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.
http://ift.tt/2EGC41d
Πέμπτη 15 Φεβρουαρίου 2018
Brain activations supporting linking of action phases in a sequential manual task
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.
http://ift.tt/2oa5x9c
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.
http://ift.tt/2o2RvHq
Social Factors in the Development of Chronic Rhinosinusitis: a Systematic Review
Abstract
Purpose of Review
In an era where prevention is paramount, understanding social factors for chronic rhinosinusitis (CRS) may facilitate preventive interventions that mitigate risk factors associated with the initiation or progression of the disease.
Recent Findings
Both passive and active smoking are clearly and unequivocally associated with both the incidence and the severity of rhinosinusitis, while there an increasing body of evidence linking social deprivation and low socioeconomic status with rhinosinusitis and its complications. However, overall, only a handful of studies were longitudinal, while the available studies suffer from lack of standardized definitions of rhinosinusitis.
Summary
In this systematic review, we assessed the available evidence linking CRS with social factors, such as socioeconomic status and class, educational status, family status, living and working location and conditions, and use of toxins or recreational drugs as well as exercise and diet. Thirty studies from 1995 onwards fulfilled our inclusion criteria and were used for this review. Social deprivation and low socioeconomic level seem to be directly associated with rhinosinusitis, as there are pollutants in living or working environment. A clear and direct association between smoking (both active and passive) and rhinosinusitis was also shown. However, the link between rhinosinusitis and education level, and exercise and diet, if any, seems to be more complex.
http://ift.tt/2C31LYX
Systematic Reviews and Meta-analysis in Rhinosinusitis: a Critical Review of the Reviews
Abstract
Purpose of Review
There has been an explosion in the number of published systematic reviews on chronic rhinosinusitis in the last decade.
Recent Findings
While the aim of these reviews in facilitating evidence-based practice is laudable, poor quality reviews may contain significant bias that can mislead a non-discerning reader.
Summary
Attention therefore must be given to review methodology before implanting findings. Organisations such as the Cochrane Collaboration promote high-quality reviews, but are limited in chronic sinus disease by heterogeneous outcomes and a paucity of randomised trials.
http://ift.tt/2sxmiAV
Neurotrophins in Asthma
Abstract
Purpose of Review
Asthma is a chronic airway disease that affects more than 300 million people worldwide. Current treatment focuses on symptomatic relief by temporally dampening inflammation and relaxing the airway. Novel combative strategies against asthma and hopefully a cure are yet to be developed. The goal of this review is to summarize recent literature on neurotrophins (NTs) in experimental models and clinical settings of asthma research.
Recent Findings
We highlight studies of early phases of asthma that collectively reveal a profound impact of elevated NT levels following initial detrimental insults on long-term airway dysfunction.
Summary
We hope this review will foster insights into the complex interaction between NTs, nerves, immune cells, and airway structural cells during a critical time window of development and disease susceptibility. Future studies are required to better understand the role of NTs in asthma pathophysiology and to evaluate whether NTs and their receptors may serve as new drug targets.
http://ift.tt/2EMs0Um
Modified Allergens for Immunotherapy
Abstract
Purpose of Review
During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT.
Recent Findings
In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens.
Summary
The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.
http://ift.tt/2sAN1wc
Occupational Animal Allergy
Abstract
Purpose of Review
This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention.
Recent Findings
(1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace.
Summary
Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.
http://ift.tt/2Hi4xbU
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.
http://ift.tt/2o3go5R
Optimizing the induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based analysis
Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Hao Peng, Ling-Long Tang, Bin-Bin Chen, Lei Chen, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Yuan Zhang, Li-Zhi Liu, Li Tian, Ying Guo, Ying Sun, Jun Ma
ObjectivesThis study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.Materials and methodsWe identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3–4 toxicities were compared between different IC regimen groups.ResultsIn total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m2 in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m2. Grade 3–4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group.ConclusionsOur study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m2, while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m2, although grade 3–4 toxic events were more common but tolerable. Further studies are needed to validate our findings.
http://ift.tt/2HkYJhJ
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.
http://ift.tt/2GhypUs
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.
http://ift.tt/2GhypUs
Editorial Board
Publication date: March 2018
Source:Dental Materials, Volume 34, Issue 3
http://ift.tt/2C3245W
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.
http://ift.tt/2BtTRql
Editorial Board
Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5
http://ift.tt/2BZMRlW
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.
