Background: The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4+T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance. Methods: CD4+T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers. CD4+T cells from the 3 groups were compared in terms of their gene expression profile, phenotype and functionally upon activation. Results: Gene expression analysis of transcription factors and signalling proteins, in addition to surface proteins expression and cytokine production, revealed that tolerant recipients possessed fewer Th17 cells and exhibited reduced Th17 responses, relative to patients with chronic rejection or healthy volunteers. Furthermore, impaired TCR signalling and altered cytokine cooperation by monocytes contributed to the development of Th17 cells in tolerant recipients. Conclusions: These data suggest that defective proinflammatory Th17 responses may contribute to the prolonged graft survival and stable graft function, which is observed in tolerant recipients in the absence of immunosuppressive agents. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Τρίτη 12 Σεπτεμβρίου 2017
Urinary CXCL10 chemokine is associated with alloimmune and virus compartment-specific renal allograft inflammation.
Background: Urinary CXCL10 is a promising biomarker for subclinical tubulointerstitial inflammation, but limited data exists regarding its correlation with (micro)vascular inflammation. Furthermore, no study has evaluated whether concomitant serum CXCL10 improves the discrimination for (micro)vascular inflammation. Methods: We investigated whether serum/urinary CXCL10 reflect subclinical inflammation within different renal compartments. Patients (n=107) with 107 surveillance biopsies were classified as: normal histology (n=47), normal histology with BKV or CMV viremia (n=17), moderate-severe tubulointerstitial inflammation (tubulitis >=2, n=18), pure microvascular inflammation (n=15), and isolated v lesions (n=10). Serum and urinary CXCL10 ELISA was performed. An independent validation set was evaluated for urine CXCL10: normal histology (n=14), normal histology with BKV or CMV viremia (n=19), tubulitis >=2 (n=15), pure microvascular inflammation (n=41), and isolated v lesions (n=14). Results: Elevated urinary CXCL10 reflected inflammation within the tubulointerstitial (urinary CXCL10/creatinine 1.23ng/mmol vs. 0.46ng/mmol, p=0.02; AUC 0.69, p=0.001) and microvascular compartments (urinary CXCL10/creatinine 1.72ng/mmol vs. 0.46ng/mmol, p=0.03; AUC 0.69, p=0.02) compared to normal histology. Intriguingly, urinary CXCL10 was predominantly elevated with peritubular capillaritis, but not glomerulitis (p=0.04). Furthermore, urinary CXCL10 corresponded with BKV, but not CMV viremia (p=0.02). These urine CXCL10 findings were confirmed in the independent validation set. Finally, serum CXCL10 was elevated with BKV and CMV viremia but was not associated with microvascular or vascular inflammation (p>=0.19). Conclusions: Urinary CXCL10 reflects subclinical inflammation within the tubulointerstitial and peritubular capillary spaces, but not the vascular/systemic compartments; this was consistent with BKV (tubulointerstitial) and CMV viremia (systemic). Serum CXCL10 was not a useful marker for (micro)vascular inflammation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2fi8C3q
http://ift.tt/2fi8C3q
The role of the neural niche in brain metastasis
Abstract
Cancers with neurologic metastasis are a burdensome affliction. As primary cancer care improves, the incidence of metastatic cancer increases as a result of prolonged survival time. Because of this, advances in the understanding of the mechanisms of metastasis are important for the development of continuing management strategies. Knowing how metastatic tumor cells engage, survive, and proliferate in the central nervous system (CNS) is an important first step in developing treatment paradigms. The neural niche is the soil of the CNS that accommodates tumor cells, is a microenvironment of cell signaling that exists between the tumor cell and the native neural cellular network. Elements of the neural niche have been identified as acquaintances for metastatic tumor growth. As more is known about the neural niche, treatment strategies can be developed to target these networks of metastatic tumor progression.
http://ift.tt/2woXmYS
Design strategies for improved velocity-selective pulse sequences
Source:Magnetic Resonance Imaging, Volume 44
Author(s): Gerald B. Matson
Over the years, a variety of MRI methods have been developed for visualizing or measuring blood flow without the use of contrast agents. One particular class of methods uses flow-encoding gradients associated with an RF pulse sequence to distinguish spins in flowing blood from stationary spins. While a strength of these particular methods is that, in general, they can be tailored to capture a desired range of blood flow, such sequences either do not provide a sharp transition from stationary spins to flowing spins, or else are long, generating relaxation losses and undesirable SAR, and have limited immunity to resonance offsets and to RF inhomogeneity. This article provides design methods for improving these longer RF pulse sequences, especially to provide improved immunity to RF inhomogeneity, and also to improve immunity to resonance offsets, as well as to minimize RF sequence length. These design methods retain the flexibility to capture a desired range of blood flow, with sharp transitions between stationary spins and flowing blood. These improvement strategies are demonstrated through Bloch equations simulations of examples of these new sequences in the presence of blood flow. Examples of improved sequences that should prove suitable for use at 3.0Tesla are presented.
http://ift.tt/2jndxoh
Evaluation of the efficacy and safety of oral isotretinoin versus topical isotretinoin in the treatment of plane warts: a randomized open trial
Abstract
Background
Plane warts are a common therapeutic problem. Our aim was to assess the efficacy and safety of oral versus topical isotretinoin in the treatment of plane warts.
Methods
Forty patients with multiple plane warts were randomized into two groups. Group A was treated with oral isotretinoin capsules in the dose of 0.5 mg/kg/d and Group B with topical isotretinoin 0.05% in gel formulation once daily at night. Treatment was given to the patients for 3 months or until the complete clearance of lesions, whichever was earlier. Patients with complete response were followed up monthly for 4 months to record the relapse rate.
Results
Results were analyzed in 16 patients of Group A and 13 patients of Group B. At the end of 3 months of therapy, 11 (69%) patients in Group A had complete remission whereas five (31%) had partial remission. In Group B, at the end of study, five (38%) patients had complete remission and six (46%) had partial remission, whereas two patients had no remission. The difference was statistically significant between two groups; P < 0.0001. The most common side effect in Group A was cheilitis. In Group B, five patients had to be dropped because they developed severe erythema and scaling.
Conclusion
Oral isotretinoin showed better and earlier response than topical isotretinoin. Oral isotretinoin should definitely be given a trial particularly in cases of multiple facial warts before trying various destructive procedures.
http://ift.tt/2xYEdho
Hydraulic performance and fouling characteristics of a membrane sequencing batch reactor (MSBR) for landfill leachate treatment under various operating conditions
Abstract
This study investigates the hydraulic performance and the fouling characteristics of a bench-scale membrane sequencing batch reactor (MSBR), treating mature landfill leachate under various time-based operating conditions. The MSBR system operated initially under a high-flux condition (Period 1) which resulted in a rapid trans-membrane pressure (TMP) rise due to intense fouling. Following the characterization of Period 1 as super-critical, the system was subsequently operated under a near-critical condition (Period 2). The overall filtration resistance analysis showed that cake layer formation was the dominant fouling mechanism during Period 1, contributing to 85.5% of the total resistance. However, regarding the MSBR operation during Period 2, adsorption was found to also be a dominant fouling mechanism (Days 1 to 47), contributing to 29.1% of the total resistance. Additionally, the irregular total resistance variation, which was observed during the subsequent operation (Days 48 to 75), and the respective filtration resistance analysis suggested also the formation of an initial sludge cake layer on the membrane surface, contributing to the 47.7% of the total resistance.
http://ift.tt/2x0cHm0
DIP2C expression in breast cancer and its clinical significance
Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Jing Li, Jin Liang Ping, Bo Ma, Ying Rong Chen, Li Qin Li
IntroductionThe aim of this study was to investigate DIP2C expression in different subtypes of breast cancer tissues and cell lines and its correlation with clinicopathologic and histopathological features, in an effort to elucidate the DIP2C expression profile in breast cancer and its clinical significance.MethodsHereby, we investigated the DIP2C expression in breast cancer tissues using TMA-IHC method and the DIP2C expression in breast cell lines using quantitative RT-PCR.ResultsDIP2C displayed universal expression, being present in all the breast cancer subtypes. There were more cases that staining weakly in breast cancer tissues (n=79/150, 52.7%) than that in fibroadenomas tissues (n=2/18, 11.1%) and normal tissues (n=2/20, 10.0%) (χ2=21.84, P <0.001). Within different intrinsic subtypes of breast cancer assayed by IHC expression profiles, there were less cases of the strongly staining group in basal-like subtype (n=38/86, 44.2%) and HER-2 subtype (n=6/24, 25.0%) than that in luminal A (14/20, 70%) and luminal B (13/20, 65%) subtypes (χ2=11.77, p=0.008). Furthermore, DIP2C expression was positive correlated with ER (χ2=8.90, p=0.003) and PR expression (χ2=10.94, p=0.001), while negative correlated with EGFR expression (χ2=9.27, p=0.002), in accordance with the results of cell lines with different subtypes. Oncomine database also confirmed that, DIP2C was expressed lower in breast cancer tissues, and could indicate prognosis.Conclusionour data revealed DIP2C expression level decreased in breast cancer, especially in basal-like and HER-2 subtypes, and could be a valuable target for diagnosis on specific subtype of breast cancer.
