis of fatty acids, the cytosolic NADP⁺-dependent isocitrate dehydrogenase and the glucose-6-phosphate and 6-phosphogluconate dehydrogenases couple showed the highest specific activities, with a lower activity of the malic enzyme. The ATP-citrate lyase activity was not detected in any of the culture conditions, which points to a different mechanism for the transfer of acetyl-CoA into the cytosol. Protein and RNA contents decreased when U. maydis was grown without a nitrogen source. Due to the significant accumulation of triacylglycerols and the particular composition of fatty acids, U. maydis can be considered an alternative model for biotechnological applications.

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Statistical shape modelling to aid surgical planning: associations between surgical parameters and head shapes following spring-assisted cranioplasty

Abstract

Purpose

Spring-assisted cranioplasty is performed to correct the long and narrow head shape of children with sagittal synostosis. Such corrective surgery involves osteotomies and the placement of spring-like distractors, which gradually expand to widen the skull until removal about 4 months later. Due to its dynamic nature, associations between surgical parameters and post-operative 3D head shape features are difficult to comprehend. The current study aimed at applying population-based statistical shape modelling to gain insight into how the choice of surgical parameters such as craniotomy size and spring positioning affects post-surgical head shape.

Methods

Twenty consecutive patients with sagittal synostosis who underwent spring-assisted cranioplasty at Great Ormond Street Hospital for Children (London, UK) were prospectively recruited. Using a nonparametric statistical modelling technique based on mathematical currents, a 3D head shape template was computed from surface head scans of sagittal patients after spring removal. Partial least squares (PLS) regression was employed to quantify and visualise trends of localised head shape changes associated with the surgical parameters recorded during spring insertion: anterior–posterior and lateral craniotomy dimensions, anterior spring position and distance between anterior and posterior springs.

Results

Bivariate correlations between surgical parameters and corresponding PLS shape vectors demonstrated that anterior–posterior (Pearson's \(r=0.64, p=0.002\) ) and lateral craniotomy dimensions (Spearman's \(\rho =0.67, p<0.001\) ), as well as the position of the anterior spring ( \(r=0.70, p<0.001\) ) and the distance between both springs ( \(r=0.67, p=0.002\) ) on average had significant effects on head shapes at the time of spring removal. Such effects were visualised on 3D models.

Conclusions

Population-based analysis of 3D post-operative medical images via computational statistical modelling tools allowed for detection of novel associations between surgical parameters and head shape features achieved following spring-assisted cranioplasty. The techniques described here could be extended to other cranio-maxillofacial procedures in order to assess post-operative outcomes and ultimately facilitate surgical decision making.

http://ift.tt/2r67EMu

Motivational Interviewing for Workers with Disabling Musculoskeletal Disorders: Results of a Cluster Randomized Control Trial

Abstract

Purpose Although functional restoration programs appear effective in assisting injured workers to return-to-work (RTW) after a work related musculoskeletal (MSK) disorder, the addition of Motivational Interviewing (MI) to these programs may result in higher RTW. Methods We conducted a cluster randomized controlled trial with claimants attending an occupational rehabilitation facility from November 17, 2014 to June 30, 2015. Six clinicians provided MI in addition to the standard functional restoration program and formed an intervention group. Six clinicians continued to provide the standard functional restoration program based on graded activity, therapeutic exercise, and workplace accommodations. Independent t tests and chi square analysis were used to compare groups. Multivariable logistic regression was used to obtain the odds ratio of claimants' confirmed RTW status at time of program discharge. Results 728 workers' compensation claimants with MSK disorders were entered into 1 of 12 therapist clusters (MI group = 367, control group = 361). Claimants were predominantly employed (72.7%), males (63.2%), with moderate levels of pain and disability (mean pain VAS = 5.0/10 and mean Pain Disability Index = 48/70). Claimants were stratified based on job attachment status. The proportion of successful RTW at program discharge was 12.1% higher for unemployed workers in the intervention group (intervention group 21.6 vs. 9.5% in control, p = 0.03) and 3.0% higher for job attached workers compared to the control group (intervention group 97.1 vs. 94.1% in control, p = 0.10). Adherence to MI was mixed, but RTW was significantly higher among MI-adherent clinicians. The odds ratio for unemployed claimants was 2.64 (0.69–10.14) and 2.50 (0.68–9.14) for employed claimants after adjusting for age, sex, pain intensity, perceived disability, and therapist cluster. Conclusion MI in addition to routine functional restoration is more effective than routine functional restoration program alone in improving RTW among workers with disabling MSK disorders.

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Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome: A group of genetic diseases characterized by a deficiency of pigment in the skin and eye, a bleeding tendency resulting from a platelet storage pool deficiency, and systemic disorders related to deficient function of lysosomes. Abbreviated HPS. Albinism that occurs in the eyes results in significant reduction in visual acuity. Pulmonary fibrosis and granulomatous colitis are known complications. The diseases are inherited as an autosomal recessive trait and are due to multiple different gene mutations. Diagnosis is made by examining blood platelets under an electron microscope or by genetic testing. There is currently no treatment for HPS. Also known as albinism with hemorrhagic diathesis, pigmented reticuloendithelial cells, and delta-storage pool disease.

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IJMS, Vol. 18, Pages 1140: Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy

Since the response to chemoradiotherapy in patients with locally advanced rectal cancer is heterogeneous, valid biomarkers are needed to monitor tumor response. Circulating microRNAs are promising candidates, however analyses of circulating microRNAs in rectal cancer are still rare. 111 patients with rectal cancer and 46 age-matched normal controls were enrolled. The expression levels of 30 microRNAs were analyzed in 17 pre-treatment patients’ plasma samples. Differentially regulated microRNAs were validated in 94 independent patients. For 52 of the 94 patients a paired comparison between pre-treatment and post-treatment samples was performed. miR-17, miR-18b, miR-20a, miR-31, and miR-193a_3p, were significantly downregulated in pre-treatment plasma samples of patients with rectal cancer (p < 0.05). miR-29c, miR-30c, and miR-195 showed a trend of differential regulation. After validation, miR-31 and miR-30c were significantly deregulated by a decrease of expression. In 52 patients expression analyses of the 8 microRNAs in matched pre-treatment and post-treatment samples showed a significant decrease for all microRNAs (p < 0.05) after treatment. Expression levels of miR-31 and miR-30c could serve as valid biomarkers if validated in a prospective study. Plasma microRNA expression levels do not necessarily represent miRNA expression levels in tumor tissue. Also, expression levels of microRNAs change during multimodal therapy.

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Review Article: Retropharyngeal Abscess—Mimickers and Masqueraders

Abstract

To discuss a case of suspected retropharyngeal abscess having important clinical and academic significance. This paper discusses an unusual presentation and evolution of a well known condition such as retropharyngeal abscess. Though the diagnosis in this case was initially a retropharyngeal abscess, several unusual findings were evident, which interfered with the optimal management of the patient. A literature review revealed rare causes and lesions mimicking a retropharyngeal abscess, such as retropharyngeal calcific tendinitis and Kawasaki disease, which are neither familiar to otolaryngologists nor other specialists such as orthopedicians. It is possible that this patient was both over treated and undertreated at the same time. Though the diagnosis in this case could not be established with certainty, several important pieces of information came up, especially unusual causes of retropharyngeal abscess and management of the same. Retropharyngeal abscess is a well-known condition with established modes of management. However, certain variations may occur and may pose challenges in diagnosis and management. These variations are little known and need to be highlighted so that optimal management is ensured.

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Invasive Fungal Infection in Acute Myeloid Leukemia Associated with Myeloid Sarcoma of the Sinonasal Cavity: A Rare Case

Abstract

Myeloid sarcoma is a rare malignant extramedullary neoplasm of myeloid precursor cells. The majority of these cases occur in patients with known leukemia or those who eventually develop the disease. It can occur in various sites but sinonasal cavity involvement along with invasive fungal infection is exceedingly rare.

