Brain activations supporting linking of action phases in a sequential manual task

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Daniel Säfström, Erik Domellöf
Most everyday manual tasks, like grabbing a cup of coffee to drink, are comprised of a sequence of action phases. Efficient phase transitions, or linking, are achieved using a predictive control policy where motor commands for the next phase are specified and released in anticipation of sensory confirmation of goal completion of the current phase. If there is a discrepancy between predicted and actual sensory feedback about goal completion, corrective actions are employed to complete the current action phase before proceeding to the next. However, we lack understanding about brain activations supporting such predictive linking and corrective actions in manual tasks. In this study, during 3-T MRI-scanning, sixteen participants (5 males, 11 females; mean age 27.3 years, range 23–37) performed a sequential manual task, with or without the possibility for predictive linking. We found that predictive linking of action phases was associated with increased activation in a network that included right-sided fronto-parietal areas related to visuospatial attention, eye movements and motor planning, left-sided parietal areas related to implicit timing and shifts of motor attention, occipital regions bilaterally reflecting visual processing related to the attended next target, and finally, the anterior midcingulate cortex involved in continuous performance monitoring. Corrective actions were associated with increased activation in the left dorsolateral prefrontal cortex involved in reestablishing executive control over previously automatized behavior.



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Integration of visual and non-visual self-motion cues during voluntary head movements in the human brain

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Andreas Schindler, Andreas Bartels
Our phenomenological experience of the stable world is maintained by continuous integration of visual self-motion with extra-retinal signals. However, due to conventional constraints of fMRI acquisition in humans, neural responses to visuo-vestibular integration have only been studied using artificial stimuli, in the absence of voluntary head-motion. We here circumvented these limitations and let participants to move their heads during scanning. The slow dynamics of the BOLD signal allowed us to acquire neural signal related to head motion after the observer's head was stabilized by inflatable aircushions. Visual stimuli were presented on head-fixed display goggles and updated in real time as a function of head-motion that was tracked using an external camera. Two conditions simulated forward translation of the participant. During physical head rotation, the congruent condition simulated a stable world, whereas the incongruent condition added arbitrary lateral motion. Importantly, both conditions were precisely matched in visual properties and head-rotation. By comparing congruent with incongruent conditions we found evidence consistent with the multi-modal integration of visual cues with head motion into a coherent "stable world" percept in the parietal operculum and in an anterior part of parieto-insular cortex (aPIC). In the visual motion network, human regions MST, a dorsal part of VIP, the cingulate sulcus visual area (CSv) and a region in precuneus (Pc) showed differential responses to the same contrast. The results demonstrate for the first time neural multimodal interactions between precisely matched congruent versus incongruent visual and non-visual cues during physical head-movement in the human brain. The methodological approach opens the path to a new class of fMRI studies with unprecedented temporal and spatial control over visuo-vestibular stimulation.



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The macro-structural variability of the human neocortex

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Frithjof Kruggel
The human neocortex shows a considerable individual structural variability. While primary gyri and sulci are found in all normally developed brains and bear clear-cut gross structural descriptions, secondary structures are highly variable and not present in all brains. The blend of common and individual structures poses challenges when comparing structural and functional results from quantitative neuroimaging studies across individuals, and sets limits on the precision of location information much above the spatial resolution of current neuroimaging methods. This work aimed at quantifying structural variability on the neocortex, and at assessing the spatial relationship between regions common to all brains and their individual structural variants. Based on structural MRI data provided as the "900 Subjects Release" of the Human Connectome Project, a data-driven analytic approach was employed here from which the definition of seven cortical "communities" emerged. Apparently, these communities comprise common regions of structural features, while the individual variability is confined within a community. Similarities between the community structure and the state of the brain development at gestation week 32 lead suggest that communities are segregated early. Subdividing the neocortex into communities is suggested as anatomically more meaningful than the traditional lobar structure.



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Argininosuccinate Synthetase-1 (ASS1) Loss in High-Grade Neuroendocrine Carcinomas of the Urinary Bladder: Implications for Targeted Therapy with ADI-PEG 20

Abstract

High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas. In humans, arginine is a semi-essential amino acid and its synthesis enzyme argininosuccinate synthetase (ASS1) represents the rate-limiting step in arginine biosynthesis. Neoplasms that show low to absent ASS1 expression require extracellular arginine for cancer cell survival, and thus can be targeted using arginine-degrading enzymes such as pegylated arginine deiminase (ADI-PEG 20). An initial study by our group of 19 patients demonstrated that a high percentage of SCNEC lack ASS1 expression. Herein, we evaluated an expanded cohort of 74 radical cystectomy patients with HGNEC, including 63 SCNEC, 5 LCNEC, and 6 mixed morphology HGNEC patients. ASS1 expression was assessed through immunohistochemistry. Fifty-eight (of 74, 78%) patients with HGNEC showed absent ASS1 expression, including all patients with LCNEC and mixed morphology (11 of 11, 100%). Ten-year survival from disease-specific death was not statistically significant between ASS1-expressing and ASS1-deficient cases (p = 0.75). Our results show that HGNEC of the bladder may be candidates for arginine deprivation therapy using drugs such as ADI-PEG 20. Further studies are needed to validate these findings and to determine the therapeutic efficacy of such agents.

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Aquagenic pruritus successfully treated with omalizumab

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Association of clinicopathological features of melanoma with total naevus count and a history of dysplastic naevi: a cross-sectional retrospective study within an academic centre

Summary

Background

High naevus count (HNC) (≥ 50 naevi) and presence of dysplastic naevi (DN) are risk factors for malignant melanoma (MM); however, MMs also occur in patients with low naevus count (LNC) (< 50 naevi) and in patients without DN. Little is known about differences between MMs in these groups.

Aim

To characterize the clinicopathological differences between MMs in patients with HNC and those in patients with LNC, with or without biopsy-proven DN.

Methods

This was a cross-sectional retrospective chart review of 281 patients with MM seen between April 2013 and March 2014 at an academic pigmented lesion clinic (Boston, MA, USA).

Results

Patients with LNC MMs were diagnosed at an older age (51 vs. 41 years, P < 0.001, OR = 0.95, 95% CI 0.93–0.97), with more aggressive MM features, including greater Breslow thickness (1.1 vs. 0.8 mm, P = 0.01), more mitoses (2 vs. 1 mitoses/mm², P < 0.001), lower rate of superficial spreading subtype (58 vs. 78%, P < 0.01, OR = 2.57, 95% CI 1.31–5.03) and higher MM stage (P < 0.001), compared to patients with HNC. Patients with DN had similar trends as those in patients with HNC described above, and in addition, were more likely to have a truncal MM (55 vs. 39%, P < 0.01, OR = 1.97, 95% CI 1.22–3.18) with less ulceration (13 vs. 29%, P < 0.01, OR = 0.36, 95% CI 0.19–0.71). Patients without DN were more likely to have a history of a non-MM skin cancer (32 vs. 19%, P = 0.01, OR = 0.49, 95% CI 0.28–0.85) and an amelanotic MM (33 vs 21%, P = 0.03, OR = 0.55, 95% CI 0.31–0.96).

Conclusions

Patients with LNC may develop MMs with more aggressive features at an older age than patients with HNC. A history of biopsy-proven DN reveals distinct MM differences compared to patients without DN.

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Editorial Board

Publication date: March 2018
Source:Dental Materials, Volume 34, Issue 3





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Features of fracture of prosthetic tooth-endocrown constructions by means of acoustic emission analysis

Publication date: March 2018
Source:Dental Materials, Volume 34, Issue 3
Author(s): Valentyn Skalskyi, Valentyn Makeev, Olena Stankevych, Roman Pavlychko
ObjectiveThe study aims at comparing the fracture resistance of different restorative materials used in dental endocrown restorations and respective endocrown restorations under a quasi-static compressive load using acoustic emission (AE) method.MethodsFive restorative materials were used in this study. The restorative materials were manufactured into discs 13mm in diameter and 5mm thick, which were then divided into 5 groups and included into Type 1: Group B: zirconium dioxide (Prettau zirconia); Group C: ceramics (IPS e.max Press); Group D: metal ceramics (GC Initial MC+Nicrallium N2 BCS); Group E: composite resin (Nano Q); Group F: luting cement (RelyX™ U200). Twenty-five extracted human molars were divided into 5 groups and included into Type 2: Group A: control, no restoration; Group BE: restored by zirconium dioxide endocrowns; Group CE: restored by ceramic endocrowns; Group DE: restored by metal ceramic endocrowns; Group EE: restored by composite resin endocrowns. An increasing load was applied to the center of the samples with a hard steel ball until a fracture occurred. The loading rate was 0.12mm/min. An AE system was used to monitor the fracture of the samples. The load corresponding to the first AE event and the final fracture load were used to evaluate the fracture resistance of the restored teeth. The data were analyzed using ANOVA and Tukey's post hot test (α=0.05).ResultsA lower threshold of 220μV was selected to exclude spurious background signals. For the initial fracture load of Type 1 samples, Group F (0.029kN)<Group E (0.039kN)<Group D (0.056kN)<Group C (0.253kN)<Group B (intact). The same trend was found for the final fracture load, i.e., Group F (1.289kN)<Group E (1.735kN)<Group D (3.362kN)<Group C (6.449kN)<Group B (intact). For the initial and final fracture load, statistically significant differences (p<0.05) were found between group C and the others groups. For the initial fracture load of Type 2 samples, Group EE (0.069kN)<Group DE (0.072kN)<Group CE (0.148kN)<Group BE (2.511kN). For the final fracture load, Group EE (1.533kN)<Group CE (2.726kN)<Group BE (3.082 kN)<Group DE (3.320kN). The initial fracture load of the ceramic samples is somewhat higher than that for the endocrown restorations with the endocrowns made of this material (0.253 and 0.148kN, respectively). At the same time, for the metal ceramic and composite resin samples, the initial fracture loads are somewhat lower than in case of compression of the endocrown restorations with the endocrowns made of these materials (0.056 and 0.072kN; 0.039 and 0.069kN, respectively). The final fracture load of all the samples of the dental materials exceeds the strength of the respective endocrown restorations. The final fracture loads of the endocrown restorations with zirconium dioxide and ceramic endocrowns (3.082 and 2.726kN, respectively) are significantly lower than the final fracture load of the respective endocrown materials (intact and 6.449kN, respectively).SignificanceDental restorations should be made of high-strength materials. Zirconia displayed the highest fracture strength, while composite resin had the lowest fracture strength out of the materials used for the endocrowns. For teeth restored with endocrowns, the use of metal ceramics as endocrown material may lower the risk of failure during clinical use.



