Recovering Wood and McCarthy’s ERP-prototypes by means of ERP-specific procrustes-rotation

Publication date: 1 February 2018
Source:Journal of Neuroscience Methods, Volume 295
Author(s): André Beauducel
BackgroundThe misallocation of treatment-variance on the wrong component has been discussed in the context of temporal principal component analysis of event-related potentials. There is, until now, no rotation-method that can perfectly recover Wood and McCarthy's prototypes without making use of additional information on treatment-effects.New methodIn order to close this gap, two new methods: for component rotation were proposed. After Varimax-prerotation, the first method identifies very small slopes of successive loadings. The corresponding loadings are set to zero in a target-matrix for event-related orthogonal partial Procrustes- (EPP-) rotation. The second method generates Gaussian normal distributions around the peaks of the Varimax-loadings and performs orthogonal Procrustes-rotation towards these Gaussian distributions. Oblique versions of this Gaussian event-related Procrustes- (GEP) rotation and of EPP-rotation are based on Promax-rotation.ResultsA simulation study revealed that the new orthogonal rotations recover Wood and McCarthy's prototypes and eliminate misallocation of treatment-variance. In an additional simulation study with a more pronounced overlap of the prototypes GEP Promax-rotation reduced the variance misallocation slightly more than EPP Promax-rotation.Comparison with Existing Method(s): Varimax- and conventional Promax-rotations resulted in substantial misallocations of variance in simulation studies when components had temporal overlap. A substantially reduced misallocation of variance occurred with the EPP-, EPP Promax-, GEP-, and GEP Promax-rotations.ConclusionsMisallocation of variance can be minimized by means of the new rotation methods: Making use of information on the temporal order of the loadings may allow for improvements of the rotation of temporal PCA components.



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The effect of monitor raster latency on VEPs, ERPs and Brain–Computer Interface performance

Publication date: 1 February 2018
Source:Journal of Neuroscience Methods, Volume 295
Author(s): Sebastian Nagel, Werner Dreher, Wolfgang Rosenstiel, Martin Spüler
BackgroundVisual neuroscience experiments and Brain–Computer Interface (BCI) control often require strict timings in a millisecond scale. As most experiments are performed using a personal computer (PC), the latencies that are introduced by the setup should be taken into account and be corrected. As a standard computer monitor uses a rastering to update each line of the image sequentially, this causes a monitor raster latency which depends on the position, on the monitor and the refresh rate.New methodWe technically measured the raster latencies of different monitors and present the effects on visual evoked potentials (VEPs) and error-related potentials (ERPs). Additionally we present a method for correcting the monitor raster latency and analyzed the performance difference of a code-modulated VEP BCI speller by correcting the latency.Comparison with existing methodsThere are currently no other methods validating the effects of monitor raster latency on VEPs and ERPs.ResultsThe timings of VEPs and ERPs are directly affected by the raster latency. Furthermore, correcting the raster latency resulted in a significant reduction of the target prediction error from 7.98% to 4.61% and also in a more reliable classification of targets by significantly increasing the distance between the most probable and the second most probable target by 18.23%.ConclusionsThe monitor raster latency affects the timings of VEPs and ERPs, and correcting resulted in a significant error reduction of 42.23%. It is recommend to correct the raster latency for an increased BCI performance and methodical correctness.



http://ift.tt/2AP60GI

EJC's biennial report on metastatic soft tissue sarcoma: State of the art and future perspectives

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Melissa Vos, Stefan Sleijfer
In the last decade the limited treatment options for patients with metastatic soft tissue sarcoma have expanded considerably. With the addition of olaratumab to first-line treatment with doxorubicin, the introduction of several new agents in second-line treatment and beyond and other promising agents in the pipeline, perspectives of patients with metastatic soft tissue sarcoma are improving. Due to increasing insight into the biology of the different soft tissue sarcoma subtypes, choice of treatment has become much more histology-driven, although more prognostic and predictive factors are needed to further personalise therapy. This report summarises the current state of the art and discusses the promising developments in the treatment of patients with metastatic soft tissue sarcoma.



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The association between irisin and muscle metabolism in different thyroid disorders

Summary

Background

Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies.

Methods

The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid-related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analyzed in tissue samples from 80 patients with non-toxic multinodular goiter, toxic goiter, Graves' disease and papillary thyroid cancer.

Results

Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency toward lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goiter as compared to Graves' disease, papillary thyroid cancer and controls.

Conclusions

The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.

This article is protected by copyright. All rights reserved.

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Characteristics of polycyclic aromatic hydrocarbons in PM 2.5 emitted from different cooking activities in China

Abstract

Nineteen polycyclic aromatic hydrocarbons (PAHs) in PM_2.5 emitted from five different cooking activities were characterized, and their influencing factors were determined. The total quantified particle-bounded PAH concentrations (ΣPAHs) in the airs from the cooking activities were 4.2–36.5-fold higher than those in corresponding backgrounds. The highest ΣPAHs were seen in cafeteria frying (783 ± 499 ng/m³), followed by meat roasting (420 ± 191 ng/m³), fish roasting (210 ± 105 ng/m³), snack-street boiling (202 ± 230 ng/m³), and cafeteria boiling (150 ± 65 ng/m³). The main influencing factors on the PAH emissions were cooking methods, fat contents in raw materials, and oil consumptions. Four- to six-ringed PAHs had the highest contributions to the ΣPAHs (avg. 87.5%). Diagnostic ratios of individual PAH were similar between the two charbroiling and other three conventional Chinese cooking methods, respectively, demonstrating the dominance of cooking methods in the PAH emissions. Remarkably high benzo(b)fluoranthene/benzo(k)fluoranthene (BbF/BkF) ratio (8.31) was seen in the snack-street boiling, attributed to the coal combustion as cooking fuel. Both fluoranthene/(fluoranthene + pyrene) [FLT/(FLT + PYR)] and benzo(a)anthracene/(benzo(a)anthracene + chrysene) [BaA/(BaA + CHR)] ratios were higher for the oil-based cooking than those from the water-based ones. In addition, two ratios of indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene + benzo(g,h,i)perylene) [IPY/(IPY + BPE)] and benzo(a)pyrene/(benzo(a)pyrene + benzo(g,h,i)perylene) [BaP/(BaP + BPE)] were higher for two charbroiling than the three conventional Chinese cooking methods. The characterization work in this study is particularly important since cooking is a potential contributor of atmospheric PAHs in urban China. Carcinogenic potencies of PAHs were assessed by comparison with the air quality guideline and health risk estimation. The BaP and BaP equivalent were higher for the oil-based than the water-based cooking activities.

http://ift.tt/2AAGTa6

Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats’ associated simultaneous immunohistochemical expression of TGF-β1+, α-ER+, and BMPR1B-

Abstract

Objectives

TGF-β1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-β1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-β1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens.

Materials and methods

A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-β1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen.

Results

All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-β1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-β1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased.

Conclusion

The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-β1+/α-ER+ inducing the presence of α-SMA⁺, whereas BMPR1B and Runx-2 were suppressed.

Clinical relevance

The prolonged administration of alendronate alters osteoneogenesis and induces an unusual microenvironment in the bone that seems to imitate the physiological tissue damage that culminates in the loss of the functional layer of endometrium.

http://ift.tt/2j9kMhf

The influence of early life stress on the integration of emotion and working memory

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Sophie Metz, Sabine Aust, Yan Fan, Luisa Bönke, Zjala Harki, Matti Gärtner, Malek Bajbouj, Simone Grimm
IntroductionEarly life stress (ELS) impacts emotional and cognitive competences. We aimed to investigate whether the effects of ELS on working memory (WM) performance depend on the valence of the stimuli.MethodsBetween January and October 2015, we recruited (N=31) healthy subjects with (N=15) and without (N=16) ELS experiences. Participants performed a WM-task with emotional stimuli.ResultsResults show a trend towards decreased WM accuracy in subjects with ELS experiences (p=.06) with increased WM accuracy (p=.08) and an altered pattern of BOLD responses in the left posterior cingulate cortex (PCC)/precuneus (p<.001) and the rostral anterior cingulate cortex (rACC) (p<.01) in response to negative stimuli.LimitationsThe small sample size and potential confounding factors should be considered when interpreting the results.ConclusionOur data suggests that negative valence influences cognitive performance and brain activity in subjects with ELS experiences.



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Cognitive, neurohistological and mortality outcomes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: The impact of diabetes and aging

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Amanda Nunes Santiago, Emilene Dias Fiuza Ferreira, Rúbia Maris Weffort de Oliveira, Humberto Milani
Chronic cerebral hypoperfusion (CCH) may be involved in the etiology of aging-related dementias, and several risk factors contribute to their development and/or aggravation. We previously reported on the development of the 4-VO/ICA model of CCH, and the impact of hypertension on the cognitive and histological outcomes of CCH. Here, we advanced those studies by investigating how 4-VO/ICA alone or in combination with diabetes affects survival, body weight and cognitive performance in both young and middle-aged rats. Subsequently, middle-aged rats were examined for the impact of diabetes on CCH-induced neurodegeneration, white matter damage, and glial cells response. Diabetes alone reduced body weight and increased mortality rate slightly in young rats; these effects were striking, however, in the older animals. After CCH alone, neither body weight nor mortality rate changed significantly in both age groups. However, when CCH was combined with diabetes, mortality rate increased significantly in both aged groups. Young rats were cognitively asymptomatic to CCH, but they became 'mildly' impaired after CCH combined with diabetes. In middle-aged rats, CCH severely impaired memory, which was significantly worsened by diabetes. Moreover, diabetes aggravated neurodegeneration in the hippocampus and white matter injury in the corpus callosum and it promoted glial activation in the hippocampus and white matter of CCH middle-aged rats. These data suggest that diabetes interacts synergistically with age and reduces the capacity of the brain to adequately respond to CCH and highlight the importance of associating risk factors in the preclinical investigation of age-related cerebrovascular diseases physiopathology and potential therapies.