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Dendritic cells combined with tumor cells and α-galactosylceramide induce a potent, therapeutic and NK-cell dependent antitumor immunity in B cell lymphoma

Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells pla...

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Deformation induced loss of ellipticity in an anisotropic circular cylindrical tube

Abstract

When a transversely isotropic circular cylindrical tube is subject to axial extension and inflation, the governing equations of equilibrium can lose ellipticity under certain combinations of deformation and direction of transverse isotropy. In this paper, it is shown how the inclusion of an axial shear deformation moderates the loss of ellipticity condition. In particular, this condition is analysed for a material model consisting of an isotropic neo-Hookean matrix within which are embedded fibres whose properties are characterized by the addition to the strain-energy function of a reinforcing model depending on the local fibre direction.

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On the relationship between the stochastic Galerkin method and the pseudo-spectral collocation method for linear differential algebraic equations

Abstract

Polynomial chaos-based methods have been extensively applied in electrical and other engineering problems for the stochastic simulation of systems with uncertain parameters. Most of the implementations are based on either the intrusive stochastic Galerkin method or on non-intrusive collocation approaches, of which a very common example is the pseudo-spectral method based on Gaussian quadrature rules. This paper shows that, for the important class of linear differential algebraic equations, the latter can be cast as an approximate factorization of the stochastic Galerkin approach, thus generalizing recent discussions in literature in this regard. Consistently with this literature, we show that the factorization turns out to be exact for first-order random inputs, and hence the two methods coincide under this assumption. Further, the presented results also generalize recent work in the field of electrical circuit simulation, in which a similar decomposition was derived ad hoc, via error minimization, for the case of Hermite chaos. We demonstrate that the factorization stems from the general properties of orthogonal polynomials and the error introduced by the approximation—or in other terms, the error of the stochastic collocation method in comparison with the stochastic Galerkin method—is carefully quantified and assessed. An illustrative example concerning the stochastic analysis of an RLC circuit is used to illustrate the main findings of this paper. In addition, a more complex and real-life example allows emphasizing the generality of the achieved results.

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Phase I study of glasdegib (PF-04449913), an oral smoothened inhibitor, in Japanese patients with select hematologic malignancies

Summary

The hedgehog signaling pathway regulates multiple morphogenetic processes during embryogenesis. Aberrant activation of the hedgehog pathway signal transduction in adult tissues is associated with the pathogenesis of hematologic malignancies and solid tumors. We report findings from an open-label, multicenter phase I trial of the selective, small-molecule hedgehog signaling inhibitor glasdegib (PF-04449913) in Japanese patients with select advanced hematologic malignancies. Glasdegib was administered as once-daily oral doses (25, 50, and 100 mg) in 28-day cycles after a lead-in dose on Day –5. The primary objectives were to determine first-cycle dose-limiting toxicities, safety, vital signs, and laboratory test abnormalities. Secondary objectives included evaluation of pharmacokinetics, pharmacodynamics, and preliminary evidence of clinical activity of glasdegib. No dose-limiting toxicities were noted in the 13 patients in this study. All patients experienced at least one treatment-emergent, all-causality adverse event. The most frequent treatment-related adverse events (observed in ≥3 patients) were dysgeusia (n=9), muscle spasms (n=5), alopecia, decreased appetite (n=4 each), and increased blood creatinine phosphokinase, constipation, and diarrhea (n=3 each). Two deaths occurred during the study and were deemed not to be treatment-related due to disease progression. Glasdegib demonstrated dose-proportional pharmacokinetics, marked downregulation of the glioma-associated transcriptional regulator GLI1 expression in normal skin, and evidence of preliminary clinical activity, although data are limited. Glasdegib was safe and well tolerated across the dose levels tested. It is confirmed that the 100-mg dose is safe and tolerable in Japanese patients, and this dose level will be examined in the future clinical trial.

This article is protected by copyright. All rights reserved.

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The Perception of Formant Tuning in Soprano Voices

At the upper end of the soprano range, singers adjust their vocal tract to bring one or more of its resonances (Rn) toward a source harmonic, increasing the amplitude of the sound; this process is known as resonance tuning. This study investigated the perception of (R1) and (R2) tuning, key strategies observed in classically trained soprano voices, which were expected to be preferred by listeners. Furthermore, different vowels were compared, whereas previous investigations have usually focused on a single vowel.

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Contact Quotient of Female Singers Singing Four Pitches for Five Vowels in Normal and Pressed Phonations

The present study aimed to investigate the contact quotient (CQ) values of breathy, normal, and pressed phonation types in four different sections of the female singing range.

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Gene Set Enrichment Analyses: lessons learned from the heart failure phenotype

Genetic studies for complex diseases have predominantly discovered main effects at individual loci, but have not focused on genomic and environmental contexts important for a phenotype. Gene Set Enrichment Ana...

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Giovanni Verga (1879–1923), author of a pioneering treatise on pituitary surgery: the foundations of this new field in Europe in the early 1900s

Abstract

The field of pituitary surgery was born in the first decade of the twentieth century in Europe, and it evolved rapidly with the development of numerous innovative surgical techniques by some of the founding fathers of neurosurgery. This study investigates the pioneering Italian treatise on pituitary surgery, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), published in 1911 by Giovanni Verga (1879–1923), a surgeon from Pavía and one of Golgi's disciples. This little-known monograph compiles the earliest experience on pituitary surgery through the analysis of the first 50 procedures performed between 1903 and 1911. We conducted a biographical survey of Giovanni Verga and the motivations for his work on pituitary surgery. In addition, a systematic analysis of all original reports and historical documents about these pituitary procedures referenced in Verga's treatise was carried out. Verga's treatise provides a summary of the techniques employed and surgical outcomes for the first 50 attempted procedures of pituitary tumor removal. This monograph is the only scientific source that includes a complete account of the series of 10 pituitary tumors operated on by Sir Victor Horsley in the 1900s. Three major types of surgery were employed: (i) palliative procedures of craniectomy (n = 6); (ii) transcranial approaches to the pituitary gland, either subfrontal or subtemporal (n = 13); and (iii) transphenoidal routes to expose the sella turcica, either using an upper transnasal-transethmoidal approach (n = 19) or a lower sublabial/endonasal-transeptal one (n = 12). An operative mortality rate of 36% (n = 17) was observed in these early series. The pathological nature of the tumors operated on was available in 42 cases. There were 28 adenomas and 15 craniopharyngiomas. Sir Victor Horsley (1857–1916) and the Viennese surgeons Anton von Eiselsberg (1860–1939) and Oskar Hirsch (1877–1965) were the leading European figures in the development of pituitary surgery. Giovanni Verga's treatise La Patologia Chirurgica dell'Ipofisi is a fundamental, pioneering book in the history of pituitary surgery, a work that compiles the foundations of this field in Europe and the only authoritative source providing a complete record of pituitary procedures performed by Sir Victor Horsley.

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Clinical implications of c-maf expression in plasma cells from patients with multiple myeloma

Abstract

Background

Multiple myeloma (MM) is a type of hematological malignancy with significant heterogeneity in clinical features and prognosis. Cytogenetic abnormalities are the major factors affecting patient outcomes. Studies have shown that immunohistochemistry (IHC)-based detection of cancer-related genes expression could be alternative indicators for the prognosis of MM.

Methods

Nuclear expression of c-maf protein in the bone marrow plasma cells of 128 multiple myeloma patients were examined by IHC, and its association with the clinicopathological features of MM patients was analyzed as well.