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Editorial Board

Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5





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Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity

Publication date: Available online 8 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Hidefumi Yoshinaga, Tomoaki Nishida, Izumi Sasaki, Taro Kato, Hitomi Oki, Kazuki Yabuuchi, Tomohiro Toyoda
We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman-4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex.

Graphical abstract

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2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism

Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5
Author(s): Sungjin Ahn, Moonyoung Lee, Seungchan An, Sooyeol Hyun, Jiho Hwang, Jongkook Lee, Minsoo Noh
Adiponectin is a major adipocytokine secreted from mammalian adipocytes. Relatively low expression of adiponectin is associated with various human metabolic diseases and some cancers. Adiponectin-secreting compounds have therapeutic potential for these diseases. Adipogenesis of human bone marrow-mesenchymal stem cells (hBM-MSCs) has been used as a phenotypic assay to find adiponectin secreting compounds. In a phytochemical library screen, 2-formyl-komarovicine, 1-(quinolin-8-yl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carbaldehyde, isolated from Nitraria komarovii was identified as a potential adiponectin-secreting compound. To validate the results of the impure phytochemical, we synthesized 2-formyl-komarovicine. The synthetic 2-formyl-komarovicine significantly promoted adiponectin production during adipogenesis in hBM-MSCs. In a target identification experiment, 2-formyl-komarovicine bound to peroxisome proliferator-activated receptor γ (PPARγ) in a concentration-dependent manner. Notably, 2-formyl-komarovicine competitively inhibited the adiponectin-promoting activity of a full PPARγ agonist, troglitazone, in hBM-MSCs, which is a pharmacological feature of a partial agonist. The ligand-docking model showed that 2-formyl-komarovicine interacted with the hydrophobic pocket of the PPARγ ligand-binding domain, but lacked an interaction to stabilize helix H12, which is one of the major binding themes of PPARγ partial agonists. We concluded that 2-formyl-komarovicine provides a novel pharmacophore for PPARγ partial agonists to increase adiponectin production.

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Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5





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Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5





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Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5





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Design, synthesis, and evaluation of the antiproliferative activity of hydantoin-derived antiandrogen-genistein conjugates

Publication date: Available online 16 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Alex George, Idris Raji, Bekir Cinar, Omer Kucuk, Adegboyega K. Oyelere
Androgen receptor (AR) signaling is vital to the viability of all forms of prostate cancer (PCa). With the goal of investigating the effect of simultaneous inhibition and depletion of AR on viability of PCa cells, we designed, synthesized and characterized the bioactivities of bifunctional agents which incorporate the independent cancer killing properties of an antiandrogen and genistein, and the AR downregulation effect of genistein within a single molecular template. We observed that a representative conjugate, 9b, is much more cytotoxic to both LNCaP and DU145 cells relative to the antiandrogen and genistein building blocks as single agents or their combination. Moreover, conjugate 9b more effectively down regulates cellular AR protein levels relative to genistein and induces S phase cell cycle arrest. The promising bioactivities of these conjugates warrant further investigation.

Graphical abstract

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CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

Publication date: Available online 15 February 2018
Source:Cell Stem Cell
Author(s): Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C. Robson, Paul S. Frenette, Joji Fujisaki
A crucial player in immune regulation, FoxP3⁺ regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence. In transplantation settings, niche Tregs prevented allogeneic (allo-) HSC rejection through adenosine and facilitated allo-HSC engraftment. Furthermore, transfer of niche Tregs promoted allo-HSC engraftment to a much greater extent than transfer of other Tregs. These results identify a unique niche-associated Treg subset and adenosine as regulators of HSC quiescence, abundance, and engraftment, further highlighting their therapeutic utility.

Graphical abstract

Teaser

Hirata et al. identify a regulatory T cell (Treg) population that localizes in the hematopoietic stem cell (HSC) niche with high-level expression of CD150, an HSC marker. These niche-associated Tregs maintain HSC quiescence and immune privilege through adenosine. Furthermore, transfer of niche Tregs significantly improves allogeneic HSC engraftment.


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Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

Publication date: Available online 15 February 2018
Source:Cell Stem Cell
Author(s): Nigel G. Kooreman, Youngkyun Kim, Patricia E. de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P. Brouwer, David T. Paik, Idit Sagiv-Barfi, Arnold Han, Paul H.A. Quax, Jaap F. Hamming, Ronald Levy, Mark M. Davis, Joseph C. Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b⁺GR1^hi myeloid cells. Adoptive transfer of T cells isolated from vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotes an antigen-specific anti-tumor T cell response. Our data suggest an easy, generalizable strategy for multiple types of cancer that could prove highly valuable in clinical immunotherapy.

Graphical abstract

Teaser

Wu and colleagues show that cancer immunity against multiple types of cancer can be achieved using an easily generalizable iPSC-based cancer vaccine. This immunity is based on overlapping epitopes between iPSCs and cancer cells and can also be achieved by reactivating the immune system as an adjuvant immunotherapy.


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Transcriptional Regulation of the Warburg Effect in Cancer by SIX1

Publication date: Available online 15 February 2018
Source:Cancer Cell
Author(s): Ling Li, Yingchun Liang, Lei Kang, Yang Liu, Shan Gao, Siyu Chen, Ying Li, Wenye You, Qian Dong, Tian Hong, Zhifeng Yan, Shuai Jin, Tao Wang, Wei Zhao, Haixing Mai, Jun Huang, Xiao Han, Quanbo Ji, Qi Song, Chao Yang, Shixin Zhao, Xiaojie Xu, Qinong Ye
Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target.

Graphical abstract

Teaser

Li et al. show that transcription factor SIX1 regulates aerobic glycolysis in cancer by binding promoters and recruiting HBO1 and AIB1 to induce the expression of glycolytic genes. SIX1 is negatively regulated by miR-548a-3p, and modulation of components of this pathway affects tumor metabolism and growth.


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Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

Publication date: Available online 15 February 2018
Source:Cancer Cell
Author(s): Ana Costa, Yann Kieffer, Alix Scholer-Dahirel, Floriane Pelon, Brigitte Bourachot, Melissa Cardon, Philemon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andrei Zinovyev, Anne-Marie Givel, Maria-Carla Parrini, Vassili Soumelis, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4⁺CD25⁺ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25^HighFOXP3^High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.

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Teaser

Costa et al. identify four subsets of carcinoma-associated fibroblasts (CAF) in breast cancer. CAF-S1 promotes an immunosuppressive microenvironment by recruiting CD4⁺CD25⁺ T cells, via secreting CXCL12, and promoting their differentiation to Tregs and survival, via expressing T cell interacting proteins.


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Screen for Slit/Robo signaling in trunk neural cells reveals new players

Publication date: June 2018
Source:Gene Expression Patterns, Volume 28
Author(s): Darwin Martinez, Nora Zuhdi, Michelle Reyes, Blanca Ortega, Dion Giovannone, Vivian M. Lee, Maria Elena de Bellard
Slits ligands and their Robo receptors are involved in quite disparate cell signaling pathways that include axon guidance, cell proliferation, cell motility and angiogenesis. Neural crest cells emerge by delamination from neural cells in the dorsal neural tube, and give rise to various components of the peripheral nervous system in vertebrates. It is well established that these cells change from a non-migratory to a highly migratory state allowing them to reach distant regions before they differentiate. However, but the mechanism controlling this delamination and subsequent migration are still not fully understood. The repulsive Slit ligand family members, have been classified also as true tumor suppressor molecules. The present study explored in further detail what possible Slit/Robo signals are at play in the trunk neural cells and neural crest cells by carrying out a microarray after Slit2 gain of function in trunk neural tubes. We found that in addition to molecules known to be downstream of Slit/Robo signaling, there were a large set of molecules known to be important in maintaining cells in non-motile, epithelia phenotype. Furthermore, we found new molecules previously not associated with Slit/Robo signaling: cell proliferation markers, Ankyrins and RAB intracellular transporters. Our findings suggest that neural crest cells use and array of different Slit/Robo pathways during their transformation from non-motile to highly motile cells.