http://ift.tt/2woJD4j
Overexpression of KIFC1 and its association with spheroid formation in esophageal squamous cell carcinoma
Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Takeharu Imai, Naohide Oue, Yuji Yamamoto, Ryuichi Asai, Naohiro Uraoka, Kazuhiro Sentani, Kazuhiro Yoshida, Wataru Yasui
Esophageal squamous cell carcinoma (ESCC) is one of the most common human cancers. We previously reported that KIFC1 is involved in gastric cancer pathogenesis and that KIFC1 plays an important role in gastric cancer spheroid colony formation. However, the significance of KIFC1 in ESCC has not been examined. In the present study, we analyzed the expression and distribution of KIFC1 in 132 ESCC cases by immunohistochemistry. In contrast to weak or no staining of KIFC1 in non-neoplastic mucosa, ESCC tissue showed stronger, more extensive KIFC1 staining. In total, 95 (72%) of 132 ESCC cases were positive for KIFC1. Immunostaining of ALDH1 was also performed, and KIFC1-positive ESCC cases were significantly frequently found in ALDH1-positive ESCC cases compared with ALDH1-negative ESCC cases. Spheroid colony formation is an effective method to characterize CSCs, thus we analyzed sphere number and size at 15days in ESCC cells downregulated for KIFC1 by siRNA transfection. Both the number and size of sphere from TE-1 cells were significantly reduced in KIFC1 siRNA-transfected TE-1 cells than in negative control siRNA-transfected cells. These results suggest that KIFC1 plays an important role in ESCC pathogenesis.
http://ift.tt/2wZELWI
Epigallocatechin-3-gallate promotes apoptosis and reversal of multidrug resistance in esophageal cancer cells
Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Liang Liu, Yingchao Ju, Jing Wang, Rongmiao Zhou
Evidence for demonstrating the role of the green tea component epigallocatechin-3-gallate (EGCG) in esophageal squamous cell carcinoma cells is limited. In this study, we investigated apoptosis induced by EGCG and the underlying molecular mechanisms in human esophageal squamous cell carcinoma cells. The growth-inhibitory effects of EGCG on esophageal cancer cell (Eca109 and Ec9706) were detected by MTT. Using flow cytometry, we determined the cellular apoptosis, bcl-2, bax and caspase-3 protein expression in Eca109 and Ec9706 cells following treatment with EGCG for 24h. After treatment of Eca109/ABCG2 (an esophageal cancer multidrug resistance cell line) cells with adriamycin (ADM) combined with EGCG for 24h, the cellular apoptosis, mitochondrial membrane potential, ADM concentration in cells and ABCG2 protein expression were detected by flow cytometry. EGCG inhibited the growth of Eca109 and Ec9706 cells in a dose- and time- dependent manner. EGCG induced apoptosis, decreased the bcl-2 protein expression and increased the expression of bax and caspase-3 protein. The rate of apoptosis and ADM concentration in the Eca109/ABCG2 cells following treatment with ADM and EGCG were higher than that with ADM treatment alone, although the mitochondrial membrane potential was significantly lower (P <0.01). EGCG reduced the ABCG2 expression of Eca109/ABCG2 cells. Our data indicated that EGCG inhibited cell growth and induced esophageal cancer cell apoptosis. It reduced the bcl-2 protein expression and increased the bax and caspase-3 protein expression. EGCG reversed multi-drug resistance by reducing ABCG2 expression and increasing the anticancer drug concentration in cancer cells.
http://ift.tt/2wo6JYU
The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome
Publication date: Available online 12 September 2017
Source:Pathology - Research and Practice
Author(s): Fang Liu, Fei Ye, Zongyu Guan, Yi Zhou, Fengjun Ji, Qing Zhang, Jianping Zhang, Tianyi Zhang, Songhua Lu
Tandem PH domain-containing proteins TAPP1 and TAPP2 are adaptor proteins that specifically bind to phosphatidylinositol-3,4-bisphosphate, or PI(3,4)P2, a product of phosphoinositide 3-kinases (PI3K). Although PI3K enzymes have multiple functions in cell biology, including cell migration, the functions of PI (3, 4) P2 and its binding proteins are not well understood. Previously studies found that TAPP2 is highly expressed in primary leukemic B cells that have strong migratory capacity. However, the function and underlying mechanisms of TAPP2 in ESCC remain largely unknown. In the present study, we investigated the level of TAPP2 in human esophageal squamous cell carcinoma (ESCC) tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and western blot analyses. TAPP2 protein level was increased in ESCC tissues compared with corresponding adjacent non-tumor tissues. In vitro experiments showed that under-expression of TAPP2 reduced ESCC cell TE1 migration by wound-healing assays and transwell migration assays, and it was concurrent with the decreased expression of the phosphorylation of AKT. Taken together, these findings suggested that TAPP2 serves as oncogenic gene in ESCC and may serve as a new target for ESCC therapy.
http://ift.tt/2x02aY1
An Integrative Interdisciplinary Perspective on Social Dominance Hierarchies
Publication date: Available online 12 September 2017
Source:Trends in Cognitive Sciences
Author(s): Chen Qu, Romain Ligneul, Jean-Baptiste Van der Henst, Jean-Claude Dreher
In the course of evolution, social dominance has been a strong force shaping the organization of social systems in many species. Individuals with a better ability to represent social dominance relationships and to adapt their behavior accordingly usually achieve better access to resources, hence providing benefits in terms of reproduction, health, and wellbeing. Understanding how and to what extent our brains are affected by social dominance requires interdisciplinary efforts. Here, we integrate findings from social neuroscience, evolutionary biology, and developmental psychology to highlight how social hierarchies are learned and represented in primates. We also review neuropharmacological findings showing how dopamine, serotonin, and testosterone influence social hierarchies and we emphasize their key clinical implications on vulnerabilities to neuropsychiatric disorders.
http://ift.tt/2f3r1UT
Cover Image
The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.
http://ift.tt/2wWsYcJ
Cover Image
The cover image, by Miklos Perenyei et al., is based on the Operative Techniques Use of the self-retaining Alexis ring retractor in transoral robotic surgery, DOI: 10.1002/hed.24882.
http://ift.tt/2wWsYcJ
Noninvasive submental fat reduction using colder cryolipolysis
Summary
Background
Cryolipolysis has shown to significantly reduce localized subcutaneous fat, including submental fat. Temperatures below −11°C have not been used to treat the submental region.
Objective
The purpose of this study was to evaluate safety and efficacy of Cryolipolysis for noninvasive reduction of submental fat using lower temperatures and reduced treatment time.
Methods
A small volume applicator was used to treat 15 subjects, using a noninvasive tissue cooling device (CoolSculpting System, ZELTIQ Aesthetics, Pleasanton, CA, USA) during 45 and 30 minutes at −12 and −15°C, respectively, to induce reduction of submental fat. Two treatments with an interval of 10 weeks were performed. Adverse events were monitored to assess safety. Treated area was evaluated using digital photography, and caliper measurements prior treatment, 10 weeks after first treatment and 12 weeks after second treatment. All patients were also evaluated before and after 12-week postlast treatment by Magnetic Resonance Imaging (MRI).
Results
The mean (SD) reduction measured by skin fold caliper was 33% (3.2 mm [1.7 mm]), (95% CI, 0.2297-0.4236; P=.05), and by MRI, mean (SD) reduction was 1.78 mm (1.157 mm). Independent blinded panel was able to correctly identify 60% of before and after photographs; 12 of 15 subjects (80%) were satisfied or very satisfied with the treatment. Side effects were mild and resolved completely within 10 weeks, except for one hyperpigmentation, which resolved spontaneously within 6 months after last treatment.
Conclusion
Cryolipolysis with colder temperature and reduced treatment time continues to be effective and is safe for noninvasive reduction of the submental fat.
http://ift.tt/2jlHWmO
Noninvasive submental fat reduction using colder cryolipolysis
Summary
Background
Cryolipolysis has shown to significantly reduce localized subcutaneous fat, including submental fat. Temperatures below −11°C have not been used to treat the submental region.
Objective
The purpose of this study was to evaluate safety and efficacy of Cryolipolysis for noninvasive reduction of submental fat using lower temperatures and reduced treatment time.
Methods
A small volume applicator was used to treat 15 subjects, using a noninvasive tissue cooling device (CoolSculpting System, ZELTIQ Aesthetics, Pleasanton, CA, USA) during 45 and 30 minutes at −12 and −15°C, respectively, to induce reduction of submental fat. Two treatments with an interval of 10 weeks were performed. Adverse events were monitored to assess safety. Treated area was evaluated using digital photography, and caliper measurements prior treatment, 10 weeks after first treatment and 12 weeks after second treatment. All patients were also evaluated before and after 12-week postlast treatment by Magnetic Resonance Imaging (MRI).
Results
The mean (SD) reduction measured by skin fold caliper was 33% (3.2 mm [1.7 mm]), (95% CI, 0.2297-0.4236; P=.05), and by MRI, mean (SD) reduction was 1.78 mm (1.157 mm). Independent blinded panel was able to correctly identify 60% of before and after photographs; 12 of 15 subjects (80%) were satisfied or very satisfied with the treatment. Side effects were mild and resolved completely within 10 weeks, except for one hyperpigmentation, which resolved spontaneously within 6 months after last treatment.