Graphical abstract

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Factors Correlating With Microsurgical Performance: A Clinical and Experimental Study

Publication date: Available online 1 December 2017
Source:Journal of Surgical Education
Author(s): Mark V. Schaverien, Jun Liu, Charles E. Butler, Jesse C. Selber
BackgroundMicrosurgery is one the most complex surgical skills to master. The factors correlating with microsurgical performance, however, are poorly understood. Understanding these factors will aid in the training and assessment of microsurgeons.MethodsA total of 29 microsurgery fellows enrolled in a dedicated 1-year microsurgery fellowship were included in the study. For the clinical evaluations, microsurgical anastomosis performance was evaluated during multiple procedures in the operating room at the start, midpoint, and end of the fellowship by all departmental faculty using a validated microsurgical assessment tool. For the laboratory evaluations, blinded video recordings of each fellow performing an arterial femoral anastomosis in a live rat model at the start and end of the fellowship were evaluated using 3 validated microsurgical global ratings scale tools. Correlations between performance and the factors assessed by the tools were evaluated.ResultsIn the clinical study there were a total of 474 anastomosis evaluations; clinical performance correlated best with speed, instrument handling, and motion. In the laboratory study 58 evaluations were conducted, and performance tracked most closely with instrument handling, flow of operation, and operative steps, as well as correlating significantly inversely with time taken. The most common errors committed were unequal stitch bites, wrong grasp/damage tissue, and loose knot.ConclusionsSpeed, both subjective and objective, instrument handling, operative flow, and motion, were relevant to performance of a microsurgical anastomosis. A prospective trial is now necessary to determine whether these factors should be considered in definitions of competency in microsurgery training pathways.



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Radiation therapy improves disease-specific survival in women with Stage II endometrioid endometrial cancer—Brachytherapy may be sufficient

Publication date: Available online 2 December 2017
Source:Brachytherapy
Author(s): Chika R. Nwachukwu, Rie Von-Eyben, Elizabeth A. Kidd
PurposeTo evaluate disease-specific survival (DSS) outcomes in Stage II endometrioid endometrial cancer (EC) patients based on pathology and treatment information including adjuvant radiotherapy and lymph node assessment.Methods and MaterialsUsing the Surveillance, Epidemiology, and End Results database, 2877 patients with Stage II EC diagnosed between 2004 and 2012 treated with radiation were identified. DSS was determined for different modalities of radiation. Kaplan–Meier estimates of survival and Cox regression modeling were used to explore the risk associated with various factors on DSS.ResultsThe 4-year DSS for the study population was 90%. Radiation was associated with improved 4-year DSS when compared to no radiotherapy (p = 0.03). Patients with Grade 2 and 3 tumors had improved 4-year DSS with radiation (94% vs. 90%, p = 0.02 and 81% vs. 73%, p = 0.15), respectively, but no differences in DSS when vaginal brachytherapy alone was compared with external beam alone or both. Patients with Grade 2 (p = 0.002) and Grade 3 (p < 0.001) tumors without a lymph node dissection (LND) had worse DSS compared to patients with any LND. Patients with Grade 3 tumors without an LND who received radiation showed improved DSS (p = 0.008). Multivariable analysis revealed that age >60 years (p < 0.001), Grade 3 (p < 0.001), no radiotherapy (p = 0.05), and no LNDs (p < 0.001) were significant prognostic factors for worse DSS.ConclusionsAdjuvant radiation, whether delivered by brachytherapy or external beam radiation, is associated with improved DSS in Stage II EC patients with high-grade tumors, therefore brachytherapy may be sufficient.



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Initial clinical assessment of “center-specific” automated treatment plans for low-dose-rate prostate brachytherapy

Publication date: Available online 1 December 2017
Source:Brachytherapy
Author(s): Mustafa Ege Babadagli, John Doucette, Nawaid Usmani, John Amanie, Albert Murtha, Don Yee, Mohammad Jamaluddin, Ron S. Sloboda
PurposeTo report results of an initial pilot study assessing iodine-125 prostate implant treatment plans created automatically by a new seed-placement method.Methods and MaterialsA novel mixed-integer linear programming method incorporating spatial constraints on seed locations in addition to standard dose–volume constraints was used to place seeds. The approach, described in detail elsewhere, was used to create treatment plans fully automatically on a retrospective basis for 20 patients having a wide range of prostate sizes and shapes. Corresponding manual plans used for patient treatment at a single institution were combined with the automated plans, and all 40 plans were anonymized, randomized, and independently evaluated by five clinicians using a common scoring tool. Numerical and clinical features of the plans were extracted for comparison purposes.ResultsA full 51% of the automated plans were deemed clinically acceptable without any modification by the five practitioners collectively versus 90% of the manual plans. Automated plan seed distributions were for the most part not substantially different from those for the manual plans. Two observed shortcomings of the automated plans were seed strands not intersecting the prostate and strands extending into the bladder. Both are amenable to remediation by adjusting existing spatial constraints.ConclusionsAfter spatial and dose–volume constraints are set, the mixed-integer linear programming method is capable of creating prostate implant treatment plans fully automatically, with clinical acceptability sufficient to warrant further investigation. These plans, intended to be reviewed and refined as necessary by an expert planner, have the potential to both save planner time and enhance treatment plan consistency.



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Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy

Publication date: Available online 2 December 2017
Source:Brachytherapy
Author(s): Susan Y. Wu, Lauren Boreta, Ashley Wu, Joey P. Cheung, J. Adam M. Cunha, Katsuto Shinohara, Albert J. Chang
PurposeHydrogel spacers have been suggested to limit rectal radiation dose with improvements in clinical outcomes in patients undergoing external beam radiation treatment for prostate cancer. No studies to date have assessed the utility and dosimetric effect of SpaceOAR (Augmenix, Inc, Waltham, MA), the only Food and Drug Administration–approved hydrogel rectal spacer, for high-dose-rate (HDR) brachytherapy.MethodsEighteen consecutive patients scheduled for HDR brachytherapy in the treatment of prostate cancer underwent transperineal ultrasound-guided placement of 10 cc of SpaceOAR hydrogel following catheter implantation. Treatment plans were generated using an inverse planning simulated annealing algorithm. Rectal dosimetry for these 18 patients was compared with the 36 preceding patients treated with HDR brachytherapy without SpaceOAR.ResultsFifty-four plans were analyzed. There was no difference in age, pretreatment prostate-specific antigen, Gleason score, clinical stage, prostate volume, or contoured rectal volume between those who received SpaceOAR and those who did not. Patients who received SpaceOAR hydrogel had significantly lower dose to the rectum as measured by percent of contoured organ at risk (median, V80 < 0.005% vs. 0.010%, p = 0.003; V75 < 0.005% vs. 0.14%, p < 0.0005; V70 0.09% vs. 0.88%, p < 0.0005; V60 = 1.16% vs. 3.08%, p < 0.0005); similar results were seen for rectal volume in cubic centimeters. One patient who received SpaceOAR developed a perineal abscess 1 month after treatment.ConclusionsTransperineal insertion of SpaceOAR hydrogel at the time of HDR brachytherapy is feasible and decreases rectal radiation dose. Further investigation is needed to assess the clinical impact of this dosimetric improvement and potential toxicity reduction.



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Pulmonary papillary adenocarcinoma with Aspergillus versicolor infection in a dog

Publication date: March 2018
Source:Medical Mycology Case Reports, Volume 19
Author(s): Rathiymaler Maniam, Gayathri Thevi Selvarajah, Mazlina Mazlan, Leslie Thian Lung Than
Papillary adenocarcinoma of the lungs is the most common primary lung adenocarcinoma, with the feature of papillary-like structure formation by cells. A dog was presented with the primary complaint of vomiting, hyporexia and increased respiratory effort. Thoracic radiography revealed increased soft tissue radiopacity of the right cranial lung lobe suggestive of possible consolidation or collapsed lung lobe, with generalised miliary nodular pattern throughout the other lung fields. The dog was euthanized humanely and necropsy was performed. Histopathology confirmed the diagnosis of primary pulmonary lung neoplasm (papillary adenocarcinoma) with Aspergillus versicolor infection identified through fungal culture and PCR. There have been several reports on humans and dogs with fungal infections that often mimic or coexist with pulmonary neoplasm. This is the first documented report of A. versicolor isolated from a lung neoplasm in a dog in Malaysia.



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Hypercoagulability and Vascular Disease

Publication date: Available online 1 December 2017
Source:Hematology/Oncology Clinics of North America
Author(s): Ali T. Taher, Maria Domenica Cappellini, Rayan Bou-Fakhredin, Daniel Coriu, Khaled M. Musallam

Teaser

The presence of a high incidence of thrombotic events, mainly in nontransfusion-dependent β-thalassemia syndromes, has led to the identification of a hypercoagulable state in thalassemia patients. This article highlights the mechanisms leading to hypercoagulability in thalassemia. It also discusses the clinical experience and available evidence on prevention and management approaches.