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Editorial Board

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Sonodynamic Therapy Mediated by Emodin Induces the Oxidation of Microtubules to Facilitate the Sonodynamic Effect

Publication date: Available online 15 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Jili Qian, Qianping Gao
In previous studies, sonodynamic therapy mediated by emodin (emodin-SDT) induced cytoskeletal filament disruption and apoptosis of THP-1-derived macrophages. In this research, we investigated the underlying mechanism. THP-1-derived macrophages were incubated with emodin and exposed to ultrasound irradiation. After emodin-SDT, we measured the production of reactive oxygen species (ROS) and analyzed the level of amino acid oxidation in microtubules, the cleavage of microtubules and the mitochondrial membrane potential (MMP). We found that intracellular emodin accumulated mainly on microtubules. After emodin-SDT, generation of ROS was evident. Analysis of the carbonyl content of proteins suggested oxidation of microtubules. Microtubules were disrupted after emodin-SDT, and the antioxidant N-acetyl-L-cysteine prevented this disruption. MMP decreased after emodin-SDT, and this effect could be prevented by N-acetyl-L-cysteine. We conclude that emodin-SDT induces the generation of ROS. The oxidation of microtubules leads to its cleavage and the subsequent decline in MMP.



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Non-invasive vagus nerve stimulation reduces blood-brain barrier disruption in a rat model of ischemic stroke

Publication date: Available online 15 February 2018
Source:Brain Stimulation
Author(s): Yirong Yang, Lisa Y. Yang, Lilla Orban, Darnell Cuylear, Jeffrey Thompson, Bruce Simon, Yi Yang
BackgroundVagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open.HypothesisThis study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain.MethodsSpontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO. nVNS treated rats received 5 stimulations (duration: 2 min; every 10 min) on the skin overlying the cervical vagus nerve in the neck beginning 30 min after MCAO onset. Control rats received the same stimulations on the quadriceps femoris muscle. Twenty-four hours after MCAO onset, MRI and immunohistochemistry (IHC) were performed for analyses of infarct size and BBB leakage.ResultsCompared with the control group, anatomic MRI T2-weighted images showed significantly smaller infarct sizes in the nVNS group. Dynamic contrast-enhanced (DCE)-MRI showed a significantly decreased BBB transfer rate (Ki map) in the lesion area in the nVNS group, which was spatially correlated with the attenuation of the infarct size. Furthermore, significantly lower serum IgG leakage, visualized by IHC, was seen in the ischemic hemisphere in nVNS treated rats. nVNS also protected vascular tight junction proteins from disruption in microvessels, and reduced expression of matrix metalloproteinases-2/9 in reactive astrocytes surrounding the compromised vessels in the ischemic hemispheres.ConclusionOur data suggest that the neuroprotective role of a series of nVNS administrations during MCA occlusion, spatially correlates with protection of BBB integrity from damage and reduction of infarct extent induced by ischemic stroke.



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Ammonia: A novel target for the treatment of Non-Alcoholic Steatohepatitis

Publication date: Available online 15 February 2018
Source:Medical Hypotheses
Author(s): Karen Louise Thomsen, Francesco De Chiara, Krista Rombouts, Hendrik Vilstrup, Fausto Andreola, Rajeshwar P. Mookerjee, Rajiv Jalan
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage. Ammonia has been shown to activate HSCs in vivo and in vitro. Hyperammonemia in the context of NASH may therefore favour the progression of fibrosis and the disease. We therefore hypothesise that ammonia is a potential target for prevention of fibrosis progression of patients with NASH.



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Molecular hypotheses to explain the shared pathways and underlying pathobiological causes in catatonia and in catatonic presentations in neuropychistric disorders

Publication date: Available online 15 February 2018
Source:Medical Hypotheses
Author(s): E.M. Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways). SNORD115 controls five genes CRHR1, PBRM1, TAF1, DPM2, and RALGPS1 as well as the alternative splicing of serotonin 2C receptor. SNORD115 abnormalities with varying downstream multigene involvement would account for catatonia across the life span within some subtypes of autism spectrum disorders, schizophrenia, bipolar and major depressive disorder, psychosis, genetic disorders, and in immune disorders such as anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis as well as the susceptibility to the neuroleptic malignant syndrome (NMS) if environmentally triggered. Furthermore, SNORD115 genes may underlie a genetic vulnerability when environmental triggers result in excess serotonin producing the serotonin syndrome, a condition similar to NMS in which catatonia may occur. Dysfunction of SNORD115-PBRM1 connecting with SMARCA2 as well as other proven schizophrenia-associated genes might explain why traditionally catatonia has been classified with schizophrenia. SNORD115-TAF1 and SNORD-DPM2 dysfunction introduce possible clues to the parkinsonism and increased creatinine phosphokinase in NMS, while abnormalities of SNORD115-RALGPS1 suggest links to both anti-NMDAR encephalitis and the proven predisposing catatonic SHANK3 gene. The second hypothesis postulates that periodic catatonia (PC) on 15q15 involves abnormalities of vacuolar protein sorting 39 (VPS39), a proven de novo schizophrenic gene in this chromosomal locus and part of the HOPS complex. These will impact the autophagic and endocytic pathways, thereby lowering lysosomal degradation. VPS39 mutations may be considered also to disrupt lysosome-mitochondria tethering and transport of lipids and calcium through membrane contact sites (MCSs). To account for the periodicity in PC it is speculated that the mammalian equivalent of the vacuole and mitochondria patch (vCLAMP) would be altered by VPS39 mutations and subsequently followed by the mammalian equivalent of endoplasmic reticulum mitochondria encounter structure (ERMES) restoring mitochondrial homeostasis. Future precision psychiatry will require accurate pathophysiologically- defined psychiatric diagnoses to accelerate the discovery of specific molecular-targeted medications to improve therapeutic outcomes.



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Biocontrol activity of surfactin A purified from Bacillus NH-100 and NH-217 against rice bakanae disease

Publication date: Available online 15 February 2018
Source:Microbiological Research
Author(s): Ambrin Sarwar, Muhammad Nadeem Hassan, Muhammad Imran, Mazhar Iqbal, Saima Majeed, Günter Brader, Angela Sessitsch, Fauzia Yusuf Hafeez
The potential of the Bacillus genus to antagonize phytopathogens is associated with the production of cyclic lipopeptides. Depending upon the type of lipopeptide, they may serve as biocontrol agents that are eco-friendly alternatives to chemical fertilizers. This study evaluates the biocontrol activity of surfactin-producing Bacillus (SPB) strains NH-100 and NH-217 and purified surfactin A from these strains against rice bakanae disease. Biologically active surfactin fractions were purified by HPLC, and surfactin A variants with chain lengths from C12 to C16 were confirmed by LCMS-ESI. In hemolytic assays, a positive correlation between surfactin A production and halo zone formation was observed. The purified surfactin A had strong antifungal activity against Fusarium oxysporum, F. moniliforme, F. solani, Trichoderma atroviride and T. reesei. Maximum fungal growth suppression (84%) was recorded at 2000 ppm against F. moniliforme. Surfactin A retained antifungal activity at different pH levels (5–9) and temperatures (20, 50 and 121 °C). Hydroponic and pot experiments were conducted to determine the biocontrol activity of SPB strains and the purified surfactin A from these strains on Super Basmati rice. Surfactin production in the rice rhizosphere was detected by LCMS-ESI at early growth stages in hydroponics experiments inoculated with SPB strains. However, the maximum yield was observed with a consortium of SPB strains (T4) and purified surfactin A (T5) treatments in the pot experiment. The outcomes of the present study revealed that surfactin A significantly reduced rice bakanae disease by up to 80%. These findings suggest that purified surfactin A could be an effective biocontrol agent against bakanae disease in rice and should be incorporated into strategies for disease management.



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Editorial Board and Contents

Publication date: March 2018
Source:Trends in Cell Biology, Volume 28, Issue 3





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Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna

Publication date: Available online 15 February 2018
Source:Biomedicine & Pharmacotherapy
Author(s): Naeem Ullah Jan, Amjad Ali, Bashir Ahmad, Naveed Iqbal, Achyut Adhikari, Inayat-ur-Rehman, Abid Ali, Safdar Ali, Azra Jahan, Hamid Ali, Ijaz Ali, Anwar Ullah, Syed Ghulam Musharraf
The demand for natural medicines has increased because of their limited adverse effects. The aim of study is to explore the antidiabetic potential of isolated steroidal alkaloid from Sarcococca saligna in streptozotocin induced diabetic rats. To determine the antidiabetic activity of steroidal alkaloids, diabetes was induced in rats by injecting streptozotocin intraperitoneally at a dose of 40 mg/Kg. After a week of STZ injection the treatment were started and the 8th day was considered as the 1st day of treatment and up to four weeks the rats were treated with steroidal alkaloids. Animals were divided into five groups, group 1 considered as a control group by receiving normal saline (1 ml/Kg) twice daily and group 2, 3, 4 were treated with active compound sarcovagine-D, saracodine and holaphylline at the dose of 5 mg/Kg subcutaneously twice a day while group 5 was treated with a standard drug glibenclamide at a dose of 1 mg/Kg/day. The result showed that treated group 2 and 4 reduced the glucose level in blood significantly while group 3 showed moderate glucose reduction. The fructosamine level reduced significantly in treating group 4 from the 2nd week of treatment while group 2 and 3 decreased the level significantly in week 4 in diabetic rats. The treated groups showed gradual decreases the glucose level in 1st and 2nd week of oral glucose tolerance test compared to control group. The group receiving holaphylline (4) and sarcovagine-D (2) showed good improvements in blood lipids while the effect of compound on body weight showed less significant improvement. The present study concluded that steroid alkaloids from isolated Sarcococca saligna possess hypoglycemic effect and improve others diabetes associated complications. Together these finding further research is needed using a range of doses to explore the other possible beneficial effects in diabetes mellitus and its molecular mechanism.