Graphical abstract
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Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5
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Graphical abstract TOC
Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5
http://ift.tt/2C1nfVM
Graphical abstract TOC
Publication date: 1 March 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 5
http://ift.tt/2sCJ6iE
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
http://ift.tt/2EMW0zy
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.http://ift.tt/2o3mrXQ
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+GR1hi 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.http://ift.tt/2szzy7W
Preoperative Clinical and Sonographic Predictors for Lateral Cervical Lymph Node Metastases in Sporadic Medullary Thyroid Carcinoma
Thyroid , Vol. 0, No. 0.
http://ift.tt/2F5qrOY
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.http://ift.tt/2GhvriU
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 CD25HighFOXP3High, 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.
Graphical abstract
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.http://ift.tt/2HiLXR1
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.
http://ift.tt/2ENglVr
Diagnostik von AVWS bei Erstklässlern: Welche Tests trennen auffällige von unauffälligen Kindern?
Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-101836
Hintergrund Im kontrollierten Gruppenvergleich wurde für 2., 3. und 4.-Klässler gezeigt, dass eine Trennung von Kindern mit auditiven Verarbeitungs- und Wahrnehmungsstörungen (AVWS) von solchen ohne (Non-AVWS) durch 3 bzw. 4 Untersuchungsinstrumente möglich ist mit einer Zuordnungsrichtigkeit von 93,6 % bzw. 97,5 % 1, 2. Die vorliegende Studie erfolgte mit der Fragestellung, ob auch für Erstklässler eine Trennung der Gruppen gelingt. Material und Methoden Leistungen von 77 Kindern (n = 40 mit AVWS, mittl. Alter: 6,93, SD 0,53 Jahre; n = 37 Non-AVWS, mittl. Alter: 6,90, SD 0,52 Jahre) im 1. Regelgrundschuljahr wurden in 8 spezifisch auditiven Tests einer eklektischen AVWS-Testbatterie miteinander verglichen: Uttenweiler-Test zum Dichotischen Wortverstehen; Subtests Lautdifferenzierung u. Kinästhetik (Heidelberger Lautdifferenzierungstest- HLAD); Göttinger Sprachaudiometrie II im Störgeräusch; Hannoverscher Binauraler Summationstest; Zahlenfolgen-Gedächtnis u. Laute Verbinden (Psycholinguistischer Entwicklungstest); Mottier-Test. Ergebnisse Kinder mit AVWS wurden von unauffälligen Kindern (Non-AVWS) der gleichen Schuljahrgangsstufe in 94,8 % aller Fälle (kreuzvalidiert: in 92,2 %) statistisch signifikant durch vier Testvariablen getrennt: (1) PET-Zahlenfolgen-Gedächtnis; (2) HLAD-Lautdifferenzierung; (3) Mottier-Test; (4) Sprachaudiometrie im Störgeräusch. Schlussfolgerungen Die Qualität der diagnostischen A-Priori-Gruppierung mittels einer multivariaten Statistik konnte für das 1. Regelgrundschuljahr bestätigt werden.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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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.
http://ift.tt/2EM56wf
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.
http://ift.tt/2Cpogml
[28° CONGRESSO CHIRURGIA DELL'APPARATO DIGERENTE 14° CORSO PER INFERMIERI DI SALA OPERATORIA Presidente: Prof. Giorgio Palazzini Roma, 23-24 novembre 2017].
| Related Articles |
[28° CONGRESSO CHIRURGIA DELL'APPARATO DIGERENTE 14° CORSO PER INFERMIERI DI SALA OPERATORIA Presidente: Prof. Giorgio Palazzini Roma, 23-24 novembre 2017].