Conclusion
Cryolipolysis with colder temperature and reduced treatment time continues to be effective and is safe for noninvasive reduction of the submental fat.
http://ift.tt/2jlHWmO
Cancer-Related Cognitive Changes
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Arash Asher, Kathleen Van Dyk, Sunita K. Patel, Robin Newman, Jessica Engle, Nancy Hutchinson, Lynne Padgett
http://ift.tt/2xYkVsv
External Nasal Neuralgia: an Update
Abstract
Purpose of Review
External nasal neuralgia is a rare syndrome of atypical facial pain for which there is limited reports in the scientific literature. We aim to review diagnosis and provide an update on treatments for this rare condition.
Recent Findings
Etiology has been documented as post-traumatic due to direct trauma to the nose area and in few case reports, idiopathic. Sensory innervation of the nose arises from the ophthalmic and maxillary divisions of the trigeminal nerve. Direct injury to the nerve appears to be the etiology of post-traumatic external nasal neuralgia. Pathophysiology for idiopathic nasal neuralgia is poorly understood but it appears to be of a central etiology given lack of response to intranasal anesthetics. Pain can be episodic with episodes of tingling sensation lasting up to 30 min, two to three times per day, but for some patients it can be constant bruised sensation of mild to moderate pain. Diagnostic workup including magnetic resonance imaging of brain and computerized tomography of the sinuses are usually negative, but there have been few cases of a nasal contact point. Routine blood work including erythrocyte sedimentation rate is negative.
Summary
Treatment for this rare condition is varied with very few patients responding to tricyclic antidepressants, specifically amitriptyline. Another medication used as prevention is pregabalin with good results as well. Most patients respond to nerve blockade with local anesthetic to the external nasal nerve and sphenopalatine ganglion block and radiofrequency ablation. More reports of this condition need to be published in the scientific literature to assist with proper diagnosis and treatment of this condition.
http://ift.tt/2xw6EHA
Exploration of chromen-4-one based scaffold’s potential in Alzheimer’s disease: Design, Synthesis and Biological evaluations
Publication date: Available online 11 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Manjinder Singh, Maninder Kaur, Nirmal Singh, Om Silakari
A novel series of flavonoid based compounds were designed, synthesized and biologically evaluated for Acetylcholinesterase (AChE) inhibitory activity integrated with advanced glycation end products (AGEs) inhibitory and antioxidant ptential. Most of the derivatives inhibited AChE in nanomolar IC50 range along with good AGEs inhibitory and radical scavenging activity. Among them, 7m, strongly inhibited AChE (IC50=5.87 nM) and found to be potent as compared to the reference drug donepezil (IC50=12.7 nM). Its potent inhibitory activity has been justified by docking analysis that revealed its dual binding characteristic with both CAS (catalytic active site) and PAS (peripheral anionic site) of AChE, simultaneously. Additionally, this compound also displayed ability to prevent advanced glycation end products formation (IC50=23.0 µM) with additional radical scavenging property (IC50=37.12 nM). It (7m) also ameliorated scopolamine induced memory deficit in mice employing Morris water maze test. Thus, flavonoids might be the promising lead compounds as potential polyfunctional anti-Alzheimer's agents.
Graphical abstract
http://ift.tt/2xk2AJk
External Nasal Neuralgia: an Update
Abstract
Purpose of Review
External nasal neuralgia is a rare syndrome of atypical facial pain for which there is limited reports in the scientific literature. We aim to review diagnosis and provide an update on treatments for this rare condition.
Recent Findings
Etiology has been documented as post-traumatic due to direct trauma to the nose area and in few case reports, idiopathic. Sensory innervation of the nose arises from the ophthalmic and maxillary divisions of the trigeminal nerve. Direct injury to the nerve appears to be the etiology of post-traumatic external nasal neuralgia. Pathophysiology for idiopathic nasal neuralgia is poorly understood but it appears to be of a central etiology given lack of response to intranasal anesthetics. Pain can be episodic with episodes of tingling sensation lasting up to 30 min, two to three times per day, but for some patients it can be constant bruised sensation of mild to moderate pain. Diagnostic workup including magnetic resonance imaging of brain and computerized tomography of the sinuses are usually negative, but there have been few cases of a nasal contact point. Routine blood work including erythrocyte sedimentation rate is negative.
Summary
Treatment for this rare condition is varied with very few patients responding to tricyclic antidepressants, specifically amitriptyline. Another medication used as prevention is pregabalin with good results as well. Most patients respond to nerve blockade with local anesthetic to the external nasal nerve and sphenopalatine ganglion block and radiofrequency ablation. More reports of this condition need to be published in the scientific literature to assist with proper diagnosis and treatment of this condition.
http://ift.tt/2xw6EHA
Is that disgust I see? Political ideology and biased visual attention
Source:Behavioural Brain Research, Volume 336
Author(s): Benjamin Oosterhoff, Natalie J. Shook, Cameron Ford
Considerable evidence suggests that political liberals and conservatives vary in the way they process and respond to valenced (i.e., negative versus positive) information, with conservatives generally displaying greater negativity biases than liberals. Less is known about whether liberals and conservatives differentially prioritize certain forms of negative information over others. Across two studies using eye-tracking methodology, we examined differences in visual attention to negative scenes and facial expressions based on self-reported political ideology. In Study 1, scenes rated high in fear, disgust, sadness, and neutrality were presented simultaneously. Greater endorsement of socially conservative political attitudes was associated with less attentional engagement (i.e., lower dwell time) of disgust scenes and more attentional engagement toward neutral scenes. Socially conservative political attitudes were not significantly associated with visual attention to fear or sad scenes. In Study 2, images depicting facial expressions of fear, disgust, sadness, and neutrality were presented simultaneously. Greater endorsement of socially conservative political attitudes was associated with greater attentional engagement with facial expressions depicting disgust and less attentional engagement toward neutral faces. Visual attention to fearful or sad faces was not related to social conservatism. Endorsement of economically conservative political attitudes was not consistently associated with biases in visual attention across both studies. These findings support disease-avoidance models and suggest that social conservatism may be rooted within a greater sensitivity to disgust-related information.
http://ift.tt/2wVTeEa
THE USE OF HUNTING AND HERDING SPACES: STABLE ISOTOPE ANALYSIS OF LATE ARCHAIC AND EARLY FORMATIVE CAMELIDS IN THE TULAN TRANSECT (PUNA DE ATACAMA, CHILE)
ABSTRACT
We present the results of analyzing stable carbon and nitrogen isotopes in camelid remains found at the Late Archaic site TU-52 (ca. 5000-3800 BP), the Tarajne Phase site TU-94 and the Early Formative sites TU-54, TU-85 and TU-122 (ca. 3100-2400 BP). All of the sites are located in the Puna de Atacama (Northern Chile) along the 14 km Tulan transect, between the head of Tulan ravine (ca. 3000 m.a.s.l.) and the border of the Salar de Atacama (2317 m.a.s.l.). Our aim is to understand how the space was used by hunter-gatherers and early herders from the beginning of camelid domestication to the consolidation of herding practices. Isotopic analyses were complemented with osteometric data in order to correlate changes in animal size and isotopic values with the initiation of animal husbandry. Isotopic and ostemetric results show less variability of δ13C and δ15N values during the Late Archaic and Tarajne Phase, whereas variability is higher during the Early Formative. We postulate that during the latter period there was more widespread use of hunting and herding spaces along the Tulan ravine, including areas above 3000 m.a.s.l. as result of more consolidated herding practices, while the highlands were used as a complementary space to hold livestock near ritual sites and residential settlements.
http://ift.tt/2xYpxPB
SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance
Many hormones/cytokines are secreted in response to exercise and cytokine signaling may play a pivotal role in the training adaptations. To investigate the importance of cytokine signaling during vertical ladder climbing, a resistance exercise model, we produced mice lacking SOCS3 protein exclusively in steroidogenic factor-1 (SF1) cells (SF1 Socs3 KO mice). SF1 expression is found in steroidogenic cells of the adrenal cortex and gonads, as well as in neurons of the ventromedial nucleus of the hypothalamus. Histological markers of the fetal adrenal zone (or X-zone in rodents) were still present in adult males and postpartum SF1 Socs3 KO females, suggesting a previously unrecognized effect of SOCS3 on the terminal differentiation of the adrenal gland. This change led to a distinct distribution of lipid droplets along the adrenal cortex. Under basal conditions, adult SF1 Socs3 KO mice exhibited similar adrenal weight, and plasma ACTH and corticosterone concentrations. Nonetheless, SF1 Socs3 KO mice exhibited a blunted ACTH-induced corticosterone secretion. The overall metabolic responses induced by resistance training remained unaffected in SF1 Socs3 KO mice, including changes in body adiposity, glucose tolerance and energy expenditure. However, training performance and glucose control during intense resistance exercise were impaired in SF1 Socs3 KO mice. Furthermore, a reduced counter-regulatory response to 2-deoxy-D-glucose was observed in mutant mice. These findings revealed a novel participation of SOCS3 regulating several endocrine and metabolic aspects. Therefore, cytokine signaling in SF1 cells exerts an important role to sustain training performance possibly by promoting the necessary metabolic adjustments during exercise.