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An aligned porous electrospun fibrous membrane with controlled drug delivery- an efficient strategy to accelerate diabetic wound healing with improved angiogenesis

Publication date: Available online 15 February 2018
Source:Acta Biomaterialia
Author(s): Xiaozhi Ren, Yiming Han, Jie Wang, Yuqi Jiang, Zhengfang Yi, He Xu, Qinfei Ke
A chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure. The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge. Herein, we reported a kind of aligned porous poly (L-lactic acid) (PLLA) electrospun fibrous membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS) for diabetic wound healing. The PLLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers, while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers. The in vitro results revealed that the aligned porous composite membranes (DS-PL) could stimulate the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) compared with the pure PLLA membranes. The in vivo study further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization, re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed, which eventually stimulated the healing of the diabetic wound. Collectively, these results suggest that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable released DMOG drugs as well as Si ions from the membranes, which could create a synergetic effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a potential novel therapeutic strategy for highly efficient diabetic wound healing.

Graphical abstract

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Nanofibrous PLGA Electrospun Scaffolds Modified with Type I Collagen Influence Hepatocyte Function and Support Viability In Vitro

Publication date: Available online 15 February 2018
Source:Acta Biomaterialia
Author(s): Jessica H. Brown, Prativa Das, Michael D. DiVito, David Ivancic, Lay Poh Tan, Jason A. Wertheim
A major challenge of maintaining primary hepatocytes in vitro is progressive loss of hepatocyte-specific functions, such as protein synthesis and cytochrome P450 (CYP450) catalytic activity. We developed a three-dimensional (3D) nanofibrous scaffold made from poly(L-lactide-co-glycolide) (PLGA) polymer using a newlyoptimizedwet electrospinning techniquethat resulted in a highly porous structure that accommodated inclusion of primary human hepatocytes. Extracellular matrix (ECM) proteins (type I collagen or fibronectin) at varying concentrations were chemically linked to electrospun PLGA using amine coupling to develop an in vitro culture system containing the minimal essential ECM components of the liver micro-environment that preserve hepatocyte function in vitro. Cell-laden nanofiber scaffolds were tested in vitro to maintain hepatocyte function over a two-week period. Incorporation of type I collagen onto PLGA scaffolds (PLGA-Chigh: 100 µg/mL) led to 10-fold greater albumin secretion, 4-fold higher urea synthesis, and elevated transcription of hepatocyte-specific CYP450 genes (CYP3A4, 3.5-fold increase and CYP2C9, 3-fold increase) in primary human hepatocytes compared to the same cells grown within unmodified PLGA scaffolds over two weeks. These indices, measured using collagen-bonded scaffolds, were also higher than scaffolds coupled to fibronectin or an ECM control sandwich culture composed of type I collagen and Matrigel. Induction of CYP2C9 activity was also higher in these same type I collagen PLGA scaffolds compared to other ECM-modified or unmodified PLGA constructs and was equivalent to the ECM control at 7 days. Together, we demonstrate a minimalist ECM-based 3D synthetic scaffold that accommodates primary human hepatocyte inclusion into the matrix, maintains long-term in vitro survival and stimulates function, which can be attributed to coupling of type I collagen.Statement of SignificanceCulturing primary hepatocytes within a three-dimensional (3D) structure that mimics the natural liver environment is a promising strategy for extending the function and viability of hepatocytes in vitro. In the present study we generate porous PLGA nanofibers, that are chemically modified with extracellular matrix proteins, to serve as 3D scaffolds for the in vitro culture of primary human hepatocytes. Our findings demonstrate that the use of ECM proteins, especially type I collagen, in a porous 3D environment helps to improve the synthetic function of primary hepatocytes over time. We believe the work presented within will provide insights to readers for drug toxicity and tissue engineering applications.

Graphical abstract

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Polyisocyanopeptide hydrogels: a novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures

Publication date: Available online 15 February 2018
Source:Acta Biomaterialia
Author(s): Jakub Zimoch, Joan Simó Padial, Agnes S. Klar, Queralt Vallmajo-Martin, Martin Meuli, Thomas Biedermann, Christopher J. Wilson, Alan Rowan, Ernst Reichmann
Molecular and mechanical interactions with the 3D extracellular matrix are essential for cell functions such as survival, proliferation, migration, and differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. This is a synthetic, thermo-responsive and stress-stiffening material synthesized via polymerization of the corresponding monomers using a nickel perchlorate as a catalyst. It can be tailored to meet various demands of cells by modulating its stiffness and through the decoration of the polymer with short GRGDS peptides using copper free click chemistry. These peptides make the hydrogels biocompatible by mimicking the binding sites of certain integrins.This study focuses on the optimization of the PIC polymer properties for efficient cell, tissue and organ development. Screening for the optimal stiffness of the hydrogel and the ideal concentration of the GRGDS ligand conjugated with the polymer, enabled cell proliferation, migration and differentiation of various primary cell types of human origin. We demonstrate that fibroblasts, endothelial cells, adipose-derived stem cells and melanoma cells, do survive, thrive and differentiate in optimized PIC hydrogels. Importantly, these hydrogels support the spontaneous formation of complex structures like blood capillaries in vitro. Additionally, we utilized the thermo-responsive properties of the hydrogels for a rapid and gentle recovery of viable cells. Finally, we show that organotypic structures of human origin grown in PIC hydrogels can be successfully transplanted subcutaneously onto immune-compromised rats, on which they survive and integrate into the surrounding tissue.Statement of SignificanceMolecular and mechanical interactions with the surrounding environment are essential for cell functions. Although 2D culture systems greatly contributed to our understanding of complex biological phenomena, they cannot substitute for crucial interaction that take place in 3D. 3D culture systems aim to overcome limitations of the 2D cultures and answer new questions about cell functions.Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. They are synthetic and can be tailor to meet certain experimental demands. Additionally, they are characterized by strain-stiffening, a feature crucial for cell behaviour, but rare in hydrogels. Their thermos-responsive properties enable quick recovery of the cells by a simple procedure of lowering the temperature.

Graphical abstract

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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans

Publication date: Available online 15 February 2018
Source:Cell Metabolism
Author(s): Adil Mardinoglu, Hao Wu, Elias Bjornson, Cheng Zhang, Antti Hakkarainen, Sari M. Räsänen, Sunjae Lee, Rosellina M. Mancina, Mattias Bergentall, Kirsi H. Pietiläinen, Sanni Söderlund, Niina Matikainen, Marcus Ståhlman, Per-Olof Bergh, Martin Adiels, Brian D. Piening, Marit Granér, Nina Lundbom, Kevin J. Williams, Stefano Romeo, Jens Nielsen, Michael Snyder, Mathias Uhlén, Göran Bergström, Rosie Perkins, Hanns-Ulrich Marschall, Fredrik Bäckhed, Marja-Riitta Taskinen, Jan Borén
A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum β-hydroxybutyrate concentrations, reflecting increased mitochondrial β-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.

Graphical abstract

Teaser

Mardinoglu et al. use multi-omics to investigate the effects of a carbohydrate-restricted diet in obese NAFLD patients. They show that the diet improves liver fat metabolism, promotes rapid shifts in the gut microbiota, increases circulating folate, and upregulates expression of genes involved in folate-dependent one-carbon metabolism in the liver.


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Insomnia and hypertension: a systematic review

Insomnia is a prevalent sleep disorder associated with a multitude of health consequences. Particularly, insomnia has been associated with cardiovascular disease and its precursors, such as hypertension and blood pressure (BP) non-dipping. The present systematic review aimed to summarize the evidence on the concurrent and prospective associations between insomnia and hypertension and/or BP. Using electronic search engines (PUBMED, SCOUPUS, PSYCHINFO), 5,618 articles published from January 1970 to December 2017 were identified, and 64 met the inclusion criteria (n=26 to 162,121; age range: 18-100; 46.4% male).

http://ift.tt/2o2Y38K

Who eats with family and how often? Household members and work styles influence frequency of family meals in urban Japan

Publication date: 1 June 2018
Source:Appetite, Volume 125
Author(s): Wakako Takeda, Melissa K. Melby, Yuta Ishikawa
Family commensality, or meals eaten together with family members, is a key practice to understand the socio-cultural organization of eating and family lives. Yet empirical evidence is limited outside of western societies, which have different household structures, work styles, and socio-cultural constructions of the practice. This study examined frequencies of family commensality based on 242 surveys of Japanese adults aged between 20 and 85 in two metropolitan areas. Results showed that family commensality is less frequent not only among those living alone, but also among those living with only non-partners including adult children, parents, and non-family members, than among those living with partners. Full-time employment was associated with late dinner times on weekdays. Later weekday dinner times were strongly associated with reduced frequency of dinners together. Late dinners have become commonplace among full-time workers in postwar Japan, and the peak dinner time in Japan occurs later than in other developed countries. Thus, work and lifestyle constraints impacting schedules appear to influence the frequency of family commensality. Our results suggest that frequencies of family commensality are influenced by co-residents and work styles of participants rather than household sizes. The idea that reduction of household size drives reduction of family commensality may be biased by previous studies conducted in western countries where most people reside in either single or nuclear households. Our study highlights complex determinants of family commensality, beyond presence of other household members, and demonstrates a need for rigorous investigation of family commensality across cultures.