Results

Among the 128 patients, the positive rate of c-maf protein expression was up to 30.5%, which had no correlation with patient age, M protein type, Durie-Salmon staging system, the International Staging System, abnormal plasma cell ratio in the bone marrow, or the level of peripheral blood hemoglobin, serum calcium or lactate dehydrogenase. However, the c-maf-positive patients had a significantly higher rate of hypoproteinemia (p = 0.026) and higher serum β2-microglobulin levels (>2500 μg/L) (p = 0.007). Patients with negative c-maf expression had higher remission rates upon the treatment of non-bortezomib-based regimens although no effect of c-maf expression on progression-free survival or overall survival was observed.

Conclusion

Patients with negative c-maf expression had higher remission rates upon the treatment of non-bortezomib-based regimens although no effect of c-maf expression on survival was observed. A further large-scale prospective study is required to verify these findings.

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PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease [Research]

Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function. In cultured podocytes, PACSIN2 and nephrin colocalize and interact. We show that nephrin is endocytosed in PACSIN2-positive membrane regions and that PACSIN2 overexpression increases both nephrin endocytosis and recycling. We identify rabenosyn-5, which is involved in early endosome maturation and endosomal sorting, as a novel interaction partner of PACSIN2. Interestingly, rabenosyn-5 expression is increased in podocytes in obese ZDF rats, and, in vitro, its overexpression enhances the association of PACSIN2 and nephrin. We also show that palmitate, which is elevated in diabetes, enhances this association. Collectively, PACSIN2 is up-regulated and nephrin is abnormally localized in podocytes of diabetic ZDF rats. In vitro, PACSIN2 enhances nephrin turnover apparently via a mechanism involving rabenosyn-5. The data suggest that elevated PACSIN2 expression accelerates nephrin trafficking and associates with albuminuria.—Dumont, V., Tolvanen, T. A., Kuusela, S., Wang, H., Nyman, T. A., Lindfors, S., Tienari, J., Nisen, H., Suetsugu, S., Plomann, M., Kawachi, H., Lehtonen, S. PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease.

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Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey

Abstract

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.

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Antibodies against linear epitopes on Goodpasture autoantigen in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract

In a substantial number of patients with crescentic glomerulonephritis, both anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) are detected simultaneously. ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the antibodies against linear epitopes on Goodpasture autoantigen in sera from patients with ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of autoantibodies. Thirty-one patients with ANCA-associated vasculitis were enrolled in this study. Twenty-four overlapping linear peptides were synthesized across the whole sequence of Goodpasture autoantigen. Serum antibodies against linear peptides were detected by ELISA and their associations with clinical features were further analyzed. Twenty-five out of the thirty-one (80.6%) sera from patients with ANCA-associated vasculitis possessed antibodies against linear peptides on Goodpasture autoantigen. These antibodies could be detected in 50% of patients with normal renal function (Scr ≤ 133 μmol/L), 70% of patients with moderate renal dysfunction (133 μmol/L < Scr ≤ 600 μmol/L), and 94% of patients with renal failure (Scr > 600 μmol/L) (P = 0.032). The highest recognition frequencies were found for peptides P4 (51.6%), P14 (54.8%), and P24 (54.8%), which contained the sequences that constitute the conformational epitopes of E_A (P4) and E_B (P14) recognized by anti-GBM antibodies. The level of anti-P4 antibodies was positively correlated with the percentage of crescents in glomeruli (r = 0.764, P = 0.027). Patients with anti-P24 antibodies had a significantly higher prevalence of renal dysfunction on diagnosis (88.2 vs. 42.9%, P = 0.018). Antibodies against linear epitopes on Goodpasture autoantigen could be detected in sera of patients with ANCA-associated vasculitis, which might mediate the production of antibodies towards the conformational epitopes on Goodpasture autoantigen, namely, the anti-GBM antibodies.

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Distant skeletal muscle metastasis to sternocleidomastoid in the setting of recurrent papillary thyroid carcinoma

Nitish Virmani, Jyoti Dabholkar

Thyroid Research and Practice 2017 14(2):77-80

Papillary thyroid carcinoma (PTC), the most common form of differentiated thyroid cancer, is characterized by an indolent course and excellent prognosis. Although its spread to regional lymph nodes is well known, distant metastases are seen only in a minority of patients with lungs being the most common site. Skeletal muscle metastases are extremely rare even in follicular thyroid carcinoma, in which hematogenous spread is known to occur. We describe a case of skeletal muscle metastasis to sternocleidomastoid muscle in a case of PTC in the setting of local recurrence.

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Clinical approach to congenital hypothyroidism

Sunetra Mondal, Pradip Mukhopadhyay, Sujoy Ghosh

Thyroid Research and Practice 2017 14(2):45-53

Congenital hypothyroidism (CH) is a preventable cause of mental retardation. The principal causes include thyroid dysgenesis and dyshormonogenesis. Central CH is rare. Due to absence of overt symptoms at birth, diagnosis is often delayed. There are some known syndromic associations with extrathyroidal anomalies. Neonatal screening programs help in early detection and categorization of cases requiring immediate treatment or close follow-up. Results of screening tests could guide further tests required for confirmation diagnosis and urgency of replacement therapy. A diagnostic protocol starting with an ultrasonography of thyroid and serum thyroglobulin levels can aid identify the probable underlying etiology and dictate the cases requiring scintigraphy or genetic tests. Early initiation of treatment with oral levothyroxine improves neurocognitive outcomes. Some cases might have transient hypothyroidism and reevaluation at 3 years of age may help in further discontinuation of treatment.

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The kidney and the thyroid – Together in function and disease

Krishna G Seshadri

Thyroid Research and Practice 2017 14(2):43-44



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National health programs related to thyroid

Kanica Kaushal, Sanjay Kalra

Thyroid Research and Practice 2017 14(2):54-57

Identification of health objectives is one of the more visible strategies to direct the activities of the health sector. The government of India and its nodal ministry – Ministry of Health and Family Welfare undoubtedly has the central and primary role in the implementation of the health program. In this article, the authors have tried to review the available national programs for prevention and treatment of thyroid diseases; National Newborn Screening Programme including congenital hypothyroidism, Rashtriya Bal Swasthya Karyakram, National Guidelines for Screening of Hypothyroidism during Pregnancy, National Iodine Deficiency Disorders Control Programme and National Family Health Survey 3 and 4.

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A rare presentation of autoimmune thyroid disease in mother and neonate postpartum

Mythili Ayyagari

Thyroid Research and Practice 2017 14(2):86-88

This is a case of long-standing hypothyroidism on levothyroxine (LT4) replacement developing Graves' disease postpartum and the newborn presenting with transient congenital hypothyroidism. The clinical and laboratory data of the case are reported along with a brief literature review. A 27-year-old female who has hypothyroidism for the past 3 years and gestational diabetes mellitus delivered uneventfully. The thyroid function tests (TFTs) of the newborn showed congenital hypothyroidism which was transient and resolved by 3 months' age. An ultrasound of thyroid showed gland in situ. The diagnosis of the newborn is transient congenital hypothyroidism probably due to thyroid-stimulating hormone receptor-blocking antibodies (TBAbs). The mother who has hypothyroidism for the past 3 years was stable with euthyroidism and was on LT4 100 ug daily. Seven months postpartum, she had lid lag and proptosis of her left eye. Her TFTs revealed thyrotoxicosis and was advised to stop LT4. Magnetic resonance imaging orbits were normal and her TBAbs are elevated at 4.65 IU/L (<1.22). Antimicrosomal antibodies and antithyroid peroxidase antibodies were negative. The orbitopathy resolved over 6 weeks and the mother remains euthyroid without LT4 on a follow-up period of 8 months. Close monitoring of autoimmune thyroid disease (AITD) in pregnancy and postpartum is necessary due to the immune switching in this period and may obviate the need for LT4 therapy. The suspicion of transient congenital hypothyroidism due to TBAb should be high in neonates born to mothers with AITD.