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Accreditation of service hospitals: Time to move towards state of readiness

Publication date: Available online 2 December 2017
Source:Medical Journal Armed Forces India
Author(s): K.M. Adhikari, Deepak Joshi, Rakesh Gupta




http://ift.tt/2iECIDb

Sclerosing stromal cell tumor of ovary

Publication date: Available online 2 December 2017
Source:Medical Journal Armed Forces India
Author(s): Shazia Khan, Virendra Singh, I.D. Khan, Sujatha Panda




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Th1 epitope peptides induce protective immunity against Rickettsia rickettsii infection in C3H/HeN mice

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Pengcheng Wang, Xiaolu Xiong, Jun Jiao, Xiaomei Yang, Yongqiang Jiang, Bohai Wen, Wenping Gong
Rickettsia rickettsii is the causative pathogen of Rocky Mountain spotted fever (RMSF). Adr2, YbgF and OmpB are protective antigens of R. rickettsii. In this study, 90 candidate peptides were selected from these antigens based on their high-affinity binding capacity for the MHC class II molecule H2 I-A or H2 I-E using bioinformatic methods. Six peptides were determined using ELISPOT assay to be immunodominant based on the IFN-γ recall responses of CD4⁺ T cells from mice immunized with R. rickettsii. Six nucleotide sequences encoding the immunodominant peptides were linked in series and inserted into a plasmid for expression in Escherichia coli cells, resulting in a new, recombinant polypeptide termed GWP. After immunization and challenge, the rickettsial load or histopathological lesions in the organs of mice immunized with GWP or pooled peptides was significantly lower than that in organs of mice immunized with PBS or the individual peptide OmpB399. An in vitro neutralization test revealed that sera from mice immunized with GWP, OmpB399, or pooled peptides reduced R. rickettsii adherence to, and invasion of, vascular endothelial cells. Furthermore, significantly higher levels of IgG, IgG1, or IgG2a were detected in sera from mice immunized with GWP or pooled peptides, and significantly higher levels of IFN-γ or TNF-α secreted by CD4⁺ T cells from R. rickettsii-infected mice were detected after immunization with GWP. Altogether, our results indicated that polypeptides, especially GWP, could induce a Th1-type immune response against R. rickettsii infection, which might contribute to the rational design of peptide-based vaccines for RMSF.



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An in vitro cell-based potency assay for pharmaceutical type A botulinum antitoxins

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Amram Torgeman, Eran Diamant, Lilach Levin, Alon Ben David, Eyal Epstein, Meni Girshengorn, Ohad Mazor, Ronit Rosenfeld, Ran Zichel
Botulism therapy relies on passive immunization with antitoxin. The mouse neutralization test is the only pharmacopeia assay to measure the potency of antitoxin preparations. Herein, we present an in vitro cell-based assay for the measurement of pharmaceutical type A antitoxin potency. Accuracy, reproducibility and compatibility with the mouse bioassay were demonstrated using different batches of standard antitoxin and toxin preparations. The established assay may substantially reduce the use of laboratory animals in the process of pharmaceutical antitoxin production.



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Selection of vaccine strains for serotype O foot-and-mouth disease viruses (2007–2012) circulating in Southeast Asia, East Asia and Far East

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Mana Mahapatra, Sasmita Upadhyaya, Sharie Aviso, Aravindh Babu, Geoff Hutchings, Satya Parida
Foot-and-mouth disease (FMD) is endemic in Southeast Asia (SEA) and East Asia with circulation of multiple serotypes and multiple genotypes within each serotype of the virus. Although countries like Japan and South Korea in the Far East were free of FMD, in 2010 FMD serotype O (O/Mya-98) outbreaks were recorded and since then South Korea has experienced several FMD outbreaks despite regular vaccination. In this study a total of 85 serotype O FMD viruses (FMDV) isolated from 2007 to 2012 from SEA, East Asia and Far East were characterized by virus neutralisation tests using antisera to four existing (O/HKN/6/83, O/IND/R2/75, O/SKR/2010 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains, and by full capsid sequencing. Serological studies revealed broad cross-reactivity with the vaccine strains; O/PanAsia-2 exhibited a good match with 95.3%, O/HKN/6/83 with 91.8%, O/IND/R2/75 with 80%, and the putative strain O/MYA/2009 with 89.4% isolates employed in this study. Similarly O/PanAsia-2 and O/IND/R2/75 vaccines showed a good match with all eight viruses belonging to O-Ind-2001d sublineage whereas the vaccines of O/Mya-98 lineage, O/MYA/2009 and O/SKR/2010 exhibited the lowest match indicating their unsuitability to protect infections from O-Ind-2001d viruses. A Bayesian analysis of the capsid sequence data indicated these circulating viruses (n = 85) to be of either SEA or Middle East-South Asian (ME-SA) topotype. The ME-SA topotype viruses were mainly detected in Lao PDR, Vietnam, Myanmar and Thailand reflecting the trade links with the Indian subcontinent, and also within the SEA countries. Implications of these results in the context of FMD control in SEA and East Asian countries are discussed.



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Differences between vaccinated and unvaccinated women explain increase in non-vaccine-type human papillomavirus in unvaccinated women after vaccine introduction

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Lili Ding, Lea E. Widdice, Jessica A. Kahn
The aim of this study was to determine whether an observed increase in non-vaccine-type human papillomavirus (HPV) in unvaccinated women during the first eight years after vaccine introduction may be explained by differences in demographics or sexual behaviors, instead of type replacement. We analyzed data from three cross-sectional surveillance studies of 13–26 year-old women (total N = 1180). For women recruited from a health department clinic, older age (OR = 1.4, 95% CI: 1.2–1.6) and consistent condom use with main partner in the past 3 months (OR = 11.6, 95% CI: 3.4–40) were associated with being unvaccinated. For women recruited from a teen health center African American race (OR = 0.2, 95% CI: 0.07–0.7) and having Medicaid health insurance (OR = 0.3, 95% CI: 0.1–0.7) were inversely associated with being unvaccinated. The observed increase in non-vaccine-type HPV prevalence in unvaccinated women may be explained by differences between unvaccinated and vaccinated women.



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Conflicting results in article describing “HPV-vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis”

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): L. Andersson




http://ift.tt/2AODvsJ

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): English D. Willis, Meredith Woodward, Elizabeth Brown, Zoran Popmihajlov, Patricia Saddier, Paula W. Annunziato, Neal A. Halsey, Anne A. Gershon
BackgroundZoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed.MethodsAll post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed.ResultsA total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination.ConclusionsThe safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.



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In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Natiely S. Sales, Jamile R. Silva, Luana R.M.M. Aps, Mariângela O. Silva, Bruna F.M.M. Porchia, Luís Carlos S. Ferreira, Mariana O. Diniz
In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8⁺ T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8⁺ T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines.



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Editorial Board/Aims and Scope

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52





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Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Patricia González Cano, Lakshman N.A. Gamage, Kristen Marciniuk, Connie Hayes, Scott Napper, Sidney Hayes, Philip J. Griebel
Bacteriophage are structurally stable in the gastro-intestinal tract and have favorable traits of safety, stability, ease of production, and immunogenicity. These attributes make them potential candidates as oral vaccine delivery vehicles but little is known about their capacity to induce mucosal immune responses in the small intestine. Whole body imaging of mice confirmed lambda bacteriophage (LP) were distributed throughout the gastro-intestinal tract 24 h after oral delivery. In newborn calves, targeted delivery of LP within the small intestine confirmed LP were immunogenic in a dose-dependent manner and were taken up by Peyer's patches. LP-specific IgA responses were induced within both Peyer's patches and draining mesenteric lymph nodes. A lambda display phage (LDP) was constructed to present three immunogenic disease specific epitopes (DSE) from cervid prion protein (amino acids 130–140 [YML]; 163–170 [YRR]; and 171–178[YRR]) fused to phage capsid head protein D (LDP-DSE). Targeted delivery of purified LDP-DSE to intestinal segments induced IgA responses to all three peptide epitopes. Further, delivery of bacteria expressing soluble D-DSE also induced epitope-specific IgA responses in the targeted Peyer's patches. These are the first studies to report use of LDP to induce epitope-specific IgA responses in the small intestine andconfirm Peyer's patchesfunction as a site for LP uptake. Furthermore, IgA responses to peptide epitopes on LDP were observed in the absence of a mucosal adjuvant. These observations confirm LDP have the capacity to function as a mucosal delivery vehicle with protein D as an effective carrier for peptide epitopes.



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Francisella noatunensis subspecies noatunensis clpB deletion mutant impairs development of francisellosis in a zebrafish model

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Elisabeth O. Lampe, Carl Zingmark, Julia I. Tandberg, Ida Marie P. Thrane, Espen Brudal, Anders Sjöstedt, Hanne C. Winther-Larsen
BackgroundFrancisella noatunensis ssp. noatunensis (F.n.n.) is the causative agent of francisellosis in Atlantic cod and constitutes one of the main challenges for future aquaculture on this species. A facultative intracellular bacterium like F.n.n. exert an immunologic challenge against which live attenuated vaccines in general are most effective. Thus, we constructed a deletion in the F.n.n. clpB gene as ΔclpB mutants are among the most promising vaccine candidates in human pathogenic Francisella.PurposeCharacterization of F.n.n. ΔclpB using primary Atlantic cod head kidney leukocytes, the zebrafish embryo and adult zebrafish model with focus on potential attenuation, relevant immune responses and immunogenic potential.Main resultsInterleukin 1 beta transcription in Atlantic cod leukocytes was significantly elevated from 24 to 96 h post infection with F.n.n. ΔclpB compared to F.n.n. wild-type (wt). Growth attenuation of the deletion mutant in zebrafish embryos was observed by fluorescence microscopy and confirmed by genome quantification by qPCR. In the immunization experiment, adult zebrafish were immunized with 7 × 10⁶ CFU of F.n.n. ΔclpB before challenge four weeks later with 6 × 10⁸ CFU of F.n.n. wt. One day after challenge, immunized zebrafish responded with significantly lower interleukin 8 levels compared to the non-immunized control. Immunized fish were protected against the acute mortality observed in non-immunized zebrafish after challenge and bacterial genomes quantified by qPCR were reduced to a minimum 28 days post challenge, indicating protective immunity stimulated by F.n.n. ΔclpB.ConclusionDeletion mutation of clpB in F.n.n. causes in vitro and in vivo attenuation and elicits a protective immune response in adult zebrafish against a lethal dose of F.n.n. wt. Taken together, the results presented increases the knowledge on protective immune responses against F.n.n.