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Fat-specific protein 27 is a novel target gene of liver X receptor α

Publication date: Available online 15 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Daisuke Aibara, Kimihiko Matsusue, Soichi Takiguchi, Frank J. Gonzalez, Shigeru Yamano
Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation. The nuclear hormone receptor liver X receptor α (LXRα) also plays a critical role in the control of TG levels in the liver. The present study demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRα. Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two LXR-responsive elements (LXREs) are necessary for LXRα-dependent induction of Fsp27a and Fsp27b promoter activities. Furthermore, the LXRα/retinoid X receptor α complex is capable of directly binding to the two LXREs both in vitro and in vivo. These results suggest that LXRα positively regulates Fsp27a and Fsp27b expression through two functional LXREs. Fsp27a/b are novel LXR target genes in the ob/ob fatty liver.



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Effects of growth agents and mercury on several herbs

Abstract

The paper discussed the effects of growth agents and mercury on the growth of four herb species subjected to a pot experiment: Aloe vera, Setcreasea purpurea, Chlorophytum comosum, and Oxalis corniculata. We determined the height and biomass production of selected plants treated with different growth agents and different concentrations of mercury solutions. We evaluated the relative growth rate (RGR) of the experimental plants. The aim of the study was to explore potential novel solutions to the shortcoming of the low speed of phytoremediation. The results showed that the upper parts of Aloe vera and Chlorophytum comosum had the fastest growth in the treatment with water only. In contrast, the upper parts of Setcreasea purpurea grew most intensely after the treatment with Lvyebao Fertilizer, whereas the aboveground parts of Oxalis corniculata had the fastest growth after the application of water and the occasional use of Green Cake Fertilizer. In addition, the tolerance to mercury of Oxalis corniculata was the strongest, whereas that of Chlorophytum comosum was the lowest among the species investigated.

http://ift.tt/2Etgc66

Inferential language use by school-aged boys with fragile X syndrome: Effects of a parent-implemented spoken language intervention

Publication date: Available online 15 February 2018
Source:Journal of Communication Disorders
Author(s): Sarah Nelson, Andrea McDuffie, Amy Banasik, Robyn Tempero Feigles, Angela John Thurman, Leonard Abbeduto




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Rhythmic performance in hypokinetic dysarthria: Relationship between reading, spontaneous speech and diadochokinetic tasks

Publication date: Available online 15 February 2018
Source:Journal of Communication Disorders
Author(s): Anja Lowit, Agata Marchetti, Stephen Corson, Anja Kuschmann




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Efficacy of intensive voice feminisation therapy in a transgender young offender

Publication date: March–April 2018
Source:Journal of Communication Disorders, Volume 72
Author(s): Sterling Quinn, Nathaniel Swain
Research suggests that transgender young offenders are a uniquely vulnerable caseload that may benefit from speech pathology intervention to help bring their voice into alignment with their gender identity. However, no previous studies have investigated treatment efficacy in this population. This study investigated the impact of intensive voice feminisation therapy targeting fundamental frequency and oral resonance in a 17 year old transgender individual within a youth justice institution. Acoustic analysis, listener and self-ratings of vocal femininity, self-ratings of vocal satisfaction, a post-treatment structured interview, and pre- and post- treatment completion of the Transsexual Voice Questionnaire (TVQ^MtF) were utilised to determine treatment impact. Outcome measures indicated therapy was effective at increasing the client's vocal pitch and perceptually femininity without compromising vocal quality. However, the client was still not consistently perceived as female post-intervention and had difficulty implementing feminine speech strategies in discourse. This case study provides preliminary evidence for the effectiveness of intensive voice feminisation therapy in a youth offending population. This research also highlights the potential utility of speech pathologists working in youth justice settings, even when the timeframe for intervention is limited. Furthermore, this research paper validates the use of perceptual outcome measures in transgender voice work, by replicating previous findings in which significant correlations were found between perceptual ratings of vocal gender and client satisfaction.



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From child autistic symptoms to parental affective symptoms: A family process model

Publication date: April 2018
Source:Research in Developmental Disabilities, Volume 75
Author(s): Kevin Ka Shing Chan, Chun Bun Lam, Naska Chung Wa Law, Ryan Yat Ming Cheung
BackgroundDepression and anxiety are prevalent among parents of children with autism spectrum disorder (ASD), but limited research has investigated why parenting a child with ASD is associated with elevated distress and increased risks of mental health problems. We responded to this gap in the literature by examining the associations between child autistic symptoms and parental affective symptoms, as well as the potential underlying mechanisms. Guided by a family process theory, we hypothesized that child autistic symptoms would be positively associated with parental depressive and anxiety symptoms, and that these associations would be mediated by parents' concerns about their children's characteristics (future-related worry), parental roles (parenting stress), marital relationships (marital conflicts), and family conditions (family economic pressure).MethodsCross-sectional questionnaire data were collected from 375 parents of children with ASD residing in Hong Kong, China. The hypotheses were tested using structural equation modeling.ResultsChild autistic symptoms were positively associated with parental depressive and anxiety symptoms. These associations were mediated by future-related worry, parenting stress, marital conflicts, and family economic pressure.ConclusionsOur findings revealed the potential pathways through which child autism symptomatology may adversely affect parental mental health. Our findings also highlighted the importance of designing multipronged intervention programs for families raising children with ASD in order to improve relevant family processes and reduce parental affective symptoms.



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Editorial Board

Publication date: March 2018
Source:Research in Developmental Disabilities, Volume 74





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Modulatory role of GSTT1 and GSTM1 in Punjabi agricultural workers exposed to pesticides

Abstract

Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk. A total of 513 subjects were included in this study, out of which 250 were agriculture workers and 263 were non-exposed occupationally. GSTT1 and GSTM1 null-genotype distribution was analyzed through multiplex-PCR method. Complete gene deletion in either of the genes was strongly associated with an increased risk (OR = 1.8; 95% CI = 1.3–2.6; p < 0.0008) of DNA/cytogenetic damage, cancer, infertility, and many other serious health effects. Therefore, homozygous deletion in GSTT1 or GSTM1 could play a modulatory role in health of workers with long-term exposure to pesticides.

http://ift.tt/2Gh4Nqe

Recovery and characterization of proteins from pangas ( Pangasius pangasius ) processing waste obtained through pH shift processing

Abstract

Study was conducted to recover proteins from pangas (Pangasius pangasius) processing waste (fillet frames) using pH shift method and to characterize the recovered isolates. pH 2.0 from acidic range and pH 13.0 from alkaline range were found to have maximum protein recovery (p < 0.05). During the recovery process, acidic pH (pH 2.0) was found to have minimal effect on proteins resulting in more stable isolates and strong protein gels. Alkaline pH (pH 13.0) caused protein denaturation resulting in less stable proteins and poor gel network. Both acidic and alkaline-aided processing caused significant (p < 0.05) reductions in total lipid, myoglobin, and pigment content thus by resulting in whiter protein isolates and gels. The content of total essential amino acids increased during pH shift processing, indicating the enrichment of essential amino acids. No microbial counts were detected in any of the isolates prepared using acid and alkaline extraction methods. pH shift processing was found to be promising in the utilization of fish processing waste for the recovery of functional proteins from pangas processing waste thus by reducing the supply demand gap as well pollution problems.

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Effects of vibration-induced fatigue on the H-reflex

Publication date: Available online 15 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): F. Sammali, L. Xu, C. Rabotti, M. Cardinale, Y. Xu, J.P. van Dijk, M.J. Zwarts, Z. Del Prete, M. Mischi
Vibration exercise (VE) has been suggested as an effective training for improving muscle strength and coordination. However, the underlying physiological adaptation processes are not yet fully understood, limiting the development of safe and effective exercise protocols. To better understand the neuromuscular responses elicited by VE, we aimed at investigating the acute effects of superimposed vibration on the Hoffmann reflex (H-reflex), measured after fatiguing exercise. Twenty-five volunteers performed four isometric contractions of the right Flexor Carpi Radialis (FCR) with baseline load at 80% of their maximal voluntary contraction (MVC), both with no vibration and with superimposed vibration at 15, 30, and 45 Hz. Fatigue was estimated by MVC test and estimation of electromyographic spectral compression. H-reflex suppression was estimated as the relative decrease after exercise. Our results show that fatiguing exercise determined a decrease in H-reflex amplitude compared to rest condition while vibration determined a lower H-reflex suppression as compared to no vibration. The superimposition of 30-Hz vibration determined the largest acute reduction in force generating capacity (36 N, p< 0.05) and the lowest H-reflex suppression (20%, p< 0.05). These results suggest VE to be particularly suitable in rehabilitation programs for rapid restoration of muscle form and function after immobilization periods.