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Thyroid dysfunction in critically ill patients in a tertiary care hospital in Sikkim, India

M Suresh, Nitin K Srivastava, Amit Kumar Jain, Parvati Nandy

Thyroid Research and Practice 2017 14(2):58-62

Background: During critical illness, patients with no history of thyroid disorders may experience multiple changes in their thyroid hormone levels. Such changes are termed as euthyroid sick syndrome. The extent of change correlates with the severity of the illness and its outcomes in critically ill patients. Objectives: The aim of this study was to identify critically ill patients and grade them clinically according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) severity scale and evaluate the thyroid function tests (TFTs) and to document the outcome and relate the APACHE II severity scale with TFTs. Methods: A descriptive, observational hospital-based study was conducted on critically ill patients admitted to the Intensive Care Unit who fulfilled the inclusion criteria. All data were entered into Microsoft Excel sheet and were analyzed using GraphPad InStat software. Results: The majority of the patients belonged to geriatric age group (49%) and were male (55%). Cardiovascular diseases (43%) constituted the major morbidity. The majority had APACHE II score ≥20 (71%) and succumbed (45%) to their illness within 10 days. The majority of them had a low total triiodothyronine (T3) (49%), and there was a significant inverse correlation (P = 0.0235) between severity of illness and low serum total T3 levels whereas there was no relationship between total thyroxine or thyroid-stimulating hormone levels and severity of illness. Conclusions: Serum T3 has a significant inverse relationship to the severity of critically ill patients.

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Transoral thyroidectomy, vestibular approach using two ports: A novel technique

Vivek Aggarwal, Raja Bhanu Kiran, Monika Garg, Deepak Khandelwal

Thyroid Research and Practice 2017 14(2):75-76

Cosmesis is a prime concern for many patients undergoing thyroid surgery. Postthyroidectomy scar-related apprehension among patients has forced the surgeons to develop techniques to reduce the scar or even without scar. We report a case of a young female with thyroid nodule who underwent transoral endoscopic thyroidectomy done through a novel technique (transoral vestibular approach using two ports) at our center as potentially scarless thyroid surgery.

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Prevalence of hypothyroidism in Assam: A clinic-based observational study

Anindita Mahanta, Sushmita Choudhury, Sarojini Dutta Choudhury

Thyroid Research and Practice 2017 14(2):63-70

Introduction: Hypothyroidism is a common functional disorder of the thyroid gland. Despite extensive research, data on this subject are lacking from the northeastern part of India, which falls in the Sub-Himalayan goitrogenic belt. Therefore, we decided to study the profile of hypothyroidism in Assam, a northeastern state with the following objectives: to determine the prevalence of hypothyroidism and to describe the various modes of clinical presentation. Materials and Methods: The study was conducted at a clinic-cum-radioimmunoassay laboratory in Guwahati, Assam, from January to November 2011. Two thousand and four hundred fifty-six patients referred to our center from different parts of Assam were evaluated clinically and their thyroid profile was estimated. Antithyroid peroxidase (TPO) antibody was estimated in 1950 patients. Results: The prevalence of overt hypothyroidism was 10.9% (n = 267) and that of subclinical hypothyroidism was 13.1% (n = 321). Male:female ratio was 1:3. Among the cases of overt hypothyroidism, 247 (92.51%) were adult hypothyroids, 15 (5.62%) juvenile hypothyroids, and 5 (1.87%) cretins. The common presenting features of hypothyroidism were weakness (98%), lethargy (95%), dry and coarse skin (87%), and body ache (85%). Uncommon modes of presentation were pleural and pericardial effusion, low body weight, frequent motions, and palpitations. Postthyroidectomy and drug-induced hypothyroidism accounted for 2.38% cases each and postpartum hypothyroidism for 3.74% cases. Thirteen percent cases presented with goiter. The prevalence of anti-TPO antibody in the study population was 8.41%. Conclusion: Hypothyroidsm is no longer a rarity, and Assam is no exception to this phenomenon. A population-based epidemiological study of thyroid disorders in Northeast India is an urgent need.

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Primary hypothyroidism presenting as a pituitary macroadenoma and precocious puberty

Balram Sharma, Hema Singh, Sanjay Saran, Sandeep Kumar Mathur

Thyroid Research and Practice 2017 14(2):81-85

The association in young females of long-standing primary hypothyroidism, isosexual precocious pseudopuberty, and multicystic enlarged ovaries was first described in 1960 by Van Wyk and Grumbach. In this case study, we report a girl with precocious puberty, poor linear growth, decreased vision, and a large pituitary pseudotumor due to long-standing hypothyroidism with regression of all components following thyroxine (T4) supplementation. This girl aged 12 years and 3 months presented in Endocrinology Department with complaints of early menarche starting at the age of 8 years with normal cycles along with early progressive breast development starting almost simultaneously. On examination, she had a reduced growth for age (<5th centile) with adequate breast development (Tanner Stage 3) but no pubic or axillary hair development. Physical and biochemical examination for blood indices revealed a microcytic hypochromic anemia. Most importantly, she had an elevated thyroid stimulating hormone >150 μIU/ml (0.35–5.5) and a free T4 (FT4) and free triiodothyronine below normal limits suggestive of primary hypothyroidism. Furthermore, serum prolactin levels were elevated along with an elevated serum follicle-stimulating hormone, luteinizing hormone, and estradiol. Multicystic ovaries and a bulky uterus on ultrasound were suggestive of precocious puberty. Magnetic resonance imaging scan of the sella turcica was suggestive of a pituitary macroadenoma. Posttreatment with gluten-free diet, iron supplements, and T4 replacement, her thyroid function, hemoglobin, and prolactin normalized along with a regression in the size of the ovary. Therefore, in patients of this age presenting with a pituitary macroadenoma, anemia, precocious puberty, and primary hypothyroidism, medical management was preferred over neurosurgical intervention so as to avoid permanent hypopituitarism and lifelong hormone replacement therapy.

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Clinicopathologic profile of glomerular diseases associated with autoimmune thyroiditis

Kunal Gandhi, Karamvir Godara, Dhananjai Agrawal, Vinay Malhotra, Pankaj Beniwal, Amith Dsouza

Thyroid Research and Practice 2017 14(2):71-74

Introduction: Thyroid hormones are known to influence renal function, development, and renal hemodynamics. In this study, we aimed to de ne the frequency and characteristics of various glomerular diseases associated with autoimmune thyroiditis. Methods: We reviewed retrospectively 36 patients with autoimmune thyroiditis referred for evaluation of proteinuria, hematuria, and/or renal impairment. Renal biopsy was performed in 32 patients and was examined with light microscopy and immunofluorescence. Six months follow-up data of 22 patients was reviewed. Results: The mean age of study population was 43.6 years. Most of them were females (n = 28). Mean duration of hypothyroidism (HT) was 1.5 years. Hypertension was seen in 16 patients and deranged renal function (estimated glomerular filtration rate <60 ml/min/1.73 m2) in 18 with a mean serum creatinine of 1.28 mg/dl at time of biopsy. 10 patients presented with nephrotic syndrome, 33 presented with isolated proteinuria and 22 presented with hematuria with or without significant proteinuria The most common histopathologic finding was membranous nephropathy (MGN) (n = 16), followed by minimal-change nephropathy (n = 5), focal segmental glomerulosclerosis (n = 5), immunoglobulin A nephropathy (n = 3), amyloidosis (n = 2), and membranoproliferative glomerulonephritis (n = 1). Membranous nephropathy was the most common finding inn patients with the nephrotic syndrome. Conclusion: Glomerular pathologies associated with HT are diverse and similar to those found in the general population; therefore, renal biopsy should be performed in cases with progressive renal failure or urinary abnormalities.