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Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Ya Li, Huimin Cao, Yiping Li, Zhixin Li, Xiaomin Wei, Rui Jiao, Peng Cheng, Xiaoran Liu, Yanjie Ma, Yun Xing, Jiali Tang, Min Wang, Taiming Li
Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β cells leads to impaired glucose metabolism and its attendant complications. IA2(5)P2-1, a potent immunogenic carrier which designed by our laboratory, can induce high titer specific antibodies when carry a B cell epitope, such as B cell epitopes of DPP4, xanthine oxidase, and Urate transporter protein. In this report, we describe a novel multi-epitope vaccine composing a peptide of DPP4, an anti-diabetic B epitope of Insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in non-obese diabetic (NOD) mice successfully induced specific anti-DPP4 antibody, inhibited plasma DPP4 activity, and increased serum GLP-1 level. Moreover, this antibody titer was correlated with the dose of immunization (20μg, 100μg). Inoculation of this vaccine in NOD mice significantly control blood glucose level, improved glucose excursion and increased insulin level in vivo. Consistent with a lower diabetic and insulitis incidence, a induced splenic T cells proliferation and tolerance were observed. IFN-γ secretion reduced and IL-10 increased significantly in the D41-IA2(5)-P2-1 treated mice compared to P277 and control group due to the potential immunomodulatory effect of the epitope in the vaccine. Immunohistochemical analysis and cytometry showed a rebalance of Th1/Th2 in NOD mice. Our results demonstrate that this multi-epitope vaccine may serve as a promising therapeutic approach for type 1 diabetes.



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Response to Curran and Mrkvan, Letter to the Editor: Response to publication by Hoshi SL et al.: Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Shu-ling Hoshi, Masahide Kondo, Ichiro Okubo




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No conflicting results in the article “HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway”

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Berit Feiring, Ida Laake, Lill Trogstad




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Immune responses to intradermal and intramuscular inactivated influenza vaccine among older age group

Publication date: 19 December 2017
Source:Vaccine, Volume 35, Issue 52
Author(s): Kobporn Boonnak, Jittima Dhitavat, Narumon Thantamnu, Nathamon Kosoltanapiwat, Montida Auayporn, Li Jiang, Pilaipan Puthavathana, Punnee Pitisuttithum
BackgroudInfluenza viruses cause substantial morbidity, especially in older age groups. Thus, they are amongst high priority groups for routine vaccination. However, vaccine-induced immune responses and effectiveness were reported as relatively low. This study aims to systemically compare the immune responses elicited by intramuscular (IM) and intradermal (ID) injections with inactivated seasonal influenza vaccine among the older age group.MethodsA prospective, open-label, randomized study with a total of 221 adults (>60 years) were enrolled and randomized into 2 groups. Group I (n = 111) received an IM inactivated seasonal influenza vaccine while Group II (n = 110) received the same vaccine ID. Demographics and co-morbidity were collected at baseline. Safety data was collected 3 days post-vaccination using diary card. HAI, NAb and NAI titers were assessed prior to vaccination and at 30, 45, and 60 days post-vaccination. Data was analyzed using SPSS 11.5.ResultsBoth groups had similar BMI and co-morbidity. For ID and IM groups, significant differences were observed for seroconversion rate measured using HAI against H1N1 and H3N2 (58/111 vs 44/110 and 68/111 vs 54/110, respectively) being higher for those aged 60–65 years. However, no differences in HI antibody against B/Phuket were seen. For ID route, history of hyperlipidemia and hypertension were factors associated with high seroconversion rate towards influenza A (p = .001). The seroconversion rate risk ratio were 1.31 and 1.25 (p < .05) against A/California/07/09(H1N1) and A/Songkha/308/13 (H3N2), respectively. Interestingly, the GMT (95% CI) of baseline NAI antibodies among both groups were high (56.57 and 54.01 in the ID and IM groups, respectively). A 4-fold increase measured by NAI against A/California/07/09 (H1N1) were detected in 16.67% and 20% of participants who received ID or IM vaccination, respectively.ConclusionsThe seroconversion rates of HAI, NAb and NAI were modest, especially in those >65 years of age. However, it was higher in the ID group as compared to the IM group.Clinical trial registration: NCT02101749



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Vaccination with a human parainfluenza virus type 3 chimeric FHN glycoprotein formulated with a combination adjuvant induces protective immunity

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): R. Garg, R. Brownlie, L. Latimer, V. Gerdts, A. Potter, S. van Drunen Littel-van den Hurk
Human parainfluenza virus type 3 (PIV3) is a major cause of lower respiratory disease i.e. bronchitis, bronchiolitis or pneumonia, in infants and young children. Presently there is no licensed vaccine against PIV3. To produce an effective subunit vaccine, a chimeric FHN glycoprotein consisting of the N-terminal ectodomain of the fusion (F) protein linked to the haemagglutinin-neuraminidase (HN) protein without transmembrane domain, and secreted forms of the individual F and HN glycoproteins, were expressed in mammalian cells and purified. Mice and cotton rats were immunized intramuscularly (IM) with FHN or both F and HN proteins (F + HN), formulated with poly(I:C) and an innate defense regulator peptide in polyphosphazene (TriAdj). Significantly higher levels of systemic virus-neutralizing antibodies were observed in mice and cotton rats immunized with FHN/TriAdj when compared to animals immunized with the combination of F and HN proteins (F + HN/TriAdj). As PIV3 is a pneumotropic virus, another goal is to produce an effective mucosal subunit vaccine. Intranasal (IN) administration with FHN/TriAdj resulted in mucosal IgA production in the lung and virus neutralizing antibodies in the sera. After PIV3 challenge no virus was detected in cotton rats immunized with FHN/TriAdj regardless of the route of delivery. Protective immunity against PIV3 was also induced by FHN/TriAdj in hamsters. In conclusion, the FHN protein formulated with TriAdj has potential for development of a safe and effective vaccine against PIV3.



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Editorial Board/Aims and Scope

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51





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The frontline of controlled human malaria infections: A report from the controlled human infection models Workshop in Leiden University Medical Centre 5 May 2016

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Meta Roestenberg, Benjamin Mordmüller, Chris Ockenhouse, Annie Mo, Maria Yazdanbakhsh, Peter G. Kremsner
Controlled Human Malaria Infection (CHMI) is the most practiced controlled human infection model nowadays and there is an exponential increase in implementation of the model worldwide. During the Controlled Human Infection Models Workshop in Leiden, one day was dedicated to the discussion of the advances made and gaps in Controlled Human Malaria Infection (CHMI) trials. Factors contributing to this impressive expansion in the number of CHMI trials have been related to the ability to perform CHMI using injectable cryopreserved sporozoites (a product from Sanaria Inc. – PfSPZ Challenge), the development of a transmission blocking CHMI model and the need to test more vaccine candidates particularly in the field of whole-sporozoite vaccine development. However, with an increasing number of CHMI trials being undertaken, in an ever-growing number of trial sites, heterogeneity in trial design may compromise universal interpretation of results and require an ongoing dialogue on the need and feasibility of standardization. At the workshop, CHMI investigators convened to share their experiences in CHMI trials and discuss the possibilities for future trials.



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Controlled human infections

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Meta Roestenberg, Annie Mo, Peter G. Kremsner, Maria Yazdanbakhsh
The principle of deliberately infecting humans with infectious agents in a controlled setting, so-called controlled human infections (CHI), is not novel. Many CHI models have a long history and were established decades ago such as the intentional exposure to yellow fever and dengue performed in the 1900's (Reed, 1902) [2]. In these times bioethics and scientific reasoning were in their infancy. Nowadays, clinical trials are highly regulated and CHI are executed worldwide. Controlled human malaria infections and influenza infections are the two most frequently practiced. Others are experiencing a revival or are being carefully developed. Because CHI models test the efficacy of promising vaccine or drug candidates early in clinical development, they offer the potential to decrease the number of failing phase 2 and 3 trials, reducing risks for patients and saving costs and efforts.In addition, CHI models provide unprecedented opportunities to dissect the physiological, immunological and metabolic changes that occur upon infection. However, it is clear that controlled infections require careful deliberation of safety, ethics, quarantine, scientific output and the production of infectious material.An independent international workshop was hosted by the Leiden University Medical Centre in The Netherlands, bringing together clinical investigators, basic scientists, regulators, funders and policy makers from 22 different countries to discuss the opportunities and challenges in CHI. The aim of the workshop was to discuss CHI as a tool to advance science, drug and vaccine development, share the challenges of establishing a CHI model with specific focus on neglected tropical diseases and the possibilities to transfer models to endemic sites. Noticeably, among the 128 participants were clinical investigators from ten different countries in Sub-Saharan Africa. An important dimension of the meeting was to give the floor to young established clinicians and scientists to voice their perspective on the future of CHI models.