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XRCC1 phosphorylation affects aprataxin recruitment and DNA deadenylation activity

Publication date: Available online 15 February 2018
Source:DNA Repair
Author(s): Julie K. Horton, Donna F. Stefanick, Melike Çağlayan, Ming-Lang Zhao, Agnes K. Janoshazi, Rajendra Prasad, Natalie R. Gassman, Samuel H. Wilson
Aprataxin (APTX) is a DNA-adenylate hydrolase that removes 5′-AMP blocking groups from abortive ligation repair intermediates. XRCC1, a multi-domain protein without catalytic activity, interacts with a number of known repair proteins including APTX, modulating and coordinating the various steps of DNA repair. CK2-phosphorylation of XRCC1 is thought to be crucial for its interaction with the FHA domain of APTX. In light of conflicting reports, the importance of XRCC1 phosphorylation and APTX function is not clear. In this study, a phosphorylation mutant of XRCC1 designed to eliminate APTX binding was stably expressed in Xrcc1^−/− cells. Analysis of APTX-GFP accumulation at micro-irradiation damage confirmed that phosphorylated XRCC1 is required for APTX recruitment. APTX-mediated DNA deadenylation activity (i.e., 5′-AMP removal) was measured in extracts of cells expressing wild-type XRCC1 or the XRCC1 phosphorylation mutant, and compared with activity in APTX-deficient and APTX-complemented human cells. APTX activity was lower in extracts from Xrcc1^−/− and XRCC1 phosphorylation mutant cells compared to the robust activity in extract from wild-type XRCC1 expressing cells. Taken together, results verify that interaction with phosphorylated XRCC1 is a requirement for significant APTX recruitment to cellular DNA damage and enzymatic activity in cell extracts.



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Effect of continuous positive airway pressure administration during lung stereotactic ablative radiotherapy: a comparative planning study

Abstract

Purpose

By increasing lung volume and decreasing respiration-induced tumour motion amplitude, administration of continuous positive airway pressure (CPAP) during stereotactic ablative radiotherapy (SABR) could allow for better sparing of the lungs and heart. In this study, we evaluated the effect of CPAP on lung volume, tumour motion amplitude and baseline shift, as well as the dosimetric impact of the strategy.

Methods

Twenty patients with lung tumours referred for SABR underwent 4D-computed tomography (CT) scans with and without CPAP (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP and noCPAP treatment plans were computed and compared for lung dose parameters (mean lung dose (MLD), lung volume receiving 20 Gy (V_20Gy), 13 Gy (V_13Gy), and 5 Gy (V_5Gy)) and mean heart dose (MHD).

Results

On average, CPAP increased lung volume by 8.0% (p < 0.001) and 6.3% (p < 0.001) at T0 and T1, respectively, but did not change tumour motion amplitude or baseline shift. As a result, CPAP administration led to an absolute decrease in MLD, lung V_20Gy, V_13Gy and V_5Gy of 0.1 Gy (p = 0.1), 0.4% (p = 0.03), 0.5% (p = 0.04) and 0.5% (p = 0.2), respectively, while having no significant influence MHD.

Conclusions

In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.

http://ift.tt/2EuDaO1

Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy

Abstract

Background and purpose

Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage.

Methods

For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery.

Results

Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement.

Conclusion

This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

http://ift.tt/2CnInBo

Nachruf für Prof. Dr. med. Dr. hc. Wilhelm Oelßner, langjähriges Ehrenmitglied der DEGRO

http://ift.tt/2ErYYd8

Occurrence of pneumonitis following radiotherapy of breast cancer – A prospective study

Abstract

Aim

of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma.

Patients and methods

A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment.

Results

A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis.

Conclusions

The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

http://ift.tt/2Cn8oku

Removal of tetracyclines, sulfonamides, and quinolones by industrial-scale composting and anaerobic digestion processes

Abstract

This study evaluated and compared the removal of antibiotics by industrial-scale composting and anaerobic digestion at different seasons. Twenty compounds belonged to three classes of widely used veterinary antibiotics (i.e., tetracyclines, sulfonamides, and quinolones) were investigated. Results show that of the three groups of antibiotics, tetracyclines were dominant in swine feces and poorly removed by anaerobic digestion with significant accumulation in biosolids, particularly in winter. Compared to that in winter, a much more effective removal (> 97%) by anaerobic digestion was observed for sulfonamides in summer. By contrast, quinolones were the least abundant antibiotics in swine feces and exhibited a higher removal by anaerobic digestion in winter than in summer. The overall removal of antibiotics by aerobic composting could be more than 90% in either winter or summer. Nevertheless, compost products from livestock farms in Beijing contained much higher antibiotics than commercial organic fertilizers. Thus, industrial composting standards should be strictly applied to livestock farms to further remove antibiotics and produce high quality organic fertilizer.

http://ift.tt/2Ggopeb

Simultaneous immobilization of cadmium and lead in contaminated soils by hybrid bio-nanocomposites of fungal hyphae and nano-hydroxyapatites

Abstract

Self-aggregation of bulk nano-hydroxyapatites (n-HAPs) undermines their immobilization efficiencies of heavy metals in the contaminated soils. Here, the low-cost, easily obtained, and environment-friendly filamentous fungi have been introduced for the bio-matrices of the hybrid bio-nanocomposites to potentially solve such problem of n-HAPs. According to SEM, TEM, XRD, and FT-IR analyses, n-HAPs were successfully coated onto the fungal hyphae and their self-aggregation was improved. The immobilization efficiencies of diethylene-triamine-pentaacetic acid (DTPA)-extractable Cd and Pb in the contaminated soils by the bio-nanocomposites were individually one to four times of that by n-HAPs or the fungal hyphae. Moreover, the Aspergillus niger-based bio-nanocomposite (ANHP) was superior to the Penicillium Chrysogenum F1-based bio-nanocomposite (PCHP) in immobilization of Cd and Pb in the contaminated soils. In addition, the results of XRD showed that one of the potential mechanisms of metal immobilization by the hybrid bio-nanocomposites was dissolution of n-HAPs followed by precipitation of new metal phosphate minerals. Our results suggest that the hybrid bio-nanocomposite (ANHP) can be recognized as a promising soil amendment candidate for effective remediation on the soils simultaneously contaminated by Cd and Pb.

http://ift.tt/2HkpWB8

Influence of Mn 2+ ions on the corrosion mechanism of lead-based anodes and the generation of heavy metal anode slime in zinc sulfate electrolyte

Abstract

The influence of Mn²⁺ ions on the generation of heavy metal anode slime during zinc electrolysis industry was extensively investigated using several electrochemical methods, electron microscope technologies, and particle size analysis. Results showed that the Mn²⁺ could obviously promote oxygen evolution reaction (OER) and thereby weaken oxidation efficiency of Mn²⁺ (η_MnO2) and dissolution of Pb²⁺. The significant improvement in kinetic parameters for OER was found in electrolytes of 1 and 3 g/L Mn²⁺, but became unstable as the Mn²⁺ concentration increased to 10 g/L. This result was correlated with much different properties of oxide layers that its changes of microstructure are involved in, since it confirmed that the positive role of compact oxide layers in contributing to high corrosion resistance and activity for OER, but excessive Mn²⁺, resulted in its micromorphology of overthickness and instability. Such differences resulted from the effect of the Mn²⁺ concentration fluctuation on kinetic rates of the nucleation growth process. The formation and adsorption of intermediate MnO₂–OH_ads identified as the controlled step for Mn²⁺ catalyzing OER was also recommended. The generation mechanism of anode slime was found to be changed in essence due to varying Mn²⁺ concentrations. In electrolyte of 1 g/L Mn²⁺, results revealed that the root cause of excessive small suspended anode slime (around 20 μm) was the change of the initial pathway of Mn²⁺ electro-oxidation, whereas, it showed great improvement in the settling performance as the Mn²⁺ concentration was increased to 10 g/L. Considering the potential of optimizing Mn²⁺ concentrations as a cleaner approach to control anode slime, deepening the understanding of the impact mechanism of Mn²⁺ can provide new insights into intervention in the generation of anode slime.

http://ift.tt/2GfCk4a

Dissolved organic matter distribution and its association with colloidal aluminum and iron in the Selenga River Basin from Ulaanbaatar to Lake Baikal

Abstract

The Selenga River Basin (Mongolia and Russia) has suffered from heavy metal contamination by placer gold mining and urban activities in recent decades. The objectives of this study were to provide the first distribution data of dissolved organic matter (DOM) and humic substances (HS) in this data-scarce region, and to investigate their association with dissolved and colloidal metals. Two sampling campaigns were conducted in August of 2013 and 2014. A constant proportion of HS (%HS; coefficient of variation of 2%) was observed from the headwater of Tuul River to the end of the delta before Lake Baikal, spanning > 1000 km in distance. The relationships were determined as [HS] = 0.643 × [DOM] (R² = 0.996, P < 0.001), and this value (%HS = 64.3) is recommended as an input parameter for metal speciation modeling based on samples collected from the rivers. The DOM and metal (Al and Fe) concentrations in samples doubled through the Zaamar Goldfield mining area, but the influence was mitigated by mixing with the larger Orkhon River, which has better water quality. Metals were mainly present as colloids and had a strong positive correlation with DOM (Al r = 0.81, P < 0.01; Fe r = 0.61, P < 0.01), suggesting that DOM sustains colloidal Al and Fe in solution and they are co-transported in the Selenga River Basin. Land use changes affect water quality and metal speciation and therefore have major implications for the fate of metals.