http://ift.tt/2wZV31U
Body Weight and Body Mass Index in Patients with End-Stage Cystic Fibrosis Stabilize After the Start of Enteral Tube Feeding
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Francis M. Hollander, Nicole M. de Roos, Gerdien Belle van Meerkerk, Ferdinand Teding van Berkhout, Harry G.M. Heijerman, Ed A. van de Graaf
BackgroundEnteral tube feeding (ETF) is widely used in patients with cystic fibrosis (CF) and end-stage lung disease, but previous studies have been limited to investigating whether ETF improves outcomes in patients with moderately or mildly impaired pulmonary function.ObjectiveThis study investigated body weight, body mass index (BMI; calculated as kg/m2), pulmonary function, and the presence of CF-related diabetes before and after the start of ETF.DesignThis was a retrospective observational study.Participants/settingData from 26 adult patients in an outpatient setting who had end-stage CF (19 women) and had been using ETF for at least 6 months between 2000 and 2014 were analyzed.Main outcome measuresBody weight, BMI, pulmonary function (forced expiratory volume in 1 second as percent of predicted) and incidence of CF-related diabetes from 6 months before to 6 months after starting ETF.Statistical analyses performedTime effects were tested with one-way analysis of variance for data that were normally distributed and the Friedman test for non-parametric data. Correlations were tested with Pearson's r or Spearman's ρ, depending on the distribution of the data.ResultsMean body weight increased by 3.5 kg (95% CI 2.2 to 4.8 kg) after patients started ETF. In women, mean BMI decreased by 0.7 in the 6 months before the start of ETF (P<0.05) and increased by 1.4 in the 6 months thereafter (P<0.05). In men, BMI changes were similar (−0.8 and +1.1), but not statistically significant. Forced expiratory volume in 1 second as percent of predicted significantly decreased in time from a median of 28% to 26% at the start of ETF to 25% after 6 months (P=0.0013), with similar trends in women and men. There was no correlation between changes in weight and lung function. CF-related diabetes was already present in 12 patients and developed in 1 more patient after the start of ETF.ConclusionsETF improved body weight and BMI but not pulmonary function in 26 patients with end-stage CF. Clinical outcomes were similar in women and men, but the sample size of men was too small to determine statistical significance.
http://ift.tt/2eTGQts
Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer
Publication date: Available online 12 September 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Guido Eibl, Zobeida Cruz-Monserrate, Murray Korc, Maxim S. Petrov, Mark O. Goodarzi, William E. Fisher, Aida Habtezion, Aurelia Lugea, Stephen J. Pandol, Phil A. Hart, Dana K. Andersen
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.
http://ift.tt/2eTNWOV
Predictors of epinephrine dispensing and allergy follow-up after emergency department visit for anaphylaxis
National guidelines recommend that patients with anaphylaxis be prescribed an epinephrine auto-injector (EAI) and referred to an allergy/immunology (A/I) specialist.
http://ift.tt/2h2V4sO
Predictors of epinephrine dispensing and allergy follow-up after emergency department visit for anaphylaxis
National guidelines recommend that patients with anaphylaxis be prescribed an epinephrine auto-injector (EAI) and referred to an allergy/immunology (A/I) specialist.
http://ift.tt/2h2V4sO
Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections
Source:Vaccine
Author(s): Zeina G. Khodr, Anna T. Bukowinski, Gia R. Gumbs, Ava Marie S. Conlin
BackgroundTo protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2months of age.MethodsThis retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2months of age.ResultsInfants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2months of age (RR, 0.91; 95% CI, 0.84–0.99), and the risk was 17% lower if vaccination was received between 27 and 36weeks of pregnancy (RR, 0.83; 95% CI, 0.74–0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74–0.98).ConclusionsMaternal Tdap vaccination between 27 and 36weeks of pregnancy was consistently protective against infant ARI in the first 2months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.
http://ift.tt/2wW7FrJ
Functional characterization of candidate antigens of Hyalomma anatolicum and evaluation of its cross-protective efficacy against Rhipicephalus microplus
Source:Vaccine
Author(s): Binod Kumar, H.V. Manjunathachar, Gaurav Nagar, G. Ravikumar, José de la Fuente, B.C. Saravanan, Srikant Ghosh
Hyalomma anatolicum and Rhipicephalus microplus seriously affect dairy animals and immunization of host is considered as a sustainable option for the management of the tick species. Identification and validation of protective molecules are the major challenges in developing a cross-protective vaccine. The subolesin (SUB), calreticulin (CRT) and cathepsin L-like cysteine proteinase (CathL) genes of H. anatolicum were cloned, sequenced and analysed for sequence homology. Both Ha-SUB and Ha-CRT genes showed very high level of homogeneity within the species (97.6–99.4% and 98.2–99.7%) and among the tick species (77.3–99.3% and 85.1–99.7%) while for Ha-CathL the homogeneity was lower among ticks (57.5–89.5%). Besides tick species, both Ha-SUB and Ha- CRT genes showed high level of homogeneity with dipterans (47.2–53.4% and 72.0–74.4%) and nematodes (64.0% by CRT). The level of expression of the conserved genes in different stages of the tick species was studied. The differences in fold change of expression (FCE) of the targeted genes in life stages of tick were not statistically significant except Ha-SUB in eggs and in frustrated females, Ha-CRT in fed male and Ha-CathL in unfed and frustrated females where highest FCE was recorded. The functional properties of the genes were studied by RNAi technology and a significant level of gene suppression (p<0.05) resulted in very low percentage of engorgement of treated ticks viz., 3.7%, 11.1% and 30.0% in Ha-SUB, Ha-CRT and Ha-CathL respectively, in comparison to control was recorded. The recombinant proteins rHa-SUB, rHa-CRT and rHa-CathL encoded by the genes were expressed in prokaryotic expression system. They were evaluated for cross-protective efficacy and found to be respectively, 65.4%, 41.3% and 30.2% protective against H. anatolicum and 54.0%, 37.6% and 22.2%, against R. microplus infestations.
http://ift.tt/2wZ6bux
Pre-clinical toxicology considerations for vaccine development
Source:Vaccine
Author(s): Nabil Al-Humadi
Vaccine development requires pre-clinical toxicology studies, following good laboratory practice (GLP), before first in human (phase I) use. Many factors are critical in the final outcome of any pre-clinical toxicology study. The study design is one of these critical factors and should be carefully planned to avoid any false negative and/or false positive results. Preparation is another most critical factor in a successful study. Major changes in any procedure during the course of study should be avoided by all means. For example, if the protocol specified the tail as the site of blood collection and this procedure was used for the control group at the day of necropsy, this collection site should never be replaced by another site (e.g. foot, eye, or heart) in all other treatment groups. Food restrictions and acute restraint stress affect clinical pathology data and should be avoided in rodents. Institutional Animal Care and Use Committee (IACUC) guidelines for frequent blood collections (weekly, monthly, or at necropsy) in any animal species should be strictly followed. Clinical pathology data will be profoundly affected by any diversion from the recommended volumes. If CO2 is specified in the protocol for anesthesia and/or euthanasia, ensuring enough quantity to use for all groups at necropsy is a very important factor. Using two different anesthetics in any study (e.g. CO2 vs. pentobarbital) may result in false positive or false negative results in clinical chemistry parameters. Quality assurance elements (SOPs, instrument validation, lab certification etc.) affect the data interpretation and the final outcome of any toxicology study. SOPs should be up to date and written clearly. All lab instruments should be validated and all laboratories should be certified.
http://ift.tt/2wW7X1y
Comparison of two control groups for estimation of oral cholera vaccine effectiveness using a case-control study design
Source:Vaccine
Author(s): Molly F. Franke, J. Gregory Jerome, Wilfredo R. Matias, Ralph Ternier, Isabelle J. Hilaire, Jason B. Harris, Louise C. Ivers
BackgroundCase-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls.MethodsFrom October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood.ResultsPrimary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant.ConclusionsOCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations.
http://ift.tt/2wYNKG4
Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth
Publication date: Available online 12 September 2017
Source:Vaccine
Author(s): Paul D. Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors asa breast cancer vaccine could lead to an improved immune response against self-antigens found in breast cancer tumors. Indeed, single injections of the vaccine vectors were able to amplify antigen-specific CD8T cells 4–6-fold over naïve mice, similar to the best published vaccine regimens. Immunization of these mice completely inhibited tumor growth in a foreign antigen environment (LV-ERBB2 in wildtype mice), and it reduced the rate of tumor growth in a self-antigen environment (LV-Lalba in wildtype or LV-ERBB2 in MMTV-huHER2 transgenic). These results show that a single injection with targeted lentiviral vectors can be an effective immunotherapy for breast cancer. Furthermore, they could be combined with other immunotherapeutic regimens to improve outcomes for patients with breast cancer.