G Chir. 2017 Nov-Dec;38(6):319
Authors: Di Matteo G
PMID: 29442066 [PubMed - in process]
http://ift.tt/2CngSrK
[Steven D. WEXNER, James W. FLESHMAN CHIRURGIA DEL COLON E DEL RETTO: OPERAZIONI ADDOMINALI Piccin, Padova, 2015 Steven D. WEXNER, James W. FLESHMAN CHIRURGIA DEL COLON E DEL RETTO: OPERAZIONI ANORETTALI Piccin, Padova, 2015].
| Related Articles |
[Steven D. WEXNER, James W. FLESHMAN CHIRURGIA DEL COLON E DEL RETTO: OPERAZIONI ADDOMINALI Piccin, Padova, 2015 Steven D. WEXNER, James W. FLESHMAN CHIRURGIA DEL COLON E DEL RETTO: OPERAZIONI ANORETTALI Piccin, Padova, 2015].
G Chir. 2017 Nov-Dec;38(6):318
Authors: Di Matteo G
PMID: 29442065 [PubMed - in process]
http://ift.tt/2EuEkJr
Pilonidal disease mimicking anterior anal fistula and associated with posterior anal fistula: a two-step surgery. Case report.
| Related Articles |
Pilonidal disease mimicking anterior anal fistula and associated with posterior anal fistula: a two-step surgery. Case report.
G Chir. 2017 Nov-Dec;38(6):313-317
Authors: Eberspacher C, Mascagni D, Fralleone L, Grimaldi G, Antypas P, Mascagni P, Maturo A, Di Matteo FM, Pontone S, Pironi D
Abstract
AIM: Anal fistula is a common disease originated from abscess according the cryptoglandular theory. A rare etiology is the pilonidal disease. In our case we observed a pilonidal disease mimicking an anterior perianal fistula, associated with another posterior anal fistula.
CASE PRESENTATION: A 36-year old man was referred to our department with an anal fistula with an anterior opening. Despite the clinical examination and the endoanal ultrasound, only during the surgery we discovered the origin of the anterior fistula from a misdiagnosed pilonidal sinus. There was also a posterior anal fistula in communication with the same abscess of the anterior one. We performed a two-step surgery with a first fistulectomy of the anterior tract, a drainage of abscess and the positioning of a seton for the posterior fistula. After about one month and the fall of the seton we evaluate the good healing of posterior anal fistula and excised the residual pilonidal sinus.
CONCLUSION: This misdiagnosed pilonidal disease created in our clinical report a true challenge. Our goal was to eliminate as much disease as possible, but also to avoid major complications or recurrences. We refused an aggressive approach and chose a two-step surgery, with in the first approach not only a demolitive time but also a reconstruction to facilitate healing, and in the second time the complete eradication of the pathology.
PMID: 29442064 [PubMed - in process]
http://ift.tt/2CnUJtd
Gallstone ileus in a ninety-two years old colecistectomized patient after endoscopic biliary sphincterotomy: a case report.
| Related Articles |
Gallstone ileus in a ninety-two years old colecistectomized patient after endoscopic biliary sphincterotomy: a case report.
G Chir. 2017 Nov-Dec;38(6):299-302
Authors: Fedele S, Lobascio P, Carbotta G, Balducci G, Laforgia R, Sederino MG, Minafra M, Delvecchio A, Palasciano N
Abstract
INTRODUCTION: Gallstone ileus is an uncommon condition of mechanical bowel obstruction caused by the passage of a gallstone into the bowel. It occurs more frequently in female patients older than 65 years and often for a biliary-enteric fistula. The pathognomonic features of gallstone ileus - the Rigler's triad - are pneumobilia, ectopic gallstone and bowel obstruction. Less commonly, a gallstone may enter the intestinal lumen through the common bile duct, after endoscopic retrograde cholangiopancreatography, and very rarely in colecistectomized patient.
CASE REPORT: A 92-year old colecistectomized male patient was admitted to our unit for the clinical suspicion of bowel obstruction. He was also submitted to ERCP seven months before. Physical examination revealed tenderness in the lower abdomen and CT showed intrahepatic and extrahepatic biliary dilatation and small bowel obstruction with a hyperdense formation in right iliac fossa as gallstone ileus. It was performed an emergency laparotomy with enterotomy and a 5x3 cm gallstone removal. There were no post-operative complications and the patient was discharged 8 days after surgery.