http://ift.tt/2F7dgx8

Effects of 915 nm laser irradiation on human osteoblasts: a preliminary in vitro study

Abstract

Photobiomodulation (PBM) is a non-invasive treatment that uses laser or led devices making its effects a response to light and not to heat. The possibility of accelerating dental implant osteointegration and orthodontic movements and the need to treat refractory bone lesions, such as bisphosphonate related osteonecrosis of the jaws, has led researchers to consider the effects of PBM on bone for dentistry purposes. The aim of our study was to investigate the effects of 915 nm light supplied with a GaAs diode laser on human osteoblasts in vitro. Osteoblasts were isolated from mandibular cortical bone of a young healthy donor. The irradiation parameters were as follows: doses = 5, 15 and 45 J/cm²; power densities = 0.12 and 1.25 W/cm²; and irradiation times = 41.7, 125 and 375 s. We performed one irradiation per day for 3 and 6 days to study proliferation and differentiation, respectively. Microscopic analysis showed a greater amount of bone nodules in samples treated with 5 J/cm² and 0.12 W/cm² compared to controls (56.00 ± 10.44 vs 19.67 ± 7.64, P = 0.0075). Cell growth and quantification of calcium deposition did not show any differences when comparing irradiated and non-irradiated samples. Photobiomodulation, with the parameters investigated in the present study, positively modulated the mineralization process in human osteoblasts, inducing the formation of a greater amount of bone nodules, but did not increase cell proliferation.

http://ift.tt/2F67P1d

Effect of prior application with and without post-injury treatment with low-level laser on the modulation of key proteins in the muscle repair process

Abstract

The aim of the present study was to evaluate the effects of LLLT prior to muscle injury with and without post-injury irradiation on the expression of isoforms of myosin heavy chain (MyHC), calcineurin (CaN), and myostatin during the repair process. Wistar rats were divided into five groups: control (n = 7); injury (n = 21); LLLT + injury (n = 21); injury + LLLT (n = 21), and LLLT + injury + LLLT (n = 21). Cryoinjury was performed on the tibialis anterior (TA) muscle. The injured groups were euthanized at 3, 7, and 14 days after injury. LLLT was performed using an infrared laser (780 nm) with the following parameters: 10 J/cm², 40 mW, 10 s per point, 8 points, and 3.2 J of total energy. At the end of each period, the TA muscle was removed for the analysis of MyHC, CaN, and myostatin gene expression using real-time PCR. The data were tested statistically by Kruskal-Wallis with Dunn's post hoc test (p < 0.05). The results demonstrated that prior irradiation reduced the mRNA expression of all proteins at 3 days. Post irradiation reduced the mRNA expression of MyHC-1, MyHC-2a, MyHC-2b, and CaN at 7 days. Prior irradiation combined with post-injury irradiation reduced the mRNA expression of MyHC-2x and CaN at 14 days and increased the mRNA expression of myostatin in the same period. In conclusion, different protocols of photobiomodulation can modulate the expression of the different isoforms of MyHC, CaN, and myostatin during the repair process. It is noteworthy that the combination of the prior and post-injury irradiation was the protocol that most promoted changes in the final phase of the repair process.

http://ift.tt/2Epk3kn

Rehabilitative orbital decompression for Graves’ orbitopathy: results of a randomized clinical trial

Abstract

Purpose

Orbital decompression (OD) is a consolidated procedure for the treatment of exophthalmos in Graves' orbitopathy (GO). The efficacy of the various procedures remains unclear due to the variability of the techniques used. To address this issue, we performed a randomized clinical trial to compare the efficacy of two surgical techniques. The primary endpoint was the reduction in proptosis. Secondary aims were the risk of post-operative diplopia (POD) in primary gaze and other surgical complications.

Patients

38 patients (76 orbits) affected with GO were enrolled and randomized into single lateral decompression (LD) (n = 19) or balanced medial plus lateral wall decompression (MLD) (n = 19). Following surgery, patients were seen for a follow-up ophthalmological evaluation at 6 months. Pre-operative diplopia in secondary gaze was present in 13/38 patients (34.2%, 8/19 treated with LD and 5/19 treated with MLD).

Results

The reduction of exophthalmos was greater in patients treated with MLD (5.1 ± 1.5 mm, range 2–8 mm) than in those treated with LD (3.5 ± 1.3 mm, range 1–6.5 mm) (p = 0.01). The overall incidence of POD in primary gaze was 5/38 (13.2%) and all of these patients had pre-operative diplopia in secondary gaze (5/13, 38.5%, vs patients with no pre-operative diplopia p = 0.005). Two of 19 patients (10.5%) treated with LD and 3/19 (15.8%) treated with MLD, developed POD in primary gaze, with no statistical difference between the two techniques.

Conclusion

MLD provides a better result in terms of proptosis reduction compared to LD. The two techniques used here appear to have a similar safety profile in terms of POD. Pre-operative diplopia in the secondary gaze remains a major risk factor for development of POD.

http://ift.tt/2syLBSP

20S proteasome in the blood plasma of boys with cryptorchidism

Abstract

Purpose

To evaluate the concentration of 20S proteasome in the blood plasma of boys with cryptorchidism.

Methods

Patients—50 boys aged 1–4 years (median = 2.4 years) with unilateral cryptorchidism. The control group—50 healthy, age-matched boys (aged 1–4 years, median = 2.1 years), admitted for planned herniotomy. In our study, we used a novel technique Surface PLASMON RESONANCE Imaging.

Results

The median concentration of 20S proteasome in the blood plasma of boys with cryptorchidism was 2.5-fold higher than in boys with inguinal hernia. We noticed statistically significant difference between 20S proteasome levels in boys with cryptorchidism up to 2 years old and above 2 years old.

Conclusions

We believe that the 20S proteasome concentrations in the blood plasma of boys with cryptorchidism reflect the heat-induced apoptosis of germ cells.

http://ift.tt/2EGkudI

Functional implications of inhibitory synapse placement on signal processing in pyramidal neuron dendrites

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Josiah R Boivin, Elly Nedivi
A rich literature describes inhibitory innervation of pyramidal neurons in terms of the distinct inhibitory cell types that target the soma, axon initial segment, or dendritic arbor. Less attention has been devoted to how localization of inhibition to specific parts of the pyramidal dendritic arbor influences dendritic signal detection and integration. The effect of inhibitory inputs can vary based on their placement on dendritic spines versus shaft, their distance from the soma, and the branch order of the dendrite they inhabit. Inhibitory synapses are also structurally dynamic, and the implications of these dynamics depend on their dendritic location. Here we consider the heterogeneous roles of inhibitory synapses as defined by their strategic placement on the pyramidal cell dendritic arbor.



http://ift.tt/2o2jMh4

Application of graphene-based flexible antennas in consumer electronic devices

Publication date: Available online 15 February 2018
Source:Materials Today
Author(s): A. Scidà, S. Haque, E. Treossi, A. Robinson, S. Smerzi, S. Ravesi, S. Borini, V. Palermo
We describe the fabrication and characterization of Near-Field Communication (NFC) devices based on highly flexible, carbon-based antennas composed of stacked graphene multilayers. This material features a high value of conductivity (4.20 * 10⁵ S/m) comparable to monocrystalline graphite, but is much more flexible and processable. We first studied the replacement of metal with carbon antennas using computer modeling, to select the best design. Then we manufactured several devices to be used according to the communication protocol ISO/IEC 15693. The inductance of the G-paper antennas was tested before and after hundreds of thousands of bending cycles at bending radii of 45 and 90 mm. During bending the self-resonance frequency and inductance peak showed minimal variation and the resistance at 1 MHz changed from 33.09 Ω to 34.18 Ω, outperforming standard, commercial metallic antennas. The devices were successfully tested by exchanging data with a smartphone and other commercial NFC readers, matching the performance of standard, commercial metallic antennas. The graphene antennas could be deposited on different standard polymeric substrates or on textiles. Smart cards, flexible NFC tags and wearable NFC bracelets were prepared in this way to be used in electronic keys, business cards and other typical NFC applications.

Graphical abstract

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Response rates and recurrence patterns after low-dose radiotherapy with 4 Gy in patients with low-grade lymphomas

Abstract

Purpose

Retrospective study of effectiveness, toxicity, and relapse patterns after low-dose radiotherapy (LDRT) in patients with low-grade lymphomas.

Methods

47 patients (median age 64 years) with 50 lesions were treated with LDRT (2 × 2 Gy). In 60%, LDRT was the primary and curative treatment, in 40% offered as second-line therapy in recurrent disease. Histology included follicular (57%) and marginal zone lymphomas (43%). Patients were followed-up regularly clinically (skin) and with CT or MRI scans.

Results

Median follow-up was 21 months. 84% of the lesions were extranodal disease (32% orbit, 14% salivary glands, 30% skin, and 8% others). Most lesions were ≤5 cm (90%) with a singular affection (74%). 26% of the patients received rituximab simultaneously. Overall response rate (ORR) was 90% (all lesions), 93.3% (primary treatment), and 85% (recurrence treatment); p = 0.341. 2‑year Local progression-free survival (LPFS) for all, curative, and palliative patients was 91.1%, 96.7%, and 83.8%, respectively; p = 0.522. Five relapses were detected: three infield only, and were therefore treated with LDRT or subsequent local RT of 30 Gy. Two patients showed an in- and outfield progression and were consequently treated with chemotherapy. Predictive factors for higher LPFS were tumor size ≤5 cm (p = 0.003), ≤2 previous treatments (p = 0.027), no skin involvement (p = 0.05), singular affection (p = 0.075), and simultaneous rituximab application (p = 0.148). LDRT was tolerated well, without detectable acute or long-term side effects.