Graphical abstract
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Sleep disordered breathing in Bardet-Biedl Syndrome
Bardet-Biedl Syndrome (BBS) is an autosomal recessive ciliopathy, and obesity is among its defining characteristics. Consequently, the incidence of sleep disordered breathing (SDB) in this population is expected to be high. Due to its relative rarity, the nature of SDB in this population is poorly described. The objective of this study was to review a single institutional experience in the assessment and management of SDB in patients with BBS.
http://ift.tt/2jnLF3v
Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats
Abstract
Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g−1. The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration–response curves were generated by exposing endothelium-intact samples to NG-nitro-l-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5 μg/kg) for 15 days induced vascular dysfunction due to oxidative stress and morphological damage and should be considered an important cardiovascular risk factor.
http://ift.tt/2fgNH0U
Aerial application of copper for dothistroma control in New Zealand’s planted forests—effect on stream environments
Abstract
Limited information is available on the risk to aquatic environments from the aerial application of copper fungicides to treat dothistroma needle blight in managed forests. Cuprous oxide was aerially applied to three catchments of Pinus radiata of varying age classes in the central North Island of New Zealand. Copper was monitored in stream water and sediments prior to and for 1 month after application. Copper deposits collected from tracer plates deployed above the water surface along the stream channels within the treated areas at each site ranged from 13 to 406 ppm. Lowest concentrations occurred above small stream channels with dense overhead riparian vegetation. Peak copper concentrations in stream water across the three sites ranged from 28 to 60 μg L−1 and were below the analytical detection limit within hours. Copper concentrations were higher and persisted for longer in stream sediment (range 1.7–6.1 mg kg−1, sampled at two sites only). Copper concentrations in sediments were below environmental guidelines. Copper concentrations in water and sediment indicated a low risk to aquatic organisms based on the exposure times to the concentrations measured in this study.
http://ift.tt/2wVOJt5
Ecotoxicological impact assessment of the brine discharges from a desalination plant in the marine waters of the Algerian west coast, using a multibiomarker approach in a limpet, Patella rustica
Abstract
The aim of our study is to evaluate the impact of Bousfer desalination plant brine discharges on the Algerian west coast, on a natural population of the marine gastropod mollusc Patella rustica. The effects of a chronic exposure to such discharges are complex to understand due to the combined effects of environmental physico-chemical parameters (e.g., high salinity) and different pollutants that can modulate the physiological responses of this species to stress. In this context, we assessed the biological effects in a marine species P. rustica, by a multibiomarker approach that provided information on the health status of organisms in response to such an environmental stress. We measured biomarkers in the whole soft tissues of limpets as indicators of neurotoxicity (AChE activity), oxidative stress (CAT, SOD, GR, and GPx activities), biotransformation (GST), oxidative damage (LPO through TBARS levels), and genotoxicity (CSP 3-like activity). In parallel, hydrological parameters were measured in the Bay of Oran, at four selected sites: site H considered as a "hotspot," located at Bousfer desalination plant; two other sites E and W, at the east and the west of H respectively; finally, site R "reference" located in Madragh, which is considered as a remote clean site. Our analyses revealed that the activities of antioxidant defense enzymes reached the highest levels in P. rustica collected from site H. The activation of antioxidant defense system in these organisms translated the alteration of their status health, reflecting a level of environmental disruption generated by the desalination plant brine discharges and the high salinity in this area. We also observed that the tissues of limpets collected from site H as well as the two other sites, E and W, had undergone molecular damage, confirmed by the high levels of CSP 3-like activity. This damage resulted from chronic exposure to environmental conditions, potentially genotoxic, due to the desalination plant discharges. The present results indicate the adverse impact of brine effluents from desalination plants on marine fauna and suggest the need for a more consistent approach to environmental management of brine discharges.
http://ift.tt/2fhqCv4
Pretreatment of skin using an abrasive skin preparation pad, a microneedling device or iontophoresis improves absorption of methyl aminolevulinate in ex vivo human skin
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Hanan Osman-Ponchet, Alexandre Gaborit, Karine Sevin, Christophe Bianchi, Jean-Michel Linget, Claire E. Wilson, Guy Bouvier
BackgroundPretreatment of skin to remove scales/crusts and roughen the surface is essential to enhance the penetration of topically applied methyl aminolevulinate (MAL) prior to photodynamic therapy and to permit daylight to access all parts of the skin lesions. Numerous procedures of skin preparation are currently available. This study compared the in vitro penetration of MAL into ex vivo human skin pretreated with skin preparation pad abrasion or a microneedling device, and evaluated the effectiveness of an iontophoretic device in delivering MAL into ex vivo human skin.MethodsHuman skin samples, obtained from aesthetic surgeries, were used in this study. The thickness of the skin samples ranged between 1.44–2.87mm. Pretreatment of samples was performed with 10 passages of the Ambu® Unilect™ 2121M (Ambu A/S, Denmark) skin preparation pad, 8 rolling repetitions using the microneedling device Dermaroller® HC 902 (Dermaroller GmbH, Germany), or by an iontophoresis device (Feeligreen SA, France) for 1.5hours. The effect of these pretreatment procedures on the penetration of MAL into the skin was assessed.ResultsPenetration in the total skin, liquid receptor and total penetration was most increased by skin preparation pad treatment, followed by microneedling and iontophoresis. Overall, MAL total penetration was increased up to 103-fold by skin preparation pad treatment, 4-fold by microneedling and 1.8-fold by iontophoresis.ConclusionsAbrasion with skin preparation pad was shown to be superior to microneedling and iontophoresis for increasing MAL penetration in ex vivo human skin.
http://ift.tt/2eTUtcf
Editorial Board
Source:Photodiagnosis and Photodynamic Therapy, Volume 19
http://ift.tt/2vSXArN
Role of the IL-12/IL-35 balance in Sjögren’s syndrome
An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35.
http://ift.tt/2xY7jxx
Mast Cell Chymase Decreases The Severity Of Group B Streptococcus Infections
MCPT4-mediated downregulation of fibronectin via proteolytic cleavage contributes to reduced systemic GBS dissemination and preterm birth rates.
http://ift.tt/2wXVmsl
Mast cell exosomes can suppress allergic reactions by binding to IgE
Neutralizing free IgE would appear to be an important strategy for the treatment of allergic diseases. This article explores a novel anti-IgE agent.
http://ift.tt/2xY7gBR
Alveolar eosinophilia in current smokers with chronic obstructive pulmonary disease in the SPIROMICS cohort
Active smoking in stable COPD subjects significantly increased eosinophil accumulation in the distal airspaces, but not in sputum or peripheral blood. Our findings support the need to investigate this cell-type as a potential driver of COPD symptomatology and progression.
http://ift.tt/2wXDH43
Clinical, Immunological and Genetic Spectrum of 696 Patients with Combined Immunodeficiency
Capsule Summary: In this study of 696 patients with CID, molecular diagnosis was achieved in ∼78% of the patients.
http://ift.tt/2xXQfrC
Estimating Vocal Effort from the Aerodynamics of Labial Fricatives: A Feasibility Study
Vocal effort in loud voice is produced with increased subglottal pressure during vowels and increased supraglottal pressure during consonants. In the paper, our main objective is to check whether it was supported by a parallel increase in the airflow resistance of the laryngeal articulator and of the supralaryngeal articulator, here the lips.
http://ift.tt/2jp5JTd
Reverse Takotsubo Cardiomyopathy and Cardiogenic Shock Associated With Methamphetamine Consumption
Source:The Journal of Emergency Medicine
Author(s): Omar Chehab, Adam Ioannou, Akshat Sawhney, Alexandra Rice, Simon Dubrey
BackgroundReverse Takotsubo cardiomyopathy is characterized by transient myocardial hypokinesia affecting predominantly the basal myocardial wall. It is a rare variant of Takotsubo cardiomyopathy affecting younger patients.Case ReportWe report a case of a young man who having consumed methamphetamines presented with cardiogenic shock and severe left ventricular systolic dysfunction, affecting predominantly the basal segments with sparing of the apex. After inotropic support, the left ventricular ejection fraction improved.Why Should an Emergency Physician Be Aware of This?It is important that emergency physicians are aware of the danger of methamphetamine consumption, and how it can lead to potentially fatal acute cardiac syndromes, including reverse Takotsubo cardiomyopathy and cardiogenic shock.
http://ift.tt/2jlgHc6
Male With Sudden Onset Abdominal Pain
Source:The Journal of Emergency Medicine
Author(s): Erica Simon, Jared Cohen, Brit Long
http://ift.tt/2f4E6NQ
U-47700: A Clinical Review of the Literature
Source:The Journal of Emergency Medicine
Author(s): Kerry Anne Rambaran, Steven W. Fleming, Jie An, Samantha Burkhart, Jakub Furmaga, Kurt C. Kleinschmidt, A. Michael Spiekerman, Saeed K. Alzghari
BackgroundU-47700 is a synthetic opioid developed by The Upjohn Company in the 1970s, which has recently appeared in the news and medical literature due to its toxicity. Currently, there are no clinical trial data assessing the safety of U-47700.ObjectiveTo describe the signs and symptoms of ingestion, laboratory testing, and treatment modalities for U-47700 intoxication.DiscussionWe searched PubMed, Embase, Web of Science, and EBSCO for articles using the term "U-47700" and "47700." The following inclusion criteria were used: had to be in English; full text; must involve humans; must be either a randomized control trial, prospective trial, retrospective analysis, case series, or case report; and must include clinical findings at presentation. We identified and extracted data from relevant articles. Ten relevant articles were included with 16 patients. Patients that died after overdose with U-47700 typically presented to the hospital with pulmonary edema. Patients who survived an overdose presented with decreased mental status and decreased respiratory rate suggestive of an opioid toxidrome. Patients also commonly had tachycardia. Immunoassays failed to identify U-47700, and the identification of U-47700 required the use of chromatographic and spectral techniques.ConclusionWe report the first clinical review of U-47700 intoxication.