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CAPiTA: The urine antigen detection (SSUAD) was not validated for PCV13 vaccinated patients

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Dirk Marc Van Renterghem




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Potential for a booster dose of rotavirus vaccine to further reduce diarrhea mortality

Publication date: 18 December 2017
Source:Vaccine, Volume 35, Issue 51
Author(s): Eleanor Burnett, Ben A. Lopman, Umesh D. Parashar
Concern has grown that children vaccinated against rotavirus in developing countries may be vulnerable to rotavirus diarrhea in the second year of life due to waning immunity. Adding a booster dose of rotavirus vaccine at 9 or 12 months of age with measles vaccine has been suggested as a strategy to address this. We evaluated the hypothetical potential benefits of a booster dose on reduction of rotavirus mortality. The projected number of deaths averted were calculated using national level full series vaccination coverage, estimated national rotavirus deaths by week of age, and VE at <12 months of age and ≥12 months of age derived from the published literature. We assumed three functional forms of waning based on the VE estimates: stepwise, linear, and logarithmic. We modeled three potential boosting scenarios: (a) reduced VE waning in the second year of life by 50%, (b) reestablished second year of life VE to the levels in the first year of life, and (c) boosted first year VE by 50% of the difference between VE in the first and second years. To express uncertainty resulting from the parameters, each of the nine models were run 1000 times using a random sample of input values. Across all WHO regions, with the stepwise models we estimated a median of 9800 (95%CI: 9400, 10,200), 19,600 (95%CI: 18,800, 20,400), and 29,400 (95%CI: 28,200, 30,700) additional rotavirus deaths averted in the reduced VE waning, reestablished VE, and boosted VE scenarios. These estimates were highly sensitive to the assumed functional form of waning with approximately 65–80% fewer deaths averted if immunity waned in a linear or logarithmic fashion compared to the stepwise model. While these projections will benefit from improved input data points, our resultsinform consideration of booster doses of rotavirus vaccine.



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Maternal early pregnancy vitamin D status in relation to low birth weight and small-for-gestational-age offspring

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Huiping Wang, Yanfeng Xiao, Lan Zhang, Qiong Gao
Maternal vitamin D deficiency is an independent risk factor for fetal growth. We examined the associations between maternal vitamin D status (defined by 25-hydroxyvitamin D [25(OH)D]) at the first prenatal visit and measures of newborn and placental weight, in a large China cohort of singleton, term, live births. From July 2015 to June 2016, women delivering singleton, term, live births with 25(OH)D measured at a first prenatal visit (N=747). Birth weight, placental weight, the placental to fetal weight ratio, and small for gestational age (SGA) were measured. The relationship between levels of 25(OH)D and SGA were evaluated using univariate and multivariate regression analysis. Vitamin D deficiency was defined as 25(OH)D less than 20ng/ml.In those women, 76.9% (95%CI: 74%–78%) were defined as vitamin D deficiency. Incidence of SGA was also high (13.3%; 95%CI: 10.8%–15.7%). We found a nonlinear relation between 25(OH)D and birth weight as well as head circumference (P<0.01). Birth weight and head circumference increased by 69 [95%CI: 38–122] g and 0.31 (0.22–0.40) cm, respectively, per 1ng/ml increase in maternal 25(OH)D up to 20ng/ml and then leveled off thereafter. The SGA distribution across the 25(OH)D quartiles ranged between 3.7% (fourth quartile) to 24.1% (first quartile). For each 1 unit decrease of plasma concentration of 25(OH)D, the unadjusted and adjusted risk of SGA increased by 19% (odds ratio 1.19 [95% CI 1.13–1.25], P<0.001) and 9% (1.08 [1.03–1.16], P=0.009), respectively. In a multivariate model using the vitamin D deficiency vs. other together with the clinical variables, the adjusted risk of SGA increased by 205% (odds ratio 3.05 [95% CI 2.24–4.40], P=0.001). Maternal vitamin D insufficiency is common during pregnancy and is independently associated with low birth weight and high risk of SGA in term infants.



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Vitamin D in Saudi Arabia: Prevalence,distribution and disease associations

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Nasser M. Al-Daghri
More than 33 years have passed since the first paper highlighting vitamin D deficiency as a public health concern in Saudi Arabia was published in 1983. Despite "early" detection,it wasn't until the year 2010 where the interest in vitamin D research grew exponentially worldwide and was finally visible in Saudi clinical and academic areas. Since then,many landmark studies have been generated with regards to the physiologic functions of vitamin D,both skeletal and extra-skeletal. This review is limited to the prevalence,distribution A systematic review on the prevalence studies done in KSA from 2011 to 2016 was done and revealed that the prevalence of vitamin D deficiency (<50nmol/l) in Saudi Arabia among different populations (adults,children and adolescents,newborns and pregnant/lactating women) is 81.0% (Confidence Interval 95% 68.0–90.0),in line with most neighboring Gulf countries. Vitamin D deficiency in KSA has been mostly associated with bone and insulin-resistant diseases but limited data are available to prove causality. In conclusion,there is a need to develop local consensus guidelines that will identify candidates for screening,monitoring and treating those who are at most risk for vitamin D deficiency complications.



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Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): M.R. Grübler, M. Gaksch, K. Kienreich, N.D. Verheyen, J. Schmid, C. Müllner, G. Richtig, H. Scharnagl, C. Trummer, V. Schwetz, A. Meinitzer, B. Pieske, W. März, A. Tomaschitz, S. Pilz
Background and aimsAccumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension.Methods and resultsThe Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6]ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was −0.004 (95%CI [−0.03 to 0.04]; P=0.819) on ADMA and 0.001 (95%CI [−0.05 to 0.05]; P=0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84–34.9]μmol/L/μmol/L; P=0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70ConclusionsVitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.



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Editorial board

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175





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Developmental vitamin D deficiency and autism: Putative pathogenic mechanisms

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Asad Ali, Xiaoying Cui, Darryl Eyles
Autism is a neurodevelopmental disease that presents in early life. Despite a considerable amount of studies, the neurobiological mechanisms underlying autism remain obscure. Both genetic and environmental factors are involved in the development of autism. Vitamin D deficiency is emerging as a consistently reported risk factor in children. One reason for the prominence now being given to this risk factor is that it would appear to interact with several other epidemiological risk factors for autism. Vitamin D is an active neurosteroid and plays crucial neuroprotective roles in the developing brain. It has important roles in cell proliferation and differentiation, immunomodulation, regulation of neurotransmission and steroidogenesis. Animal studies have suggested that transient prenatal vitamin D deficiency is associated with altered brain development. Here we review the potential neurobiological mechanisms linking prenatal vitamin D deficiency and autism and also discuss what future research targets must now be addressed.



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The concept of the personal vitamin D response index

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Carsten Carlberg, Afrozul Haq
Humans are able to synthesize vitamin D3 in their skin when exposed to UV-B, but seasonal variations, textile coverage and predominant indoor activities often make supplementation with the compound necessary. There is some dispute on the desired vitamin D status, measured via the serum concentration of the most stable vitamin D3 metabolite, 25-hydroxyvitamin D3, and the respective recommended daily supplementation. A possible answer may be provided by the concept of the personal vitamin D response index describing the efficiency of the molecular response to supplementation with vitamin D. The concept is based on the fact that vitamin D3 activates via its metabolite 1α,25-dihydroxyvitamin D3 the transcription factor vitamin D receptor and thus has a direct effect on the epigenome and transcriptome of many human tissues and cell types. Individuals can be distinguished into high, mid and low responders to vitamin D via measuring vitamin D sensitive molecular parameters, such as changes in the epigenetic status and the respective transcription of genes of mobile immune cells from blood or the level of proteins or metabolites in serum. Thus, we suggest that the need for vitamin D supplementation depends on the vitamin D status in relation to the personal vitamin D response index of an individual rather than on the vitamin D status alone.



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Cognitive changes under memantine according to vitamin D status in Alzheimer patients: An exposed/unexposed cohort pilot study

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Pauline Lemire, Antoine Brangier, Melinda Beaudenon, Guillaume T. Duval, Cedric Annweiler
Memantine is a symptomatic treatment that partially prevents cognitive decline in Alzheimer disease (AD). The neuroprotective effects of memantine and vitamin D may potentiate each other, with benefits for cognition. The objective of this exposed/unexposed pilot study was to determine the cognitive changes among AD patients using memantine according to the presence or absence of vitamin D deficiency (VDD). Fifty-eight AD patients followed in a memory clinic during 6 months between 2009 and 2014 (mean±standard deviation, 82.9±5.0years; 56.9%female) were separated into four groups according to VDD (i.e., serum 25-hydroxyvitamin D≤25nM) at M0 and M6 (i.e., Group 1: no VDD-M0, no VDD-M6; Group 2: VDD-M0, no VDD-M6; Group 3: no VDD-M0, VDD-M6; Group 4: VDD-M0, VDD-M6). The 6-month cognitive change was examined with the Mini-Mental State Examination (MMSE) score in the 4 groups according to the use of memantine. Age, gender, body mass index, IADL score, GDS score, and use of pchychoactive drugs were measured at baseline. We found that participants using memantine had a lower MMSE score at M0 compared to those without memantine (P=0.006). After 6 months of follow-up, there was a memantine-related improvement of the MMSE score only in the participants with VDD-M6. This was significant in Group 3 with no VDD-M0 (P=0.039), but not in Group 4 who already had VDD-M0. Similarly, using memantine was associated with a 6-month improvement of MMSE only in Group 3 in whom VDD appeared during the follow-up (β=8.8, P=0.044). In conclusion, the use of memantine was associated with improved cognitive performance after 6 months of treatment in the presence of VDD at M6. Memantine may prevent the cognitive decline that accompanies the onset of VDD, which prompts to give to AD patients a regimen combining both memantine and vitamin D supplements.