Conclusion

Primary LDRT is an effective treatment with high ORR and long-lasting remissions in a subset of patients with low-grade lymphoma, and may therefore be a curative treatment option for patients with low tumor burden. LDRT with the CD20 antibody obinutuzumab will soon be tested in a prospective multicenter trial.

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Fetal exposure markers of dioxins and dioxin-like PCBs

Abstract

Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p-dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been associated with a number of adverse health outcomes. Although the placenta acts as a barrier between the mother and the fetus, these contaminants transfer through the placenta exposing the fetus. Several studies have investigated placental transfer, but few have assessed the co-variation among these contaminants. Maternal blood, cord blood, and cord tissue were collected from 41 Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs. Hierarchical cluster analysis followed by principal component analysis were used to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs was present in all three matrices with 2,3',4,4',5-PeCB(#118) and 3,3',4,4',5-PeCB(#126) explaining the majority of the clusters' variances. Medium/high chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not in cord tissue. 2,3,4,4',5-PeCB(#114) and 2,3,3',4,4',5,5'-HpCB(#189) explained the majority of the clusters' variances. There was a substantial correlation between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The sum of the four suggested PCBs plus 3,3',4,4'-TeCB(#77) correlated well with total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co-variation existed among the studied contaminants. The five PCBs can be used as fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be measured as well.

http://ift.tt/2EIUJJr

How can water quality be improved when the urban waste water directive has been fulfilled? A case study of the Lot river (France)

Abstract

The Lot river, a major tributary of the downstream Garonne river, the largest river on the Northern side of the Pyrenees Mountains, was intensively studied in the 1970s. A pioneering program called "Lot Rivière Claire" provided a diagnosis of water quality at the scale of the whole watershed and proposed an ambitious program to manage nutrient pollution and eutrophication largely caused by urban wastewater releases. Later on, the implementation of European directives from 1991 to 2000 resulted in the nearly complete treatment of point sources of pollution in spite of a doubling of the basin's population. At the outlet of the Lot river, ammonium and phosphate contamination which respectively peaked to 1 mg N-NH₄ L⁻¹ and 0.3 mg P-PO₄ L⁻¹ in the 1980s returned to much lower levels in recent years (0.06 mg N-NH₄ L⁻¹ and 0.02 mg P-PO₄ L⁻¹), a reduction by a factor 15. However, during this time, nitrate contamination has regularly increased since the 1980s, from 0.5 to 1.2 mg N-NO₃ L⁻¹ in average, owing to the intensification of agriculture and livestock farming. Application of the Riverstrahler model allowed us to simulate the water quality of the Lot drainage network for the 2002–2014 period. We showed that, with respect to algal requirements, phosphorus and silica are well balanced, but nitrogen remains largely in excess over phosphorus and silica. This imbalance can be problematic for the ecological status of the water bodies. Using the model, for simulating various scenarios of watershed management, we showed that improvement of urban wastewater treatment would not result in any significant change in the river's water quality. Even though arable land occupies a rather limited fraction of the watershed area, only the adoption of better farming practices or more radical changes in the agro-food system could reverse the trend of increasing nitrate contamination.

http://ift.tt/2o6uJxo

Virtual reality for upper limb rehabilitation in sub-acute and chronic stroke: a randomized controlled trial

Publication date: Available online 14 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Pawel Kiper, Andrzej Szczudlik, Michela Agostini, Jozef Opara, Roman Nowobilski, Laura Ventura, Paolo Tonin, Andrea Turolla
ObjectiveTo evaluate the effectiveness of reinforced feedback in virtual environment (RFVE) treatment combined with conventional rehabilitation (CR) in comparison with CR alone, and to study whether changes are related to stroke aetiology (i.e. ischemic or hemorrhagic).DesignRandomized controlled trial.SettingInpatients in a hospital facility for intensive rehabilitation.Participants136 patients within one year from onset of a single stroke.InterventionsThe experimental treatment was based on the combination of RFVE with CR, while control treatment was based on the same amount of CR. Both treatments lasted 2 hours daily, 5 days a week, for 4 weeks.Main Outcome MeasuresFugl-Meyer upper extremity (F-M UE) scale (primary outcome), Functional Independence Measure (FIM), National Institutes of Health Stroke Scale (NIHSS), and Edmonton Symptom Assessment Scale (ESAS) (secondary outcomes). Kinematic parameters of requested movements: duration (Time), mean linear velocity (Speed), number of submovements (Peak) (secondary outcomes).Results136 patients (ischemic=78, hemorrhagic=58) were randomized in two groups (RFVE=68, CR=68) and stratified by stroke aetiology (ischemic, hemorrhagic). Both groups improved after treatment, but the experimental group had better results than the control group (Mann-Whitney U test) at: F-M UE (p<0.001), FIM (p<0.001), NIHSS (p≤0.014), ESAS (p≤0.022), Time (p<0.001), Speed (p<0.001), Peak (p<0.001). Stroke aetiology did not have significant effects on patient outcomes.ConclusionThe RFVE therapy combined with CR treatment promotes better outcomes for upper limb than the same amount of CR, regardless of stroke aetiology (Clinical Trial Registration – NCT01955291).



http://ift.tt/2ELV3aJ

Toward a meaningful definition of recovery after hip fracture: Comparing two definitions for community-dwelling older adults

Publication date: Available online 14 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mohammad Auais, Suzanne N. Morin, Lois Finch, Sara Ahmed, Nancy Mayo
ObjectivesTo examine the course of recovery and resulting health-related quality of life (HRQL) after low-trauma hip fracture using two different definitions of recovery.DesignInception cohort with eight assessments over one year.SettingParticipants were recruited from a tertiary-care hospital and followed in the community.InterventionNot applicableParticipants47 (75% of all eligible) community-dwelling hip fracture patients (≥65 years).Main Outcome MeasuresPre-fracture functional level was used to identify subgroups of participants with similar trajectories of mobility over time. Recovery in functional mobility was defined in two ways: the "traditional" definition (return to pre-fracture level of functional mobility) and a "targeted recovery" definition (ability to climb 10 steps); both were measured using the Lower Extremity Functional Scale. HRQL was measured using the RAND-36.ResultsParticipants were categorized into three subgroups: low, medium, and high pre-fracture functional abilities. Agreement between the two definitions of recovery (quantified using Kappa coefficient) was strong for the medium group (0.81; 95% CI: 0.56-1.00), weak for the high group (0.46; 95% CI: 0.0-0.99), and minimal for the low group (0.12; 95% CI: 0.0-0.328).Contrary to the traditional definition, patients who achieved targeted recovery had statistically and clinically better HRQL than the rest of the cohort throughout the study (estimated average difference =10.8 points on RAND-36; 95% CI: 6.67-15.07).ConclusionThe agreement between the two definitions of recovery ranged from minimal to strong according to patient group. Using a functional target to define recovery predicted HRQL better. It is vital to consider the definition of recovery carefully for research or clinical practice because it can influence subsequent decisions (e.g. endorsing a specific intervention or discharging patients).



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The Danger of Applying the ProtecT Trial to Minority Populations

This Viewpoint examines the generalizability of the results of ProtecT Trial to minority populations.

http://ift.tt/2Co79kO

Oregon’s Death With Dignity Act

To the Editor The article by Blanke et al provides an optimistic examination of physician-assisted suicide, especially in relation to cancer research. However, this seems to be a slippery slope to tread. By the authors' own admission, there are only a small number of cases in which physician-assisted suicide was used as a means of pain relief, with the others citing reasons of autonomy, lack of enjoyment in life, and a lessening of their dignity. If society already approves of the use of physician-assisted suicide in cases not based on physical pain, it logically follows that more and more controversial reasons for physician-assisted suicide become acceptable. There is no clear place to draw the line.

http://ift.tt/2EuN1Uj

Prognostic Signatures for Estrogen Receptor–Positive Breast Cancer

This secondary analysis of a randomized clinical trial evaluates the prognostic value of 6 multigene signatures in women with early estrogen receptor–positive breast cancer who have received 5 years of endocrine therapy.

http://ift.tt/2Cnf9me

Oregon’s Death With Dignity Act—Reply

In Reply We read with interest Sperling's letter, which raised 3 concerns regarding our article on Oregon's Death With Dignity Act. First, the letter noted that only a small fraction of the patients discussed in our article used medical aid in dying (MAID) (note that our article and the letter both used older terms for this therapeutic option) because of uncontrolled pain. Our point was that unrelieved pain is a truly unfortunate reason underlying MAID use, in that dedicated palliative care should be able to relieve physical discomfort in nearly all cases. Sperling suggests that it would be better to draw the line between pain relief and other "approved" but controversial reasons (eg, loss of dignity), and that society will continue to accept even more provocative motives underlying the patient's decision for MAID. While we are interested in whether we can better palliate patient concerns and alleviate the need for MAID, we do point out that there is no requirement for society, the attending physician, family, or anyone else to legally approve the patient's reason for seeking MAID. Oregon tracks that information, but the option of using MAID is not subject to disapproval, regardless of why the patient desires it.

http://ift.tt/2EtLYE6