http://ift.tt/2jl5HLX
Second generation of familial nonmedullary thyroid carcinoma: a meta-analysis on the clinicopathologic features and prognosis
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Yi-mei Zhou, Han Luo, Ju-xiang Gou, Wan-jun Zhao, Wen-yu Dai, Jingqiang Zhu, Zhi-hui Li
Whether the second generation of parent/offspring type familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive and has worse prognosis than their first generation counterpart is controversial. To evaluate the clinicopathologic features and prognosis of the second generation via a comparison between the two groups, We searched three databases (PubMed, EMBASE and the Cochrane library) to review studies published before November 25, 2016. All original studies comparing the clinicopathologic features and prognosis in the first generation of parent/offspring type FNMTC with its second generation counterpart were included. The Q-test and I2 test were used to evaluate homogeneity and funnel plot with Egger's test was used to evaluate publication bias. 6 studies, including 424 subjects were included. There was significant difference between the first and second generation of parent/offspring type FNMTC in the age of onset (SMD=-1.20, 95% CI: -2.38, -0.03, p=0.045), gender distribution (OR=0.48, 95% CI: 0.25, 0.90, p=0.022) and lymph node metastasis (OR=1.84, 95%CI: 1.16, 2.92, p=0.01), while no significant difference in other variables. Thus we conclude that the second generation of parent/offspring type FNMTC patients is in higher risk than their first generation counterpart. We believe continuous study is needed to confirm the result.
http://ift.tt/2xYlNNY
Association of tibial plateau fracture morphology with ligament disruption in the context of multi-ligament knee injury
Source:Current Problems in Diagnostic Radiology
Author(s): Jack Porrino, Michael L. Richardson, Keegan Hovis, Bruce Twaddle, Albert Gee
BackgroundWe identified common morphologies of tibial plateau fractures that arise with multi-ligament knee injuries (MLKI), and investigated the relationship of the fracture with ligament tears. We also evaluated the correlation of three tibial plateau fracture classification systems (Schatzker, AO, and Duparc).MethodsOver a two-year period, a single orthopaedic surgeon at our institution managed 90 MLKI′s. Images of those knees with a tibial plateau fracture were retrospectively reviewed and classified per Schatzker, AO, and Duparc systems. Correlation among the three systems was evaluated using Spearman non-parametric correlation coefficient. Associations between fracture grading system and ligament tears were estimated using logistic regression. Associations between ligament tears and tibial plateau fracture location (medial versus lateral) were estimated using exact logistic regression.ResultsNineteen of 90 knees suffered tibial plateau fractures. There was reasonable correlation among the three tibial plateau classification systems. Increasing grade under the Schatzker system showed statistically significant associations with MCL (p = 0.056) and PLC (p = 0.035) tears. Increasing grade under the Duparc system showed statistically significant associations with MCL (p = 0.032) and PLC (p = 0.058) tears. PLC tears had a statistically significant association with medial plateau fractures (p = 0.003); odds ratio of 121.1 (95% CI = 2.2, ∞). MCL tears had a statistically significant association with lateral plateau fractures (p = 0.004); odds ratio of 18.4 (95% CI = 2.1, ∞). Although not statistically significant, 8 out of 9 knees with a lateral plateau fracture demonstrated tear of the ACL.ConclusionsAs the grade of designation increases within the Schatzker and Duparc tibial plateau fracture classifications, as does the likelihood of MCL and PLC tear. The majority of tibial plateau fractures that occur in the context of MLKI are either isolated to the medial or lateral tibial plateau. Medial tibial plateau fractures are associated with PLC tears. Lateral tibial plateau fractures are associated with MCL tears, and although not statistically significant in our small sample size, 8 out of 9 knees also demonstrated a tear of the ACL.
http://ift.tt/2xvSeHp
Do Interventions Intended to Increase Female Medical Student Interest in Radiology Work?: Preliminary Findings
Source:Current Problems in Diagnostic Radiology
Author(s): Elizabeth D. Yuan, Joseph Makris, Carolynn M. DeBenedectis
PurposeThe purpose of this study is to share the preliminary findings after initiation of interventions at the medical school level which have been suggested by the literature to increase female medical student interest in radiology at one institution. Additionally, the paper provides discussion of how to better future interventions for increasing female medical student interest.MethodsInterventions to increase medical student exposure to radiology were implemented at the University of Massachusetts Medical School in 2012. Radiology was incorporated into the preclinical curriculum; flexible clinical experiences stressing patient contact were created for early exposure to radiology during 3rd year clerkships; and a 'Women in Radiology′ panel was held to promote visibility of female radiologists. In addition, female radiology faculty became more involved in medical school activities and events.ResultsOur results suggest that early exposure in the preclinical curriculum and patient-centered electives increase overall student interest in radiology but only minimally increase female interest. Simply offering the patient-centered electives is not enough as it resulted in more male student enrollment than female (60% vs. 40%, respectively). Just one event promoting visibility of female radiologists changed female medical student perception of patient contact within radiology by a statistically significant amount. Examination of current UMass faculty radiologists by gender demonstrates that full-time, junior female radiologists – the demographic suggested to have the biggest impact on female medical students – only accounted for 4% of faculty.ConclusionThis article may be informative for radiology departments looking to increase female medical student interest. Required visibility of female radiologists and active publicity of female radiologists from the first preclinical year are likely to have the biggest impact in increasing female medical student interest.
http://ift.tt/2y4lcLJ
Re-introducing the delto-acromial perforator flap: clinical experience and cadaver dissection
Although perforator flaps from the pectoral branch of the thoraco-acromial (TA) axis have been well-described, there are few reports of perforator flaps based on the delto-acromial (DA) branches. We have found a reliable perforator coming off the DA branch of the TA axis, and have named a flap based on this vessel the delto-acromial perforator (DAP) flap. We describe our experience with the DAP flap together with a fresh cadaver anatomical study.
http://ift.tt/2fh7DRa
Development and testing of a decision aid for women considering delayed breast reconstruction
The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR.
http://ift.tt/2xjd77S
Force-activatable biosensor enables single platelet force mapping directly by fluorescence imaging
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Yongliang Wang, Dana N. LeVine, Margaret Gannon, Yuanchang Zhao, Anwesha Sarkar, Bailey Hoch, Xuefeng Wang
Integrin-transmitted cellular forces are critical for platelet adhesion, activation, aggregation and contraction during hemostasis and thrombosis. Measuring and mapping single platelet forces are desired in both research and clinical applications. Conventional force-to-strain based cell traction force microscopies have low resolution which is not ideal for cellular force mapping in small platelets. To enable platelet force mapping with submicron resolution, we developed a force-activatable biosensor named integrative tension sensor (ITS) which directly converts molecular tensions to fluorescent signals, therefore enabling cellular force mapping directly by fluorescence imaging. With ITS, we mapped cellular forces in single platelets at 0.4µm resolution. We found that platelet force distribution has strong polarization which is sensitive to treatment with the anti-platelet drug tirofiban, suggesting that the ITS force map can report anti-platelet drug efficacy. The ITS also calibrated integrin molecular tensions in platelets and revealed two distinct tension levels: 12–54 piconewton (nominal values) tensions generated during platelet adhesion and tensions above 54 piconewton generated during platelet contraction. Overall, the ITS is a powerful biosensor for the study of platelet mechanobiology, and holds great potential in antithrombotic drug development and assessing platelet activity in health and disease.
http://ift.tt/2wYi2su
The imaging spectrum of posterior reversible encephalopathy syndrome: A pictorial review
Publication date: January–February 2018
Source:Clinical Imaging, Volume 47
Author(s): Emily Brady, Neal S. Parikh, Babak B. Navi, Ajay Gupta, Andrew D. Schweitzer
Posterior reversible encephalopathy syndrome (PRES) is characterized by the acute onset of neurologic symptoms (headache, altered mental status, visual changes, seizures) with accompanying vasogenic edema on brain imaging. Risk factors for PRES include infection, uremia, malignancy, autoimmune disorders, the peripartum state and hypertension. PRES is classically described as being posterior (i.e. parieto-occipital) but radiologic variants are increasingly recognized. This pictorial review demonstrates the heterogeneity of the different radiologic presentations of PRES in reference to lesion distribution, hemorrhage, diffusion restriction, contrast enhancement, and other associated findings.
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Primary facial reanimation in head and neck cancer
Facial paralysis (FP) carries profound implications for those afflicted. Apart from the devastating functional impairments, facial nerve paralysis disrupts the innate connection between mimetic muscles and emotions. This can create a barrier to social interactions leading to a decline in quality of life [1].
http://ift.tt/2y4hTUG
A rare tumour of the masseter muscle
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): C.A. Righini, H. Gil, I. Atallah
http://ift.tt/2wZd2FL
Data sharing to serve ethics, transparency and reproducibility of medical science
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, P. Bonfils, R. Garrel, R. Jankowski, A. Karkas, N. Leboulanger, M. Makeieff, C. Righini, C. Vincent, C. Martin
http://ift.tt/2jmE7xO
Inside front cover continued (editorial board members)
Source:Biological Psychology, Volume 127
http://ift.tt/2wYlUcU
On-line action monitoring of response execution: An electrophysiological study
Source:Biological Psychology, Volume 129
Author(s): Cédric Meckler, Laurence Carbonnell, Céline Ramdani, Thierry Hasbroucq, Franck Vidal
In between-hand choice-RT-tasks, small incorrect EMG activations occurring before the correct response ("partial errors") are assumed to reflect the detection, inhibition and correction of erroneous hand selection, revealing the existence of an action monitoring system, acting "on-line".Now, EMG activations of the correctly selected hand muscles, too small to reach the response threshold, may also occur before these hand muscles produce an overt correct response ("partial corrects"). We hypothesized that partial corrects reflect incorrect execution of correctly selected responses. We found 1) that response force was smaller on trials preceding a partial correct trial and 2) that the Error Negativity, a performance sensitive ERP, assumed to reveal "on-line" action monitoring, was larger for partial corrects than for correct trials.This also suggests that the competence of the action monitoring system is not restricted to selection errors but also extends to execution errors.
http://ift.tt/2xY7sB1
Editorial board
Source:Biological Psychology, Volume 127
http://ift.tt/2xYcT30
Enzymes as Key Features in Therapeutic Cell Mimicry
Publication date: Available online 12 September 2017
Source:Advanced Drug Delivery Reviews
Author(s): Fabian Itel, Philipp S. Schattling, Yan Zhang, Brigitte Städler
Cell mimicry is a nature inspired concept that aims to substitute for missing or lost (sub)cellular function. This review focuses on the latest advancements in the use of enzymes in cell mimicry for encapsulated catalysis and artificial motility in synthetic bottom-up assemblies with emphasis on the biological response in cell culture or more rarely in animal models. Entities across the length scale from nano-sized enzyme mimics, sub-micron sized artificial organelles and self-propelled particles (swimmers) to micron-sized artificial cells are discussed. Although the field remains in its infancy, the primary aim of this review is to illustrate the advent of nature-mimicking artificial molecules and assemblies on their way to become a complementary alternative to their role models for diverse biomedical purposes.