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Vitamin D deficiency and the pathogenesis of Crohn’s disease

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): John H. White
Vitamin D has emerged as a key regulator of innate immune responses to pathogen threat. The hormonal form of vitamin D signals through a nuclear receptor transcription factor and regulates gene transcription. Several papers have shown that vitamin D signaling is active both upstream and downstream of pattern recognition receptors, vanguards of innate immune responses. Crohn's disease (CD) is a relapsing-recurring inflammatory bowel disease (IBD) that arises from dysregulated intestinal innate immunity. Indeed, genetic studies have identified several CD susceptibility markers linked to mechanisms of innate immune responses to infection. Interest in links between vitamin D deficiency and CD has grown substantially, particularly in the last five years. While a number of studies have consistently revealed an association between CD and vitamin D deficiency, recent experimental work has uncovered a compelling mechanistic basis for the contribution of vitamin D deficiency to the pathogenesis of the disease. Moreover, a number of intervention trials have provided generally solid evidence that robust vitamin D supplementation may be of therapeutic benefit to patients with CD. This review summarizes these laboratory and clinical findings.



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Vitamin D and cardiovascular diseases: Causality

Publication date: January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 175
Author(s): Sunil J. Wimalawansa
Vitamin D regulates blood pressure, cardiac functions, and endothelial and smooth muscle cell functions, thus, playing an important role in cardiovascular health. Observational studies report associations between vitamin D deficiency with hypertension and cardiovascular-related deaths. Peer-reviewed papers were examined in several research databases as per the guidelines of the Preferred Reporting Items for Systematic Reviews, using key words that address the relationship between vitamin D and cardiovascular disease. Correlations and interpretations were made considering the risks–benefits, broader evidence, and implications. This review analyzed current knowledge regarding the effects of vitamin D on the cardiovascular system. 1,25(OH)2D and related epigenetic modifications subdue cellular inflammation, improve overall endothelial functions, reduce age-related systolic hypertension and vascular rigidity, and attenuate the actions of the renin–angiotensin–aldosterone system. Most observational and ecological studies support 25(OH)vitamin D having protective effects on the cardiovascular system. However, the association of vitamin D deficiency with cardiovascular diseases is based primarily on observational and ecological studies and thus, is a matter of controversy. Adequately powered, randomized controlled clinical trial data are not available to confirm these associations. Thus, to test the hypothesis that correction of vitamin D deficiency protects the cardiovascular system, well-designed, statistically powered, longer-term clinical trials are needed in persons with vitamin D deficiency. Nevertheless, the available data support that adequate vitamin D supplementation and/or sensible sunlight exposure to achieve optimal vitamin D status are important in the prevention of cardiovascular disease and other chronic diseases.

Graphical abstract

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Cerebral venous collaterals: a new fort for fighting ischemic stroke?

Publication date: Available online 2 December 2017
Source:Progress in Neurobiology
Author(s): Lu-sha Tong, Zhen-ni Guo, Yi-bo Ou, Yan-nan Yu, Xiao-cheng Zhang, Jiping Tang, John H. Zhang, Min Lou
Stroke therapy has entered a new era highlighted by the use of endovascular therapy in addition to intravenous thrombolysis. However, the efficacy of current therapeutic regimens might be reduced by their associated adverse events. For example, over-reperfusion and futile recanalization may lead to large infarct, brain swelling, hemorrhagic complication and neurological deterioration. The traditional pathophysiological understanding on ischemic stroke can hardly address these occurrences. Accumulating evidence suggests that a functional cerebral venous drainage, the major blood reservoir and drainage system in brain, may be as critical as arterial infusion for stroke evolution and clinical sequelae. Further exploration of the multi-faceted function of cerebral venous system may add new implications for stroke outcome prediction and future therapeutic decision-making. In this review, we emphasize the anatomical and functional characteristics of the cerebral venous system and illustrate its necessity in facilitating the arterial infusion and maintaining the cerebral perfusion in the pathological stroke content. We then summarize the recent critical clinical studies that underscore the associations between cerebral venous collateral and outcome of ischemic stroke with advanced imaging techniques. A novel three-level venous system classification is proposed to demonstrate the distinct characteristics of venous collaterals in the setting of ischemic stroke. Finally, we discuss the current directions for assessment of cerebral venous collaterals and provide future challenges and opportunities for therapeutic strategies in the light of these new concepts.



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Discovery of novel scaffolds for γ-secretase modulators without an arylimidazole moiety

Publication date: Available online 2 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ryuichi Sekioka, Eriko Honjo, Shugo Honda, Hideyoshi Fuji, Hiroki Akashiba, Yasuyuki Mitani, Shingo Yamasaki
Gamma-secretase modulators (GSMs) selectively inhibit the production of amyloid-β 42 (Aβ42) and may therefore be useful in the management of Alzheimer's disease. Most heterocyclic GSMs that are not derived from nonsteroidal anti-inflammatory drugs contain an arylimidazole moiety that potentially inhibits cytochrome P450 (CYP) activity. Here, we discovered imidazopyridine derivatives that represent a new class of scaffold for GSMs, which do not have a strongly basic end group such as arylimidazole. High-throughput screening identified 2-methyl-8-[(2-methylbenzyl)oxy]-3-(pyridin-4-yl)imidazo[1,2-a]pyridine (3a), which inhibited the cellular production of Aβ42 (IC50 = 7.1 µM) without changing total production of Aβ. Structural optimization of this series of compounds identified 5-[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]-2-ethylisoindolin-1-one (3m) as a potent inhibitor of Aβ42 (IC50 = 0.39 µM) but not CYP3A4. Further, 3m demonstrated a sustained pharmacokinetic profile in mice and sufficiently penetrated the brain.

Graphical abstract

http://ift.tt/2jCmO91

Studies on interactions of carbazole derivatives with DNA, cell image, and cytotoxicity

Publication date: Available online 2 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Guoyan Hao, Jinyu Sun, Chunying Wei
DNA-binding agents have been considered as an established opportunity for the development of anticancer drugs and DNA fluorescence probes. This work reported the synthesis of two novel carbazole derivatives (1 and 2) and investigated their DNA binding properties, living cell image, and cytotoxicity. The results demonstrated that both compounds presented the higher binding affinity to G-quadruplex than to duplex DNA by means of UV-Vis absorption titration and fluorescent intercalator displacement. Continuous variation analysis indicated that their binding stoichiometries of the compound/G-quadruplex were near 2 except the compound/bcl-2. Circular dichroism spectra showed that both compounds had no influence on the conformation of G-quadruplexes. Fluorescence titrations indicated that 2 had the potential to be a G-quadruplex selective fluorescent probe, while 1 could be used as a fluorescent probe for duplex DNA. Confocal fluorescence images indicated that both compounds could enter the living HepG2 cells, and 1 mainly located in nucleus whereas 2 mainly distributed in cytoplasm. DNase and RNase digest tests indicated that both compounds could enter into the nucleus and interact with duplex DNA, especially, 2 could interact with RNA and/or G-quadruplex DNA. They also exhibited an obvious antiproliferative activity to HepG2 by using MTT assay, with IC50 values of 2.7 and 9.5 μM for 1 and 2, respectively.

Graphical abstract

http://ift.tt/2jD46Oy

Factors Associated with Progression of Barrett’s Esophagus: A Systematic Review and Meta-analysis

Publication date: Available online 2 December 2017
Source:Clinical Gastroenterology and Hepatology
Author(s): Rajesh Krishnamoorthi, Siddharth Singh, Karthik Ragunathan, Kavel Visrodia, Kenneth K. Wang, David A. Katzka, Prasad G. Iyer
Background & AimsEndoscopic surveillance of patients with Barrett's esophagus (BE) is inefficient. Risk stratification of patients might improve the effectiveness of surveillance. We performed a systematic review and meta-analysis to identify factors associated with progression of BE without dysplasia or BE with low-grade dysplasia (LGD) to high-grade dysplasia or esophageal adenocarcinoma.MethodsWe performed a systematic search of databases through May 2016 to identify cohort studies of patients with baseline BE without dysplasia or BE with LGD that reported predictors of progression. Pooled estimates (odds ratios) of associations of age, sex, smoking, alcohol use, obesity, baseline LGD, segment length, and medication use with progression were calculated.ResultsWe identified 20 studies, reporting 1231 events in 74943 patients. The studies associated BE progression with increasing age (12 studies; odds ratio [OR], 1.03; 95% CI, 1.01–1.05), male sex (11 studies; OR, 2.16; 95% CI, 1.84–2.53), ever smoking (current or past, 8 studies; OR, 1.47; 95% CI, 1.09–1.98), and increasing BE segment length (10 studies; OR, 1.25; 95% CI, 1.16–1.36), with a low degree of heterogeneity. LGD was associated with a 4-fold increase in risk of BE progression (11 studies; OR, 4.25; 95% CI, 2.58–7.0). Use of proton pump inhibitors (4 studies; OR, 0.55; 95% CI, 0.32–0.96) or statins (3 studies; OR, 0.48; 95% CI, 0.31–0.73) were associated with lower risk of BE progression. Alcohol use and obesity did not associate with risk of progression.ConclusionIn a systematic review and meta-analysis, we associated older age, male sex, smoking, longer BE segment, and LGD with risk of progression of BE. Individuals with these features should undergo more intensive surveillance or endoscopic therapy. Smoking is a modifiable risk factor for cancer prevention in patients with BE.