DISCUSSION: Cholecysto-duodenal fistulas are most frequently described in worldwide-reports. There are only few cases in literature of gallstone which enter the gastrointestinal tract following endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy through papilla of Vater, without a biliary-enteric fistula, causing gallstone ileus. If the patient is cholecistectomized, gallstone removal alone is required.
CONCLUSION: The differential diagnosis in case of small bowel obstruction should always include gallstone ileus, even if the patient previously underwent a cholecystectomy.
PMID: 29442062 [PubMed - in process]
http://ift.tt/2CoeMYD
Unusual presentation of retroperitoneal Schwannoma: case report.
| Related Articles |
Unusual presentation of retroperitoneal Schwannoma: case report.
G Chir. 2017 Nov-Dec;38(6):295-298
Authors: Latino R, Bosco D, Frattallone ME, Amico A, Lanteri R, Di Cataldo A
Abstract
Schwannoma is a rare tumor that develops from the Schwann cells in the nerve sheath. A 42 years old woman was found incidentally to have a bulky mass in epigastric region. Abdominal ultrasonography CT and MRI have been of aid to know the position and size of the tumor. A massive capsulated retroperitoneal lesion was identified. It moved forward the hepatoduodenal ligament, inferior vena cava laterally and aorta medially. The mass is exte-riorized and detached from adhesions. There were no complications after the operation and the patient was discharged on the fourth post-operative day. The microscopically examina-tion showed features suggestive of Cellular Schwannoma. After 8 months during follow-up, the patient did not report any neurological deficit and control CT did not suggest the presence of recurrent disease.
PMID: 29442061 [PubMed - in process]
http://ift.tt/2Esv4FE
Modified transverse coloplasty pouch: new reconstruction techniques after total mesorectal excision. Our experience.
| Related Articles |
Modified transverse coloplasty pouch: new reconstruction techniques after total mesorectal excision. Our experience.
G Chir. 2017 Nov-Dec;38(6):285-290
Authors: Grimaldi G, Eberspacher C, Romani AM, Merletti D, Maturo A, Pontone S, Pironi D
Abstract
AIM: The incidence of rectal cancer continues to rise. The functional results after complete Total Mesorectal Excision (TME) depend on the segment of colon used for reconstruction of colonic continuity and the form, the volume and the functional proprieties of the "neorectum". The aim of our study is evaluate the efficacy of our Modified Transverse Coloplasty Pouch (MTCP) after the treatment of low rectal cancer in terms of functional outcomes and quality of life.
PATIENTS AND METHODS: The study included 136 patients, underwent TME from January 2007 to December 2016 with diagnosis of extraperitoneal carcinoma of the rectum. The average distance of the tumor from the dentate line was 5.6 cm. Our follow-up protocol included functional outcome evaluation at 7th post-operative day (POD), 2nd month, and 6th month after the surgery.
RESULTS: All patients (M/F 84/52) underwent anterior rectal resection (TME) with MTCP. Frequency of bowel movements per 24 hours in the studied patients compared at 7th POD, 2 months, and 6 months. Since the first post-operative weeks there is an encouraging reduction of the frequency of bowel movements.
CONCLUSION: Modified Transverse Coloplasty Pouch (MTCP) had better functional results and quality of life compared to patients with a Colonic J Pouch (CJP) and traditional Transverse Coloplasty Pouch (TCP).
PMID: 29442059 [PubMed - in process]
http://ift.tt/2Ev75pj
Multiparametric evaluation of risk factors associated to seroma formation in abdominal wall surgery.
| Related Articles |
Multiparametric evaluation of risk factors associated to seroma formation in abdominal wall surgery.