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Hashimoto's encephalopathy in a 10-year-old girl

V Shobi Anandi, Shaila Bhattacharyya, Bidisha Banerjee

Thyroid Research and Practice 2017 14(2):89-91

Hashimoto's encephalopathy (HE) is a rare but probably an unrecognized and underdiagnosed condition in children. Early diagnosis is critical since these patients respond dramatically to corticosteroid therapy. The diagnosis of HE requires a strong clinical suspicion along with a triad of positive antithyroid antibodies, encephalopathy not explained by another etiology, and a response to corticosteroids. We report the case of a 10-year-old female child with HE and review the literature.

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Enhanced Afterglow Performance of Persistent Luminescence Implants for Efficient Repeatable Photodynamic Therapy

ACS Nano

DOI: 10.1021/acsnano.7b01505

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Experimental and Theoretical Investigations of Surface-Assisted Graphene Nanoribbon Synthesis Featuring Carbon–Fluorine Bond Cleavage

ACS Nano

DOI: 10.1021/acsnano.7b02316

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The iron-dependent mitochondrial superoxide dismutase SODA promotes Leishmania virulence [Molecular Bases of Disease]

Leishmaniasis is one of the leading global neglected diseases, affecting millions of people worldwide. Leishmania infection depends on the ability of insect-transmitted metacyclic promastigotes to invade mammalian hosts, differentiate into amastigotes and replicate inside macrophages. To counter the hostile oxidative environment inside macrophages, these protozoans contain anti-oxidant systems that include iron-dependent superoxide dismutases (SODs) in mitochondria and glycosomes. Increasing evidence suggests that in addition to this protective role, Leishmania mitochondrial SOD may also initiate H2O2-mediated redox signaling that regulates gene expression and metabolic changes associated with differentiation into virulent forms. To investigate this hypothesis, we examined the specific role of SODA, the mitochondrial SOD isoform in Leishmania amazonensis. Our inability to generate L. amazonensis SODA null mutants and the lethal phenotype observed following RNAi-mediated silencing of the T. brucei SODA ortholog suggests that SODA is essential for trypanosomatid survival. L. amazonensis metacyclic promastigotes lacking one SODA allele failed to replicate in macrophages and were severely attenuated in their ability to generate cutaneous lesions in mice. Reduced expression of SODA also resulted in mitochondrial oxidative damage and failure of SODA/∆sodA promastigotes to differentiate into axenic amastigotes. SODA expression above a critical threshold was also required for the development of metacyclic promastigotes, as SODA/∆sodA cultures were strongly depleted in this infective form and more susceptible to reactive oxygen species (ROS)-induced stress. Collectively, our data suggests that SODA promotes Leishmania virulence by protecting the parasites against mitochondria-generated oxidative stress and by initiating ROS mediated signaling mechanisms required for the differentiation of infective forms.

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Knockdown of Sodium-Calcium Exchanger 1 Induces Epithelial to Mesenchymal Transition in Kidney Epithelial Cells [Cell Biology]

Mesenchymal to epithelial transition (MET) and epithelial to mesenchymal transition (EMT) are important processes in kidney development. Failure to undergo MET during development leads to the initiation of Wilms tumor (WT) whereas EMT contributes to the development of renal cell carcinomas (RCC). The role of calcium regulators in governing these processes is becoming evident. We demonstrated earlier that Na+/Ca2+ exchanger 1 (NCX1), a major calcium exporter in renal epithelial cells, regulates epithelial cell motility. Here, we show for the first time that NCX1 mRNA and protein expression was downregulated in WT and RCC. Knockdown of NCX1 in MDCK cells induced fibroblastic morphology, increased inter-cellular junctional distance, induced paracellular permeability, loss of apico-basal polarity in three-dimensional cultures, and anchorage independent growth, accompanied by expression of mesenchymal markers. We also provide evidence that NCX1 interacts with and anchors E-cadherin to the cell surface independent of NCX1 ion transport activity. Consistent with destabilization of E-cadherin, NCX1 knockdown cells showed an increase in β-catenin nuclear localization, enhanced transcriptional activity and upregulation of downstream targets of β-catenin signaling pathway. Taken together, knockdown of NCX1 in MDCK cells alters epithelial morphology and characteristics by destabilization of E-cadherin and induction of β-catenin signaling.

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The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients

Abstract

Purpose

The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients.

Methods

A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 − 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays.

Results

The patients with variant genotypes of VKORC1 − 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 − 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability.

Conclusions

VKORC1 − 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

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Open-access genetic screening for hereditary breast cancer is feasible and effective

Ashkenazi Jewish women are known to have a predisposition to the inherited breast cancers BRCA1 and BRCA2, but currently genetic testing in this group is limited to women affected by breast and ovarian cancers and those who are unaffected but have a...

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Fully Stretchable Optoelectronic Sensors Based on Colloidal Quantum Dots for Sensing Photoplethysmographic Signals

ACS Nano

DOI: 10.1021/acsnano.7b01894

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Vehicle classification for large-scale traffic surveillance videos using Convolutional Neural Networks

Abstract

Vehicle classification plays an important role in intelligent transport system. However, because the conventional vehicle classification methods are not robust to variations such as illumination, weather, noise, and the classification accuracy cannot meet the requirements of practical applications. Therefore, a new vehicle classification method using Convolutional Neural Networks is proposed in this paper, which consists of two steps: pre-training and fine-tuning. In pre-training, GoogLeNet is pre-trained on ILSVRC-2012 dataset to obtain the initial model with the corresponding connection weights. In fine-tuning, the initial model is further fine-tuned on VehicleDataset which is constructed with 13,700 images in this paper to obtain the final classification model. All images in the VehicleDataset are extracted from real highway surveillance videos, including variations of illumination, noise, resolution, angle of video cameras and weather. The vehicles are divided into six categories, i.e., bus, car, motorcycle, minibus, truck and van. The performance evaluation is carried out on the VehicleDataset. The experimental results show that the proposed method can avoid the complicated process of manually extracting features and the average classification accuracy is up to 98.26%, which is 3.42% higher than the conventional methods using "Feature + Classifier".

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TH1 phenotype of T follicular helper cells indicates an IFNγ-associated immune dysregulation in CD21low CVID patients

A subgroup of patients with Common Variable Immunodeficiency (CVID) suffers from immune dysregulation, manifesting as autoimmunity, lymphoproliferation and organ inflammation, and thereby increasing morbidity and mortality. Therefore, treatment of these complications demands a deeper comprehension of their etiology and pathophysiology.

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Utility of intraoperative and postoperative radiographs in pediatric cochlear implant surgery

Routine plain film radiographs are often obtained to confirm proper placement of electrode after pediatric cochlear implant surgery. Objective is to evaluate necessity of routine radiographs in pediatric cochlear implant cases.