http://ift.tt/2AAN7H2

Selected Abstracts from the December Issues of the Journal of Vascular Surgery

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2iaUlXu

Contents

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





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Acknowledgement of Reviewers

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2iaUg68

One year on: Test your knowledge from the previous year

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2jF8cWb

Metformin and Abdominal Aortic Aneurysm

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6
Author(s): Robert J. Hinchliffe




http://ift.tt/2iaUbPS

Editorial Board

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2jCJgPn

Forthcoming Events

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2i7YL1l

Towards a Contrast free Approach at EVAR: a New Look at an Old Tool - CO2 Angiography

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6
Author(s): Arindam Chaudhuri, Ramita Dey




http://ift.tt/2jEc8q7

Spanish Translated Abstracts

Publication date: December 2017
Source:European Journal of Vascular and Endovascular Surgery, Volume 54, Issue 6





http://ift.tt/2i7rYcF

The International Neuropeptide society pages

Publication date: December 2017
Source:Peptides, Volume 98





http://ift.tt/2zJ5jKL

Isolation functional characterization of allatotropin receptor from the cotton bollworm, Helicoverpa armigera

Publication date: Available online 2 December 2017
Source:Peptides
Author(s): Fang Zhang, Jun Wang, Kiran Thakur, Fei Hu, Jian-Guo Zhang, Xing-Fu Jiang, Shi-Hen An, Hongbo Jiang, Li Jiang, Zhao-Jun Wei
Insect allatotropin (AT) plays multi-functions including regulation of juvenile hormone synthesis, growth, development and reproduction. In the present study, the full-length cDNA encoding the AT receptor was cloned from the brain of Helicoverpa armigera (Helar-ATR). The ORF of Helar-ATR exhibited the characteristic seven transmembrane domains of the G protein-coupled receptor (GPCR) and was close to the ATR of Manduca sexta in the phylogenetic tree. The Helar-ATR expressed in vertebrate cell lines can be activated by Helar-AT and each Helar-ATL in a dose-responsive manner, in the following order: Helar-ATLI>Helar-ATLII>Helar-AT>Helar-ATLIII. Helar-ATLI and Helar-ATLII represented the functional ligands to Helar-ATR in vitro, while Helar-AT and Helar-ATLIII behaved as partial agonists. The in vitro functional analysis suggested that the Helar-ATR signal was mainly coupled with elevated levels of Ca²⁺ and independent of cAMP levels. Helar-ATR mRNA in larvae showed the highest level in the brain, followed by the thorax ganglion, abdomen ganglion, fat body and midgut. Helar-ATR mRNA levels in the complex of the brain-thoracic-abdomen ganglion on the 2nd day of the larval stage and during later pupal stages were observed to be relatively higher than in the wandering and early pupal stages.



http://ift.tt/2zGGTle

IFC (editorial board)

Publication date: December 2017
Source:Peptides, Volume 98





http://ift.tt/2nnwM2Y

INC Invertebrate Neuropeptide Award (2017)

Publication date: December 2017
Source:Peptides, Volume 98





http://ift.tt/2zHk4xQ

Gayle & Richard Olson prize pages

Publication date: December 2017
Source:Peptides, Volume 98





http://ift.tt/2nqIAll

Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Jingchao Li, Jianghong Rao, Kanyi Pu
As a new class of organic optical nanomaterials, semiconducting polymer nanoparticles (SPNs) have the advantages of excellent optical properties, high photostability, facile surface functionalization, and are considered to possess good biocompatibility for biomedical applications. This review surveys recent progress made on the design and synthesis of SPNs for molecular imaging and cancer phototherapy. A variety of novel polymer design, chemical modification and nanoengineering strategies have been developed to precisely tune up optoelectronic properties of SPNs to enable fluorescence, chemiluminescence and photoacoustic (PA) imaging in living animals. With these imaging modalities, SPNs have been demonstrated not only to image tissues such as lymph nodes, vascular structure and tumors, but also to detect disease biomarkers such as reactive oxygen species (ROS) and protein sulfenic acid as well as physiological indexes such as pH and blood glucose concentration. The potentials of SPNs in cancer phototherapy including photodynamic and photothermal therapy are also highlighted with recent examples. Future efforts should further expand the use of SPNs in biomedical research and may even move them beyond pre-clinical studies.

Graphical abstract

http://ift.tt/2iyRL1e

Does soft really matter? Differentiation of induced pluripotent stem cells into mesenchymal stromal cells is not influenced by soft hydrogels

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Roman Goetzke, Julia Franzen, Alina Ostrowska, Michael Vogt, Andreas Blaeser, Gerd Klein, Björn Rath, Horst Fischer, Martin Zenke, Wolfgang Wagner
Induced pluripotent stem cells (iPSCs) can be differentiated toward mesenchymal stromal cells (MSCs), but this transition remains incomplete. It has been suggested that matrix elasticity directs cell-fate decisions. Therefore, we followed the hypothesis that differentiation of primary MSCs and generation of iPSC-derived MSCs (iMSCs) is supported by a soft matrix of human platelet lysate (hPL-gel). We demonstrate that this fibrin-based hydrogel supports growth of primary MSCs with pronounced deposition of extracellular matrix, albeit it hardly impacts on gene expression profiles or in vitro differentiation of MSCs. Furthermore, iPSCs can be effectively differentiated toward MSC-like cells on the hydrogel. Unexpectedly, this complex differentiation process is not affected by the substrate: iMSCs generated on tissue culture plastic (TCP) or hPL-gel have the same morphology, immunophenotype, differentiation potential, and gene expression profiles. Moreover, global DNA methylation patterns are essentially identical in iMSCs generated on TCP or hPL-gel, indicating that they are epigenetically alike. Taken together, hPL-gel provides a powerful matrix that supports growth and differentiation of primary MSCs and iMSCs – but this soft hydrogel does not impact on lineage-specific differentiation.



http://ift.tt/2iAeSbG

Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Jinah Jang, Ju Young Park, Ge Gao, Dong-Woo Cho
Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics.



http://ift.tt/2AAb9Sr

Emergence of synthetic mRNA: In vitro synthesis of mRNA and its applications in regenerative medicine

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Hyokyoung Kwon, Minjeong Kim, Yunmi Seo, Yae Seul Moon, Hwa Jeong Lee, Kyuri Lee, Hyukjin Lee
The field of gene therapy has evolved over the past two decades after the first introduction of nucleic acid drugs, such as plasmid DNA (pDNA). With the development of in vitro transcription (IVT) methods, synthetic mRNA has become an emerging class of gene therapy. IVT mRNA has several advantages over conventional pDNA for the expression of target proteins. mRNA does not require nuclear localization to mediate protein translation. The intracellular process for protein expression is much simpler and there is no potential risk of insertion mutagenesis. Having these advantages, the level of protein expression is far enhanced as comparable to that of viral expression systems. This makes IVT mRNA a powerful alternative gene expression system for various applications in regenerative medicine. In this review, we highlight the synthesis and preparation of IVT mRNA and its therapeutic applications. The article includes the design and preparation of IVT mRNA, chemical modification of IVT mRNA, and therapeutic applications of IVT mRNA in cellular reprogramming, stem cell engineering, and protein replacement therapy. Finally, future perspectives and challenges of IVT mRNA are discussed.



http://ift.tt/2iBWqzF

Soft chitosan microbeads scaffold for 3D functional neuronal networks

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Maria Teresa Tedesco, Donatella Di Lisa, Paolo Massobrio, Nicolò Colistra, Mattia Pesce, Tiziano Catelani, Elena Dellacasa, Roberto Raiteri, Sergio Martinoia, Laura Pastorino
The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons represents a pivotal step for the development of brain-on-a-chip experimental models to study neuronal (dys)functions and particularly neuronal connectivity. The use of hydrogel-based scaffolds for 3D cell cultures has been extensively studied in the last years. However, limited work on biomimetic 3D neuronal cultures has been carried out to date. In this respect, here we investigated the use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a microbead based 3D scaffold to be coupled to primary neuronal cells. CHI microbeads were characterized by optical and atomic force microscopies. The cell/scaffold interaction was deeply characterized by transmission electron microscopy and by immunocytochemistry using confocal microscopy. Finally, a preliminary electrophysiological characterization by micro-electrode arrays was carried out.