G Chir. 2017 Nov-Dec;38(6):280-284
Authors: Licari L, Salamone G, Parinisi Z, Campanella S, Sabatino C, Ciolino G, De Marco P, Falco N, Boventre S, Gulotta G
Abstract
INTRODUCTION: Incisional hernia is one of the main topics in the general surgery since there is not a unanimous consensus concerning to the best surgical methodology to adopt. It seems that prosthetic surgery is the best technique, even if responsible for the development of periprosthetic seroma. The aim of this study is to assess whether the preoperative abnormalities of the bio-humoral parameters may be considered as risk factors for seroma.
PATIENTS AND METHODS: From July 2016 to July 2017 at the "Policlinico Paolo Giaccone", Palermo, Department of Emergency Surgery, 56 patients included in this study, underwent laparotomic mesh repair. The inclusion criteria were: age > 18 years, incisional hernia W2R0 according to the Chevrel classification and a monoperator technique. The main variables were: sex, age, BMI, smoke, ASA score, and co-morbidities. Among the main serum-blood variables: natraemia, kalaemia, chloraemia, calcaemia, PCR, level of glucose, creatinine, albumin and proteins in the blood. The data were analyzed using SPSS software.
RESULTS: Univariate analysis highlighted hypo- and hyper-natraemia, hyper-kalaemia, hypo-chloraemia, high levels of PCR, hyper-glycemia, low level of serum-blood albumin and proteins, as statistically significant variables. Multivariate analysis revealed a p<0.05 for PCR, hypo-albuminemia and total serum-blood-protein level.
CONCLUSIONS: Alterations of pre-operative bio-humoral parameters could be associated to a greater risk of seroma development. A better understanding of such alterations may lead to more efficient risk stratification methods. This could be essential to better address the medical resources, reducing the post-operative complications and the outpatient controls as well as the risk associated to seroma.
PMID: 29442058 [PubMed - in process]
http://ift.tt/2Co2Fe6
Inguinal hernia repair in day surgery: the role of MAC (Monitored Anesthesia Care) with remifentanil.
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Inguinal hernia repair in day surgery: the role of MAC (Monitored Anesthesia Care) with remifentanil.
G Chir. 2017 Nov-Dec;38(6):273-279
Authors: Palumbo P, Usai S, Amatucci C, Perotti B, Ruggeri L, Illuminati G, Tellan G
Abstract
BACKGROUND: The extension of indications for procedures in a Day Surgery (DS) setting has led to changes in the anesthetic and surgical treatment of Inguinal Hernias (IH). According to the recommendations of the European Hernia Society, the treatment of IH in DS units should be performed under Monitored Anesthesia Care (MAC).
PATIENTS AND METHODS: 960 patients underwent IH repairs over a period of 24 months. The patients were randomly divided into two groups: R (remifentanil) and F (fentanyl); the group F was considered as a control group. The exclusion criteria in both group were: morbid obesity (BMI>40 or BMI>35 in association with high blood pressure or diabetes); coagulopathy; OSAS (obstructive sleep apnea syndrome) with AHI >10; cardiovascular, respiratory, renal, hepatic or metabolic disease; history of substances abuse; GERD-related esophagitis (gastro-esophageal reflux disease); chronic analgesic use; allergy to local anesthetic and ASA>III. Patients reported their level of pain on a verbal numeric scale (VNS), with scores ranging from 0 to 10. For each patient systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded. The results are presented as the mean value ± standard deviations; statistical analysis was performed using Student's t-test.
RESULTS: Amongst the 960 procedures, complications or side effects related to the anesthetic techniques didn't occur; no procedure-related complications requiring mechanical ventilation support were reported. Our research focused on evaluating remifentanil effectiveness in pain control and its impact on hemodynamic stability and respiratory function. There was a significant difference between the two groups with regard to the VNS.
CONCLUSIONS: Remifentanil, is an excellent drug for pain control during intra-operative procedures, that allows an optimal hemodynamic stability for IH repairs in a DS setting, due to its pharmacokinetic and pharmacodynamic properties and few adverse effects.
PMID: 29442057 [PubMed - in process]
http://ift.tt/2Evov5k
The open abdomen - still a challenge for the surgeons. Which is the best technique for temporary abdominal closure? A focus on negative pressure wound therapy.