Graphical abstract
http://ift.tt/2wogLcq
Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions
Abstract
Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.
http://ift.tt/2xw18os
Complement activation, a threat to pregnancy
Abstract
Pregnancy poses a challenge for the immune systems of placental mammals. As fetal tissues are semi-allogeneic and alloantibodies that commonly develop in the mother, the fetus and the placenta might be subject to complement-mediated immune attack with the potential risk of adverse pregnancy outcomes. Here, I describe how the use of animal models was pivotal in demonstrating that complement inhibition at the fetomaternal interface is essential for a successful pregnancy. Studies in animals also helped the identification of uncontrolled complement activation as a crucial effector in the pathogenesis of recurrent miscarriages, intrauterine growth restriction, preeclampsia, and preterm birth. Clinical studies employing complement biomarkers in plasma and urine showed an association between dysregulation of the complement system and adverse pregnancy outcomes. A better understanding of the role of the complement system in pregnancy complications will allow a rational approach to manipulate its activation as a potential therapeutic strategy with the goal of protecting pregnancies and improving long-term outcomes for mother and child.
http://ift.tt/2ffhHdh
Unresolved and critical issues in autoimmune rheumatic diseases
Source:Autoimmunity Reviews
Author(s): Andrea Doria, Mariele Gatto, Luca Iaccarino, Piercarlo Sarzi-Puttini
http://ift.tt/2ffhGWG
Unresolved and critical issues in autoimmune rheumatic diseases
Source:Autoimmunity Reviews
Author(s): Andrea Doria, Mariele Gatto, Luca Iaccarino, Piercarlo Sarzi-Puttini
http://ift.tt/2ffhGWG
NGS-based analysis of base-substitution signatures created by yeast DNA polymerase eta and zeta on undamaged and abasic DNA templates in vitro
Source:DNA Repair
Author(s): Yizhang Chen, Tomohiko Sugiyama
Translesion synthesis (TLS) is the mechanism in which DNA polymerases (TLS polymerases) bypass unrepaired template damage with high error rates. DNA polymerase η and ζ (Polη and Polζ) are major TLS polymerases that are conserved from yeast to humans. In this study, we quantified frequencies of base-substitutions by yeast Polη and Polζ on undamaged and abasic templates in vitro. For accurate quantification, we used a next generation sequencing (NGS)-based method where DNA products were directly analyzed by parallel sequencing. On undamaged templates, Polη and Polζ showed distinct base-substitution profiles, and the substitution frequencies were differently influenced by the template sequence. The base-substitution frequencies were influenced mainly by the adjacent bases both upstream and downstream of the substitution sites. Thus we present the base-substitution signatures of these polymerases in a three-base format. On templates containing abasic sites, Polη created deletions at the lesion in more than 50% of the TLS products, but the formation of the deletions was suppressed by the presence of Polζ. Polζ and Polη cooperatively facilitated the TLS reaction over an abasic site in vitro, suggesting that these two polymerases can cooperate in efficient and high fidelity TLS.
http://ift.tt/2wUb8ae
Production, identification, and field evaluation of sex pheromone from calling females in Diaphania angustalis (Lepidoptera: Crambidae)
Abstract
Insect sex pheromones play a crucial role in the mate finding and calling behavior of Lepidoptera pests. Currently, little is known about the chemical ecology of Diaphania angustalis Snellen (Lepidoptera: Crambidae), a severe and important defoliator attacking the medicinal plant, Alstonia scholaris. In the present study, the pheromone components of D. angustalis females were investigated using electrophysiological and behavioral methods. Distilled hexane extracts of female pheromone glands were analyzed through electroantennogram (EAG) and gas chromatography-electroantennogram detector (GC-EAD), and the active compounds were identified through gas chromatography-mass spectrometry (GC-MS). Production peak of female sex pheromone occurred on the third day of age at 5 h into the scotophase with the EAG test, and the hexane extracts were attractive to males in the wind tunnel test. GC-EAD analysis of virgin males to gland extracts that were subsequently evaluated showed two active compounds, (E,E)-10,12-hexadecadienal (E10E12-16:Ald) and (E,E)-10,12-hexadecadien-1-ol (E10E12-16:OH), based on comparison of retention time and mass spectrum, with suitable synthetic compounds. Under laboratory conditions, the blend of E10E12-16:Ald and E10E12-16:OH in a ratio of 9:1 elicited a stronger EAG response than other treatments or a single component. In the field, more male moths were captured by traps baited with the mixture of E10E2-16:Ald and E10E2-16:OH in a ratio of 9:1, whereas a mixture of 8:1 and 10:1 also caught males. Accordingly, E10E2-16:Ald and E10E2-16:OH were regarded as the major sex pheromone components in D. angustalis females.
http://ift.tt/2w57UAX
Relevance of the Implementation of Teeth in Three-Dimensional Vocal Tract Models
Purpose
Recently, efforts have been made to investigate the vocal tract using magnetic resonance imaging (MRI). Due to technical limitations, teeth were omitted in many previous studies on vocal tract acoustics. However, the knowledge of how teeth influence vocal tract acoustics might be important in order to estimate the necessity of implementing teeth in vocal tract models. The aim of this study was therefore to estimate the effect of teeth on vocal tract acoustics. Method
The acoustic properties of 18 solid (3-dimensional printed) vocal tract models without teeth were compared to the same 18 models including teeth in terms of resonance frequencies (f Rn). The f Rn were obtained from the transfer functions of these models excited by white noise at the glottis level. The models were derived from MRI data of 2 trained singers performing 3 different vowel conditions (/i/, /a/, and /u/) in speech and low-pitched and high-pitched singing. Results
Depending on the oral configuration, models exhibiting side cavities or side branches were characterized by major changes in the transfer function when teeth were implemented via the introduction of pole-zero pairs. Conclusions
To avoid errors in modeling, teeth should be included in 3-dimensional vocal tract models for acoustic evaluation. Supplemental Material
http://ift.tt/2wnkzL9http://article/doi/10.1044/2017_JSLHR-S-16-0395/2654188/Relevance-of-the-Implementation-of-Teeth-in
Myofascial Release or Myofascial Induction ?
Publication date: Available online 12 September 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Leon Chaitow
http://ift.tt/2y3GFUW
Zn(II), Cd(II) and Hg(II) metal complexes of 2-aminonicotinaldehyde: Synthesis, crystal structure, biological evaluation and molecular docking study
Publication date: 1 January 2018
Source:Inorganica Chimica Acta, Volume 469
Author(s): Ramachary Mallela, Ramaiah Konakanchi, Ramu Guda, Nethaji Munirathinam, Durgaiah Gandamalla, Narsimha Reddy Yellu, Laxma Reddy Kotha
In this report, the ligand, 2-aminonicotinaldehyde (ANA) and its metal complexes [Zn(ANA)2Cl2], [Cd(ANA)2Cl2] and [Hg(ANA)2Cl2] have been synthesized and characterized by analytical and various spectroscopic (IR, Electronic, 1H and 13C NMR) studies. The single crystal X-ray diffraction studies of ANA and [Zn(ANA)2Cl2] complex have been discussed. It was found that intra/intermolecular hydrogen bonding exists in both compounds and N-atom of pyridine ring of ANA coordinated to the metal ion in tetrahedral fashion. Metal chlorides, ANA and its complexes were subjected to biological screening, antioxidant, in vitro cytotoxicity and EGFR (Epidermal growth factor receptor) targeting molecular docking studies which indicated the synergistic effect of metal complexes on the biological activity than the free ligand and metal chlorides.