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RT @ESSOnews : Interesting @ecancer free seminar on #prostatecancer live from #ASCO17 for healthcare professionals https://t.co/qnABQSj7lC h…

RT @ESSOnews : Interesting @ecancer free seminar on #prostatecancer live from #ASCO17 for healthcare professionals https://t.co/qnABQSj7lC h…

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Title Page/Section Editors

Publication date: August 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 8





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Change in Excitability of Cortical Projection After Modified Catheter Balloon Dilatation Therapy in Brainstem Stroke Patients with Dysphagia: A Prospective Controlled Study

Abstract

Although the modified balloon dilatation therapy has been demonstrated to improve pharyngeal swallowing function post stroke, the underlying neural mechanisms of improvement are unknown. Our aims are (1) to investigate the effect of modified balloon dilatation on the excitability of corticobulbar projections to the submental muscle in dysphagic patients with brainstem stroke and (2) the relation between changes in excitability and pharyngeal kinematic modifications. Thirty patients with upper esophageal sphincter (UES) dysfunction due to unilateral brainstem stroke were recruited into two groups. The patients in dilatation group received modified balloon dilatation and conventional therapies, and those in control were only treated by conventional therapies (twice per day). The amplitudes of bilateral submental motor evoked potentials (MEPs) induced by transcranial magnetic stimulations over bilateral motor cortex, diameters of UES opening (UOD) and maximal displacement of hyoid (HD) were all assessed at baseline and the endpoint of treatments. Repeated ANOVA analysis revealed significant main effect of group, time and MEP laterality on MEP amplitudes (p = 0.02). There were no differences in the pretreatment measures between groups (all p > 0.05). After treatment, the amplitudes of affected submental MEP evoked by ipsilateral cortical pulse as well as UOD and HD were significantly different in dilatation group compared to control (amplitude: p = 0.02, UOD: p < 0.001, HD: p = 0.03). The differences of pre- and post-treatment amplitudes of the affected MEP evoked by ipsilateral stimulation showed a positive correlation with the improvement of HD (dilatation: R ² = 0.51, p = 0.03; control: R ² = 0.39, p = 0.01), rather than UOD in both groups (all p > 0.05). In conclusion, modified balloon dilatation therapy can increase the excitability of affected projection in patients with unilateral brainstem stroke.

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Projective biomechanical depth matching for soft tissue registration in laparoscopic surgery

Abstract

Purpose

A key component of computer- assisted surgery systems is the accurate and robust registration of preoperative planning data with intraoperative sensor data. In laparoscopic surgery, this image-based registration remains challenging due to soft tissue deformations. This paper presents a novel approach for biomechanical soft tissue registration of preoperative CT data with stereo endoscopic image data.

Methods

The proposed method consists of two registrations steps. First, we use a 3D surface mosaic from partial surfaces reconstructed from stereo endoscopic images to initially align the biomechanical model with the intraoperative position and shape of the organ. After this initialization, the biomechanical model is projected onto newly captured surfaces, resulting in displacement boundary conditions, which in turn are used to update the biomechanical model.

Results

The method is evaluated in silico, using a human liver model, and in vivo, using porcine data. The quantitative in silico data shows a stable behaviour of the biomechanical model and root-mean-square deviation of volume vertices of under 3 mm with adjusted biomechanical parameters.

Conclusion

This work contributes a fully automatic featureless non-rigid registration approach. The results of the in silico and in vivo experiments suggest that our method is able to handle dynamic deformations during surgery. Additional experiments, especially regarding human tissue behaviour, are an important next step towards clinical applications.

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Endoscopic video-assisted transoral resection of lateral oropharyngeal tumors

Abstract

Endoscopic, video-assisted transoral resection of oropharyngeal tumors is a novel technique carried out using common instruments present in most otolaryngology departments. The technique facilitates oropharyngeal resection akin to transoral robotic surgery (TORS) without the need for a robot.

A dual surgeon approach, analogous to that of endoscopic skull base surgery is used. Each surgeon can actively participate in the resection with several key advantages over current techniques. The technique is applicable to departments internationally especially where the use of a robot is prohibited by cost or availability. This is especially important given the resection of oropharyngeal tumours offers the opportunity of single modality treatment or reduced intensity adjuvant treatment compared to traditional non-surgical therapy.

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How many have you done, doctor? When is enough enough?

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2102Ep embryonal carcinoma cells have compromised respiration and shifted bioenergetic profile distinct from H9 human embryonic stem cells

Publication date: Available online 26 May 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Lyudmila Ounpuu, Aleksandr Klepinin, Martin Pook, Indrek Teino, Nadezda Peet, Kalju Paju, Kersti Tepp, Vladimir Chekulayev, Igor Shevchuk, Sulev Koks, Toivo Maimets, Tuuli Kaambre
Recent studies have shown that cellular bioenergetics may be involved in stem cell differentiation. Considering that during cancerogenesis cells acquire numerous properties of stem cells, it is possible to assume that the energy metabolism in tumorigenic cells might be differently regulated. The aim of this study was to compare the mitochondrial bioenergetic profile of normal pluripotent human embryonic stem cells (hESC) and relatively nullipotent embryonal carcinoma cells (2102Ep cell line).We examined three parameters related to cellular bioenergetics: phosphotransfer system, aerobic glycolysis, and oxygen consumption. Activities and expression levels of main enzymes that facilitate energy transfer were measured. The oxygen consumption rate studies were performed to investigate the respiratory capacity of cells.2102Ep cells showed a shift in energy distribution towards adenylate kinase network. The total AK activity was almost 3 times higher in 2102Ep cells compared to hESCs (179.85±5.73 vs 64.39±2.55mU/mg of protein) and the expression of AK2 was significantly higher in these cells, while CK was downregulated. 2102Ep cells displayed reduced levels of oxygen consumption and increased levels of aerobic glycolysis compared to hESCs. The compromised respiration of 2102Ep cells is not the result of increased mitochondrial mass, increased proton leak, and reduced respiratory reserve capacity of the cells or impairment of respiratory chain complexes. Our data showed that the bioenergetic profile of 2102Ep cells clearly distinguishes them from normal hESCs. This should be considered when this cell line is used as a reference, and highlight the importance of further research concerning energy metabolism of stem cells.

Graphical abstract

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European Society of Neuroradiology (ESNR)

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Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis

Abstract

Purpose

Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments.

Methods

Literature was searched in several electronic databases, and study selection was based on précised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients.

Results

Thirty-three studies (1121 schizophrenia patients; age 32.66 years [95% confidence interval (CI) 30.19, 35.13]; 65.95 % [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] −0.23 [−0.14, −0.32]; p ˂ 0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score −0.30 [−0.23, −0.36]; p ˂ 0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p = 0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p = 0.00001).

Conclusion

Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients.

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Differential diagnosis of oligodendroglial and astrocytic tumors using imaging results: the added value of perfusion MR imaging

Abstract

Purpose

The purposes of the present study are to assess whether different characteristics of oligodendrogliomas and astrocytic tumors are visible on MR imaging and to determine the added value of perfusion imaging in conventional MR imaging when differentiating oligodendrogliomas from astrocytic tumors.

Methods

We retrospectively studied 22 oligodendroglioma and 54 astrocytic tumor patients, including glioblastoma multiforme (GBM). The morphological tumor characteristics were evaluated using MR imaging. The rCBV, K ^trans, and V _e values were recorded. All imaging and clinical values were compared. The ability to discriminate between the two entities was evaluated using receiver operating characteristic curve analyses. Separate comparison analysis between oligodendroglioma and astrocytic tumors excluding GBM was also performed.

Results

The presence of calcification, higher cortex involvement ratio, and lower V _e value were more representative of oligodendrogliomas than astrocytic tumors (P = <0.001, 0.038, and <0.001, respectively). The area under the curve (AUC) value of a combination of calcification and cortex involvement ratio was 0.796. The combination of all three parameters, including V _e, further increased the diagnostic performance (AUC = 0.881). Comparison test of the two AUC areas revealed significant difference (P = 0.0474). The presence of calcification and higher cortex involvement ratio were the only findings suggestive of oligodendrogliomas than astrocytic tumors with exclusion of GBMs (P = 0.014 and <0.001, respectively).

Conclusion

Cortex involvement ratio and the presence of calcification with V _e values were diagnostically accurate in identifying oligodendrogliomas. The V _e value calculated from dynamic contrast-enhanced MR imaging could be a supportive tool for differentiating between oligodendrogliomas and astrocytic tumors including GBMs.

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Why fetal neurosurgery?