Graphical abstract

http://ift.tt/2AAWneo

Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis

Publication date: February 2018
Source:Biomaterials, Volume 156
Author(s): Koichiro Hayashi, Shota Yamada, Hikaru Hayashi, Wataru Sakamoto, Toshinobu Yogo
Micro-sized drug-carrier particles accumulate mainly in the lungs and nano-sized particles tend to accumulate in the liver and spleen. Here, we show that micro-particles designed to mimic red blood cells (RBCs) can overcome these limitations. The RBC-MPs created in this study have a unique intra-particle elasticity distribution (IED), enabling them to bend around the central axis of the RBC-like dent, enabling them to pass through pores smaller than their diameter, mechanically behaving as authentic RBCs. In contrast, spherical MPs (SPH-MPs) and RBC-MPs hardened by incorporating a siloxane network (SiO2-RBC-MPs), could not. In addition to the IED, we discovered that the deformability also depends on the shape and average particle elasticity. RBC-MPs did not accumulate in the lungs and the spleen, but were targeted specifically to the liver instead. In contrast, non-RBC-MPs such as SPH-MPs and SiO2-RBC-MPs showed heavy accumulation in the lungs and/or spleen, and were dispersed non-specifically in various organs. Thus, controlling the shape and mechanical properties of RBC-MPs is important for achieving the desired biodistribution. When RBC-MPs were loaded with a (TGF)-β receptor inhibitor, RBC-MPs could treat liver fibrosis without pneumotoxicity.



http://ift.tt/2AAdbSB

Vms1: A Cytosolic CAT-Tailing Antagonist to Protect Mitochondria

Publication date: Available online 1 December 2017
Source:Trends in Cell Biology
Author(s): Stefan G. Kreft, Elke Deuerling
In eukaryotes, a cytosolic ribosome quality control complex recycles erroneously stalled ribosomes and modifies faulty nascent chains by ubiquitination and by C-terminal Ala- and Thr-extension (CAT-tailing). Reported recently in Cell, Izawa et al. identify cytosolic Vms1 (VCP/Cdc48-associated mitochondrial stress-responsive 1) as an inhibitor of CAT-tailing, which prevents mitochondrial dysfunction caused by imported CAT-tailed polypeptides.



http://ift.tt/2iAcodz

Spondyloepiphyseal or spondylometaphyseal dysplasia in ancient Greek art

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2iBvK1E

The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2AC9pZ4

A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2iBvvng

Mesh electronics: a new paradigm for tissue-like brain probes

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Guosong Hong, Xiao Yang, Tao Zhou, Charles M Lieber
Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies.



http://ift.tt/2zXyePu

Building stereotypic connectivity: mechanistic insights into structural plasticity from C. elegans

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Yishi Jin, Yingchuan B Qi
The ability of neurons to modify or remodel their synaptic connectivity is critical for the function of neural circuitry throughout the life of an animal. Understanding the mechanisms underlying neuronal structural changes is central to our knowledge of how the nervous system is shaped for complex behaviors and how it further adapts to developmental and environmental demands. Caenorhabditis elegans provides a powerful model for examining developmental processes and for discovering mechanisms controlling neural plasticity. Recent findings have identified conserved themes underlying neural plasticity in development and under environmental stress.



http://ift.tt/2zU9szD

Influence of technological and municipal wastewaters on vulnerable karst riverine system, Krka River in Croatia

Abstract

Exceptional natural value of karst rivers, as well as their potential as a source of drinking water supply, contributes to the importance of developing strict environmental protection. Although most of its watercourse is proclaimed national park, Krka River is impacted by technological and municipal wastewaters, which are released without proper purification only 2 km upstream of the park border. In order to assess water ecological status of the Krka River, vulnerability of karst ecosystem and potential threat to the Krka National Park, spatial and temporal variability of physico-chemical and microbiological water parameters, as well as concentrations of 25 total dissolved metals/metalloids were evaluated. All parameters indicated deteriorated water quality near the wastewater influences, which was for certain metals and bacterial counts even comparable to other world rivers of technological/rural catchment. Downstream location pointed to purification processes in karst river, although nutrients and conductivity were still in a range below good water quality and Al, Co, Fe, Li, Mn, Ni, Sr, Ti, and Zn levels remained comparable to their levels in the pollution impacted area, especially in autumn, indicating season-dependent processes. Presented data provided background status and identified pollution influences in the karst riverine system which indicated potential risk for protected area and a need for comprehensive water quality assessment.

http://ift.tt/2zWq0ax

Clustering pesticides according to their molecular properties, fate, and effects by considering additional ecotoxicological parameters in the TyPol method

Abstract

Understanding the fate and ecotoxicological effects of pesticides largely depends on their molecular properties. We recently developed "TyPol" (Typology of Pollutants), a classification method of organic compounds based on statistical analyses. It combines several environmental (sorption coefficient, degradation half-life) and one ecotoxicological (bioconcentration factor) parameters, to structural molecular descriptors (number of atoms in the molecule, molecular surface, dipole moment, energy of orbitals, etc.). The present study attempts to extend TyPol to the ecotoxicological effects of pesticides on non-target organisms, based on data analysis from available literature and databases. It revealed that relevant ecotoxicological endpoints for terrestrial organisms (e.g., soil microorganisms, invertebrates) that support a range of ecosystemic services are lacking as compared to aquatic organisms. The availability of ecotoxicological parameters was also lower for chronic than for acute ecotoxicity endpoints. Consequently, seven parameters were included for acute (EC50, LC50) and chronic (NOEC) ecotoxicological effects for one terrestrial (Eisenia sp.) and three aquatic (Daphnia sp., algae, Lemna sp.) organisms. In this new configuration, we used TyPol to classify 50 pesticides into different clusters that gather molecules with similar environmental behaviors and ecotoxicological effects. The classification results evidenced relationships between molecular descriptors, environmental parameters, and the added ecotoxicological endpoints. This proof-of-concept study also showed that TyPol in silico classification can successfully address new scientific questions and be expanded with other parameters of interest.

http://ift.tt/2AQ3u2Q

Indicators of environmental contamination by heavy metals in leaves of Taraxacum officinale in two zones of the metropolitan area of Mexico City

Abstract

The present study was designed to detect the effect of heavy metals in two zones of the Metropolitan Area of Mexico City (MAMC), the Centro de Ciencias de la Atmósfera (CCA), and the Altzomoni station in the Iztaccíhuatl-Popocatépetl National Park. Taraxacum officinale was selected as the indicator organism of responses to atmospheric contamination by heavy metals. Determinations of heavy metals were performed, and total mRNA was extracted to quantify the expression of microRNA398 (miR398), superoxide dismutase 2 (CSD2), and the amounts of free radicals using the bromide of 3-(4,5-dimethylthiazole-2-ilo)-2,5-diphenyltetrazole (MTT) salts reduction assay. Results from the Altzomoni station showed high concentrations of five heavy metals, especially Aluminum, while three heavy metals were identified in the CCA-UNAM zone, most importantly, Vanadium, both in the dry season; miR398 expression presented subtle changes but was greater in the leaves from the stations with higher concentrations of heavy metals. Observations included a significant expression of CSD2, mainly in the dry season in both study zones, where levels were significant with respect to controls (p < 0.05). Reduced MTT was also higher in the dry season than in the rainy season (p < 0.05). In conclusion, the increase in heavy metals on the leaves of Taraxacum officinale induces increased expression of the CSD2 gene and reduced MTT; thus, they can be used as indicators for biomonitoring heavy metal concentrations.

http://ift.tt/2zWMKXH

Repellency potential of essential oils against housefly, Musca domestica L.

Abstract

In present study, the essential oils such as Mentha piperita (mentha oil, M.O), Cymbopogan citratus (lemongrass oil, LG.O), Citrus sinensis (orange oil, O.O), and Eucalyptus globulus (eucalyptus oil, E.O) were evaluated for repellency against housefly (Musca domestica) in a specially designed chamber. Further, to study any synergistic effect, essential oil combinations, i.e., M.O + LG.O, M.O + O.O, and M.O + E.O, were screened at 50:50 and 70:30 ratios. The results showed superior repellency of mentha and mentha + lemongrass (70:30) with RC₉₅ value of 0.009 μl/cm³. The other oils and combinations showed higher values of RC₉₅ (0.010–0.041 μl/cm³). The order of repellency was observed to be mentha = mentha + lemongrass (70:30) > mentha + lemongrass (50:50) = lemongrass = mentha + orange (50:50) = mentha + orange (70:30) > mentha + eucalyptus (70:30) > orange > mentha + eucalyptus (50:50) > eucalyptus. Chemical composition of selected essential oils indicated various monoterpenes as active components for efficient repellency. The essential oil of mentha marked the presence of menthol (38%) and menthone (27%) in major fractions, whereas citral (49%) was found dominating in lemongrass oil. Eucalyptus and orange oils showed the presence of 1,8-cineole (85%), and limonene (87%), respectively, as major components of oils. Further, monoterpenes (menthol and limonene) were also evaluated for repellency against housefly. The data showed 90 ± 5 and 60 ± 5% repellency from menthol and limonene, respectively, after 1 h, indicating the vital role of monoterpenes in overall efficacy of essential oil.

http://ift.tt/2AOYLi8

Accuracy and eligibility of CBCT to digitize dental plaster casts

Abstract

Objectives

Software-based dental planning requires digital casts and oftentimes cone-beam computed tomography (CBCT) radiography. However, buying a dedicated model digitizing device can be expensive and might not be required. The present study aimed to assess whether digital models derived from CBCT and models digitized using a dedicated optical device are of comparable accuracy.

Material and methods

A total of 20 plaster casts were digitized with eight CBCT and five optical model digitizers. Corresponding models were superimposed using six control points and subsequent iterative closest point matching. Median distances were calculated among all registered models. Data were pooled per scanner and model. Boxplots were generated, and the paired t test, a Friedman test, and a post-hoc Nemenyi test were employed for statistical comparison. Results were found significant at p < 0.05.

Results

All CBCT devices allowed the digitization of plaster casts, but failed to reach the accuracy of the dedicated model digitizers (p < 0.001). Median distances between CBCT and optically digitized casts were 0.064 + − 0.005 mm. Qualitative differences among the CBCT systems were detected (χ ² = 78.07, p < 0.001), and one CBCT providing a special plaster cast digitization mode was found superior to the competitors (p < 0.05).

Conclusion

CBCT systems failed to reach the accuracy from optical digitizers, but within the limits of the study, accuracy appeared to be sufficient for digital planning and forensic purposes.

Clinical relevance

Most CBCT systems enabled digitization of plaster casts, and accuracy was found sufficient for digital planning and storage purposes.

http://ift.tt/2zXvVvO