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The open abdomen - still a challenge for the surgeons. Which is the best technique for temporary abdominal closure? A focus on negative pressure wound therapy.
G Chir. 2017 Nov-Dec;38(6):267-272
Authors: Popivanov G, Kjossev K, Mutafchiyski V
PMID: 29442056 [PubMed - in process]
http://ift.tt/2CoXE4S
Transcriptional and epigenetic regulation of innate-like T lymphocyte development
Mihalis Verykokakis | Barbara L Kee
http://ift.tt/2Hh1Sz8
Chemical sensing in development and function of intestinal lymphocytes
Luisa Cervantes-Barragan | Marco Colonna
http://ift.tt/2GgcHjF
A new model for chronic diseases
Publication date: Available online 15 February 2018
Source:Medical Hypotheses
Author(s): S.D. Sara Diani
Chronic diseases are defined diseases whose symptoms last for at least six months and tend to worsen over time. In Europe, they cause at least 86% of deaths.In this speculative unifying model I set a new hypothesis for the etiology of the majority of chronic diseases. The main aim is to put order and observe our organism in a systemic way, connecting pathologies we now see as disconnected phenomena, with the conceptual frameworks of complex systems and network medicine.Chronic diseases could be caused by a first unsolved acute infection. In case the pathogen cannot be completely eliminated, it becomes a persistent infectious. After the acute episode, some mild symptoms will occur and probably disappear; the chronic disease will remain latent over time. It will manifest even after years or decades, in the presence of another acute infection, a particular stress, trauma, or another event. The presence of the persistent infectious elicits changes in the immune and systemic regulation, and these processes degenerate over time. They will assume their rules and patterns, being independent from the initial stimulus. The key to understand the dynamics and individuality of chronic diseases is the immune system and its networks. The immune mechanisms that can lead to the persistent response are mainly the switch from the Th1 to the Th2 immunity and the molecular mimicry.The first persistent infectious will also modify the susceptibility to other pathogens, facilitating new infections and new consequent persistent infectious.From the immune point of view, our organism is divided into three compartments: the outer one, which comprehend all the surfaces in contact with the environment, the intermediate one, which comprehend the internal organs and tissues, and the innermost one, comprehending the Central Nervous System and the adluminal compartment of the seminiferous tubule. The immune key-role is played respectively by the mucosa-associated lymphoid tissue, the endothelium, the blood-brain barrier and blood-testis barrier. The chronic diseases follow a progressive scheme, involving the three compartments from the outer to the innermost one.The primer microorganism at the origin of the majority of diseases could be streptococcus, or staphylococcus. Both cause acute in children, with a great variability of responses and symptoms, and both cause molecular mimicry.This model can be tested and proved in more ways, I propose here some of them.It could pave the way to a radical change in our comprehension and therapeutic approaches to chronic diseases.
http://ift.tt/2EuD6hw
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.
http://ift.tt/2CorLJC
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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Granulomatosis With Polyangiitis
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Addition to Funding/Support
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Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia
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Hypercoagulability and Severe Obstructive Sleep Apnea
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Missing Acknowledgment
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Age-Related Hearing Loss, Cognitive Function, and Dementia
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Prevalence of Laryngeal Cleft in Patients With Esophageal Atresia
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Asymptomatic Septal Mass
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Traumatic Tympanic Membrane Perforations Diagnosed in Emergency Departments
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Cerebrospinal Fluid Rhinorrhea and a Lytic-Appearing Lesion
http://ift.tt/2j1XUzz
Association of GERD With Cancer of the Upper Aerodigestive Tract in Elderly Patients
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Hypercoagulability and Severe Obstructive Sleep Apnea—Reply
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Outcomes Following Cordotomy by Coblation for Bilateral Vocal Fold Immobility
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Errors in Figures 1, 2, and 3
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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.http://ift.tt/2ELDd7s
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).
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3D Endoscopic Donor Nephrectomy Versus Robot-Assisted Donor Nephrectomy: a Detailed Comparison of 2 Prospective Cohorts
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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.
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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 (TVQMtF) 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.
http://ift.tt/2C0q7SY
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.
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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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