Abstract

Introduction to the Special Focus Session on Fetal Neurosurgery

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Fetoscopic patch coverage of experimental myelomenigocele using a two-port access in fetal sheep

Abstract

Purpose

This study aims to assess the feasibility and the effectiveness of a fetoscopic myelomeningocele (MMC) coverage using a sealed inert patch through a two-port access, in the sheep model.

Methods

Forty-four fetuses underwent surgical creation of a MMC defect at day 75 and were divided into four groups according to the MMC repair technique, performed at day 90. Group 1 remained untreated. Group 2 had an open surgery using suture of the defect. Groups 3 and 4 underwent defect coverage using a Gore®-polytetrafluoroethylene patch secured with surgical adhesive (Bioglue®), with an open approach (group 3) and a fetoscopic one (group 4). Lambs were killed at term, and histological examinations were performed.

Results

Fetoscopic patch coverage was achieved in all the lambs of group 4. All the fetuses of group 2 had a complete closure of the defect whereas only 38% in group 3 and 14% in group 4. Fetal loss rate seems to be lower in group 4 than in groups 2 and 3.

Conclusion

Fetoscopic coverage of MMC defect can be performed using a sealed patch through a two-port access, but the patch and glue correction may not be the ideal technique to repair fetal MMC.

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Allergic contact dermatitis in preservatives: current standing and future options.

Purpose of review: Preservatives are well known skin sensitizers and represent one of the main causes of contact allergy. The purpose of this article is to review the current state of contact sensitization induced by preservatives and point future alternatives for products' preservation. Recent findings: Isothiazolinones currently are the most common preservatives responsible of contact allergy in Europe and in the United States, and although some regulatory interventions have been taken place, the current contact allergy outbreak is not yet under control. Despite the ban of methyldibromo glutaronitrile from cosmetics in Europe, sensitized patients are still diagnosed, suggesting other nonregulated sources of exposure. Sensitization rates to formaldehyde and formaldehyde-releasers are lower in Europe in comparison with the United States due to stricter regulations regarding their use. Prevalence of contact allergy to parabens has remained stable over the last decades, whereas iodopropynyl butylcarbamate is an emerging allergen with an increasing prevalence. Future alternatives for products' preservation look for a broad antimicrobial spectrum, but with a better safety profile (in terms of sensitization) than the currently available compounds. Summary: Given the high rates of sensitization reported over the last years, timely regulatory actions are urgently required for some preservatives that currently represent a concern for public health. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Defining the minimal clinically important difference for olfactory outcomes in the surgical treatment of chronic rhinosinusitis

Background

Olfactory dysfunction is a common and defining symptom of chronic rhinosinusitis (CRS). Many measures of olfactory dysfunction in CRS are limited by scoring criteria defined within general populations with interpretations of statistical significance to infer clinically meaningful improvement. In this investigation we define a minimal clinically important difference (MCID) for the Brief Smell Identification Test (BSIT) in CRS patients electing endoscopic sinus surgery (ESS).

Methods

A multicenter cohort of 290 adult patients electing ESS for medically recalcitrant CRS were prospectively enrolled between March 2011 and June 2015 and completed BSIT evaluations before and after ESS. Distribution and anchor-based analytic approaches were utilized to define MCID values of the BSIT across patient cofactors.

Results

A total of 92 (∽32%) patients were found to have preoperative olfactory dysfunction (BSIT <9), significantly associated with nasal polyposis (χ² = 35.0; p < 0.001). The effect-size distribution-based approach identified 1.0 as a MCID criterion value between “small” and “medium” effect (range, 0.61-1.52) overall. Significant mean postoperative change (ΔM) was reported for patients with olfactory dysfunction (ΔM = 2.28; p < 0.001), both with (n = 54; ΔM = 2.52; p < 0.001) and without (n = 38; ΔM = 1.95; p < 0.001) nasal polyposis, significantly exceeding the MCID criterion. Anchor-based approaches with regression modeling confirmed associations between MCID values and postoperative changes to olfactory-specific survey responses (p < 0.001).

Conclusion

Clinically meaningful change in BSIT scores may be defined as an absolute value difference of at least 1.0 unit for heterogeneous patients electing ESS for CRS. Significantly exceeding this criterion may be restricted to CRS patients with baseline olfactory dysfunction, regardless of nasal polyposis.

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Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulatio...

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Hot, sleepless nights will get more common with climate change

People in the US stand to lose sleep as the climate warms – and those in hotter countries will be harder hit

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Highly Oriented Atomically Thin Ambipolar MoSe2 Grown by Molecular Beam Epitaxy

ACS Nano

DOI: 10.1021/acsnano.7b02726

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Hot, sleepless nights will get more common with climate change

People in the US stand to lose sleep as the climate warms – and those in hotter countries will be harder hit

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Treatment of Dyslipidemia Using CRISPR/Cas9 Genome Editing

Abstract

Purpose of Review

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) has recently emerged as a top genome editing technology and has afforded investigators the ability to more easily study a number of diseases. This review discusses CRISPR/Cas9’s advantages and limitations and highlights a few recent reports on genome editing applications for alleviating dyslipidemia through disruption of proprotein convertase subtilisin/kexin type 9 (PCSK9).

Recent Findings

Targeting of mouse Pcsk9 using CRISPR/Cas9 technology has yielded promising results for lowering total cholesterol levels, and several recent findings are highlighted in this review. Reported on-target mutagenesis efficiency is as high as 90% with a subsequent 40% reduction of blood cholesterol levels in mice, highlighting the potential for use as a therapeutic in human patients.

Summary

The ability to characterize and treat diseases is becoming easier with the recent advances in genome editing technologies. In this review, we discuss how genome editing strategies can be of use for potential therapeutic applications.

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Treatment of Juvenile Dermatomyositis: An Update

Abstract

The idiopathic inflammatory myopathies of childhood consist of a heterogeneous group of autoimmune diseases characterised by proximal muscle weakness and pathognomonic skin rashes. The overall prognosis of juvenile myositis has improved significantly over recent years, but the long-term outcome differs substantially from patient to patient, suggestive of distinct clinical phenotypes with variable responses to treatment. High doses of corticosteroids remain the cornerstone of therapy along with other immunosuppressant therapies depending on disease severity and response. The advent of biological drugs has revolutionised the management of various paediatric rheumatologic diseases, including inflammatory myopathies. There are few data from randomised controlled trials to guide management decisions; thus, several algorithms for the treatment of juvenile myositis have been developed using international expert opinion. The general treatment goals now include elimination of active disease and normalisation of physical function, so as to preserve normal growth and development, and to prevent long-term damage and deformities. This review summarises the newer and possible future therapies of juvenile inflammatory myopathies, including evidence supporting their efficacy and safety.

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Prediction of Response to Sorafenib in Hepatocellular Carcinoma: A Marker Panel by Multiple Reaction Monitoring-Mass Spectrometry [Research]

Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafenib by MRM-MS, comprising CD5 antigen-like (CD5L), immunoglobulin J (IGJ), and galectin-3-binding protein (LGALS3BP), in HCC patients. This panel was a significant predictor (AUROC > 0.950) of the response to sorafenib treatment, having the best cut-off value (0.4) by multivariate analysis. In the training set, patients who exceeded this cut-off value had significantly better overall survival (median, 21.4 months) than those with lower values (median, 8.6 months; P = 0.001). Further, a value that was lower than this cutoff was an independent predictor of poor overall survival [hazard ratio (HR), 2.728; 95% confidence interval (CI), 1.312-5.672; P = 0.007] and remained an independent predictive factor of rapid progression (HR, 2.631; 95% CI, 1.448-4.780; P = 0.002). When applied to the independent validation set, levels of the cut-off value for triple-marker panel maintained their prognostic value for poor clinical outcomes. On the contrast, the triple-marker panel was not a prognostic factor for patients who were treated with transarterial chemoembolization (TACE). The discriminatory signature of a triple-marker panel provides new insights into targeted proteomic biomarkers for individualized sorafenib therapy.