Graphical abstract
http://ift.tt/2f261xK
The Pyk2/MCU Pathway in the Rat Middle Cerebral Artery Occlusion Model of Ischemic Stroke
Source:Neuroscience Research
Author(s): Kun Zhang, Jiajia Yan, Liang Wang, Xinying Tian, Tong Zhang, Li Guo, Bin Li, Wang Wang, Xiaoyun Liu
Mitochondrial dysfunction caused by Ca2+ overload plays an important role in ischemia-induced brain damage. Mitochondrial calcium uniporter (MCU), located on the mitochondrial inner membrane, is the major channel responsible for mitochondrial Ca2+ uptake. Activated proline-rich tyrosine kinase 2 (Pyk2) can directly phosphorylate MCU, which enhances mitochondrial Ca2+ uptake in cardiomyocytes. It has been suggested that the Pyk2/MCU pathway may be a novel therapeutic target in stress-induced cellular apoptosis. In this study, we explored the role of the Pyk2/MCU pathway in the ischemic brain following a stroke injury. We found that the Pyk2/MCU pathway is activated in a rat cerebral ischemia model, and is responsible for mitochondrial dysfunction and neuronal apoptosis. Inhibiting the Pyk2/MCU pathway with a Pyk2 inhibitor (PF-431396) prevented mitochondrial Ca2+ overload, mitochondrial injury, proapoptotic protein release, and cell death. Interestingly, human urinary kallidinogenase (HUK) alleviated neuronal ischemic injury by inhibiting the Pyk2/MCU pathway, suggesting that the Pyk2/MCU pathway may be a protective target for ischemic stroke treatment.
http://ift.tt/2wYYJ4d
Receptive field properties of cat perigeniculate neurons correlate with excitatory and inhibitory connectivity to LGN relay neurons
Source:Neuroscience Research
Author(s): Hironobu Osaki, Tomoyuki Naito, Shogo Soma, Hiromichi Sato
The cat perigeniculate nucleus (PGN) is a visual sector of the thalamic reticular nucleus that consists of GABAergic neurons. It receives excitatory axon-collateral input from relay neurons of the dorsal lateral geniculate nucleus (LGN) to which it provides inhibitory input. Thus, it is usually argued that the PGN works as feedback inhibition to the LGN. At the single neuron level, however, this circuit can also provide lateral inhibition. Which inhibition dominates in the visual circuit of the thalamus has yet to be well characterized. In this study, we conducted cross-correlation analysis of single spike trains simultaneously recorded from PGN and LGN neurons in anesthetized cats. For 12 pairs of functionally connected PGN and LGN neurons with overlapped receptive fields (RF), we quantitatively compared RF properties including the spatial frequency (SF) and temporal frequency (TF) tunings of each neuron. We found the SF and TF tunings of PGN neurons and LGN neurons were similar when there was only excitatory input from the LGN neuron to the PGN neuron, but different when the PGN neuron returned inhibitory inputs back, suggesting the circuit between PGN and LGN neurons works as lateral inhibition for these properties.
http://ift.tt/2jjQBWQ
Activity changes in the left superior temporal sulcus reflect the effects of childcare training on young female students’ perceptions of infants’ negative facial expressions
Source:Neuroscience Research
Author(s): Ayahito Ito, Katsuko Niwano, Motoko Tanabe, Yosuke Sato, Toshikatsu Fujii
In many developed countries, the number of infants who experience non-parent childcare is increasing, and the role of preschool teachers is becoming more important. However, little attention has been paid to the effects of childcare training on students who are studying to become preschool teachers. We used functional magnetic resonance imaging (fMRI) to investigate whether and how childcare training affects brain responses to infants' facial expressions among young females studying to become preschool teachers. Twenty-seven subjects who attended a childcare training session (i.e., the experimental group) and 28 subjects who did not attend the training (i.e., the control group) participated in this study. The participants went through fMRI scanning twice: before and after the childcare training session. They were presented with happy, neutral, and sad infant faces one by one during fMRI scanning. The present neuroimaging results revealed that the activity patterns of the left superior temporal sulcus (STS) for sad faces were modulated by the interaction between the time point of the data collection and group differences. The present results are the first to highlight the effects of childcare training on the human brain.
http://ift.tt/2wYQEw0
When LMO1 Meets MYCN, Neuroblastoma Is Metastatic
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Zhihui Liu, Carol J. Thiele
LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metastatic disease progression.
Teaser
LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metastatic disease progression.http://ift.tt/2xY11Oq
Leukemic Cells “Gas Up” Leaky Bone Marrow Blood Vessels
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Tomer Itkin, Shahin Rafii
In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment.
Teaser
In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment.http://ift.tt/2jlrF1u
Smoke-Induced Changes to the Epigenome Provide Fertile Ground for Oncogenic Mutation
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Susan J. Clark, Peter L. Molloy
How genetic and epigenetic events synergize to generate the oncogenic state is not well understood. In this issue of Cancer Cell, Vaz et al. provide compelling evidence that exposure to chronic cigarette smoke causes progressive epigenetic alterations that prime for key genetic events to drive the development of lung cancer.
Teaser
How genetic and epigenetic events synergize to generate the oncogenic state is not well understood. In this issue of Cancer Cell, Vaz et al. provide compelling evidence that exposure to chronic cigarette smoke causes progressive epigenetic alterations that prime for key genetic events to drive the development of lung cancer.http://ift.tt/2xXIEsP
No Oxygen? No Glucose? No Problem: Fatty Acid Catabolism Enhances Effector CD8+ TILs
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Will Bailis, Justin A. Shyer, Michael Chiorazzi, Richard A. Flavell
The tumor microenvironment presents metabolic constraints to immunosurveiling cells. In this issue of Cancer Cell, Zhang et al. demonstrate that CD8+ TILs reprogram under hypoxic and hypoglycemic conditions, regaining effector function by engaging fatty acid catabolism, which is promoted by fenofibrate and synergistic with immune checkpoint blockade therapy.
Teaser
The tumor microenvironment presents metabolic constraints to immunosurveiling cells. In this issue of Cancer Cell, Zhang et al. demonstrate that CD8+ TILs reprogram under hypoxic and hypoglycemic conditions, regaining effector function by engaging fatty acid catabolism, which is promoted by fenofibrate and synergistic with immune checkpoint blockade therapy.http://ift.tt/2xXM1Qz
Intravascular Survival and Extravasation of Tumor Cells
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Boris Strilic, Stefan Offermanns
Most metastasizing tumor cells reach distant sites by entering the circulatory system. Within the bloodstream, they are exposed to severe stress due to loss of adhesion to extracellular matrix, hemodynamic shear forces, and attacks of the immune system, and only a few cells manage to extravasate and to form metastases. We review the current understanding of the cellular and molecular mechanisms that allow tumor cells to survive in the intravascular environment and that mediate and promote tumor cell extravasation. As these processes are critical for the metastatic spread of tumor cells, we discuss implications for potential therapeutic approaches and future research.
Teaser
Most metastasizing tumor cells reach distant sites by entering the circulatory system. Within the bloodstream, they are exposed to severe stress due to loss of adhesion to extracellular matrix, hemodynamic shear forces, and attacks of the immune system, and only a few cells manage to extravasate and to form metastases. We review the current understanding of the cellular and molecular mechanisms that allow tumor cells to survive in the intravascular environment and that mediate and promote tumor cell extravasation. As these processes are critical for the metastatic spread of tumor cells, we discuss implications for potential therapeutic approaches and future research.http://ift.tt/2jlZteE
Scratching the Surface of Immunotherapeutic Targets in Neuroblastoma
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Clare F. Malone, Kimberly Stegmaier
In this issue of Cancer Cell, Bosse et al. report GPC2 as a therapeutic target in neuroblastoma. They show that GPC2 is selectively expressed on the cell surface of neuroblastoma and is a dependency in this disease. Moreover, they demonstrate the therapeutic potential of an antibody-drug conjugate targeting GPC2.
Teaser
In this issue of Cancer Cell, Bosse et al. report GPC2 as a therapeutic target in neuroblastoma. They show that GPC2 is selectively expressed on the cell surface of neuroblastoma and is a dependency in this disease. Moreover, they demonstrate the therapeutic potential of an antibody-drug conjugate targeting GPC2.http://ift.tt/2xXLvlB
Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Kristopher R. Bosse, Pichai Raman, Zhongyu Zhu, Maria Lane, Daniel Martinez, Sabine Heitzeneder, Komal S. Rathi, Nathan M. Kendsersky, Michael Randall, Laura Donovan, Sorana Morrissy, Robyn T. Sussman, Doncho V. Zhelev, Yang Feng, Yanping Wang, Jennifer Hwang, Gonzalo Lopez, Jo Lynne Harenza, Jun S. Wei, Bruce Pawel, Tricia Bhatti, Mariarita Santi, Arupa Ganguly, Javed Khan, Marco A. Marra, Michael D. Taylor, Dimiter S. Dimitrov, Crystal L. Mackall, John M. Maris
We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target.
Graphical abstract
Teaser
Bosse et al. show that GPC2 is expressed at high levels on most neuroblastomas (NB) but not at appreciable levels in normal childhood tissues and that GPC2 is critical for NB maintenance. They develop a GPC2-directed antibody-drug conjugate that is cytotoxic to GPC2-expressing NB cells in vitro and in vivo.http://ift.tt/2jmzaF5
A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development
Publication date: 11 September 2017
Source:Cancer Cell, Volume 32, Issue 3
Author(s): Yannick Boege, Mohsen Malehmir, Marc E. Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K. Ahuja, Friederike Böhm, Joachim C. Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J. Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M. Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J. Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A. Luther, Philipp J. Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R. Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
Teaser
Boege et al. identify persistent hepatocyte apoptosis as a determinant of hepatocellular carcinoma development. They show that caspase-8 not only executes hepatocyte apoptosis but also has a non-apoptotic role in proliferation-associated DNA damage response mediated by a caspase-8/RIPK1/FADD/c-FLIP complex.http://ift.tt/2jmyU95
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