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Lysine Acetylome Analysis Reveals Photosystem II Manganese-stabilizing Protein Acetylation is Involved in Negative Regulation of Oxygen Evolution in Model Cyanobacterium Synechococcus sp. PCC 7002 [Research]

N-Acetylation of lysine residues represents a frequently occurring post-translational modification widespread in bacteria that plays vital roles in regulating bacterial physiology and metabolism. However, the role of lysine acetylation in cyanobacteria remains unclear, presenting a hurdle to in-depth functional study of this post-translational modification. Here, we report the lysine acetylome of Synechococcus sp. PCC 7002 (hereafter Synechococcus) using peptide prefractionation, immunoaffinity enrichment, and coupling with high-precision liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis of Synechococcus identified 1653 acetylation sites on 802 acetylproteins involved in a broad range of biological processes. Interestingly, the lysine acetylated proteins were enriched for proteins involved in photosynthesis, for example. Functional studies of the photosystem II manganese-stabilizing protein were performed by site-directed mutagenesis and mutants mimicking either constitutively acetylated (K99Q, K190Q, and K219Q) or nonacetylated states (K99R, K190R, and K219R) were constructed. Mutation of the K190 acetylation site resulted in a distinguishable phenotype. Compared to the K190R mutant, the K190Q mutant exhibited a decreased oxygen evolution rate and an enhanced cyclic electron transport rate in vivo. Our findings provide new insight into the molecular mechanisms of lysine acetylation that involved in the negative regulation of oxygen evolution in Synechococcus and creates opportunities for in-depth elucidation of the physiological role of protein acetylation in photosynthesis in cyanobacteria.

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WITHDRAWN: Heralds of parallel MS: Data-independent acquisition surpassing sequential identification of data dependent acquisition in proteomics [Research]

This article has been withdrawn by the authors. This article did not comply with the editorial guidelines of MCP. Specifically, single peptide based protein identifications of 9-19% were included in the analysis and discussed in the results and conclusions. We wish to withdraw this article and resubmit a clarified, corrected manuscript for review.

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The CLASP2 Protein Interaction Network in Adipocytes Links CLIP2 to AGAP3, CLASP2 to G2L1, MARK2, and SOGA1, and Identifies SOGA1 as a Microtubule-Associated Protein [Research]

CLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane. To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes. Using two different commercially available antibodies for CLASP2 and an antibody for epitope-tagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT). We discovered that CLASP2 co-immunoprecipitates (co-IPs) the novel protein SOGA1, the microtubule-associated protein kinase MARK2, and the microtubule/actin-regulating protein G2L1. The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1, glycogen synthase, and glycogenin. Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein. These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology.

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RT @richbamford81 : Don't forget to complete the elearning pall care module before attending this important and valuable day https://t.co/9S…

RT @richbamford81 : Don't forget to complete the elearning pall care module before attending this important and valuable day https://t.co/9S…

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RT @ESSOnews : Interesting @ecancer free seminar on #prostatecancer live from #ASCO17 for healthcare professionals https://t.co/qnABQSj7lC h…

RT @ESSOnews : Interesting @ecancer free seminar on #prostatecancer live from #ASCO17 for healthcare professionals https://t.co/qnABQSj7lC h…

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Reduced monocyte adhesion to aortae of diabetic plasminogen activator inhibitor-1 knockout mice

Abstract

Objective and design

To determine the requirement of plasminogen activator inhibitor-1-knockout (PAI-1) for monocyte adhesion in animals and cells under diabetic conditions.

Methods and subjects

Monocyte adhesion assay, enzyme-linked immunosorbent assay, and Western blotting were used in analyzing samples from PAI-1-knockout (PAI-1-KO) mice or cultured human umbilical vein endothelial cells (HUVEC).

Treatments

Diabetes in PAI-1-KO and wild-type mice was induced by intraperitoneal injection of streptozotocin (STZ). HUVEC was transfected with short interference RNA (siRNA) against PAI-1, tumor necrosis factor-α (TNFα), or toll-like receptor (TLR4), and then was treated with glycated low-density lipoproteins (glyLDL).

Results

The adhesion of monocytes to aortic intima was reduced in PAI-1-KO mice, which was associated with decreased levels of TNFα and monocyte chemotactic protein-1 (MCP-1) in plasma and cardiovascular tissue, and increased abundances of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in cardiovascular tissue compared to wild-type mice. Significant reductions in monocyte adhesion, inflammatory, and fibrinolytic regulators were detected in cardiovascular tissue or plasma in diabetic PAI-1-KO mice compared to wild-type diabetic mice. Transfection of PAI-1, TNFα or TLR4 siRNA to HUVEC inhibited glyLDL-induced monocyte adhesion to EC. PAI-1 siRNA inhibited the abundances of TLR4 and TNFα in EC.

Conclusion

The findings suggest that PAI-1 is required for diabetes-induced monocyte adhesion via interactions with uPA/uPAR, and it also regulates TLR4 and TNFα expression in vascular EC. Inhibition of PAI-1 potentially reduces vascular inflammation under diabetic condition.

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Sectra expands presence in Canada

Swedish PACS vendor Sectra announced it has established a direct sales presence...

Read more on AuntMinnieEurope.com

Related Reading:

Sectra receives Belgian enterprise imaging order

Sectra signs Swedish hospital

Sectra sales, profit increase in Q3

Sectra signs 10-year Dutch deal

Sectra to debut extended image sharing at ECR 2017

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Philanthro-metrics: Mining multi-million-dollar gifts

by Una O. Osili, Jacqueline Ackerman, Chin Hua Kong, Robert P. Light, Katy Börner

The Million Dollar List (MDL, online at http://ift.tt/1pwQApI) is a compilation of publicly announced charitable donations of $1 million or more from across the United States since 2000; as of December 2016, the database contains close to 80,000 gifts made by U.S. individuals, corporations, foundations, and other grant-making nonprofit organizations. This paper discusses the unique value of the Million Dollar List and provides unique insights to key questions such as: How does distance affect giving? How do networks impact million-dollar-plus gifts? Understanding the geospatial and temporal dimensions of philanthropy can assist researchers and policymakers to better understand the role of private funding in innovation and discovery. Moreover, the results from the paper emphasize the importance of philanthropy for fueling research and development in science, the arts, environment, and health. The paper also includes the limitations of the presented analyses and promising future work.

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Correction: Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

by The PLOS Computational Biology Staff

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The new issue is now available.Educational Information Research

Vol.15 No.4

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The new issue is now available.Educational Information Research

Vol.16 No.1

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The new issue is now available.Rinsho Shinkeigaku

Vol.57 No.5

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The new issue is now available.Educational Information Research

Vol.16 No.2

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The new issue is now available.Educational Information Research

Vol.16 No.4

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The new issue is now available.Educational Information Research

Vol.16 No.3

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The new issue is now available.Farumashia

Vol.47 No.8

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The new issue is now available.Educational Information Research

Vol.15 No.3

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The new issue is now available.Educational Information Research

Vol.15 No.2

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The new issue is now available.Educational Information Research

Vol.15 No.1

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The new issue is now available.Journal of Environmental Conservation Engineering

Vol.46 No.4

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The new issue is now available.Journal of Japan Society of Nursing Research

Vol.40 No.1

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The new issue is now available.JAPANESE JOURNAL OF ECOLOGY

Vol.55 No.3

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The new issue is now available.JAPANESE JOURNAL OF ECOLOGY

Vol.55 No.1

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The new issue is now available.JAPANESE JOURNAL OF ECOLOGY

Vol.55 No.2

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The new issue is now available.Educational Information Research

Vol.14 No.4

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