The differentiation of an organism into a male or female phenotype is a critical developmental process, but the mechanisms that control this decision are remarkably evolutionarily labile. This Review discusses the wide diversity of vertebrate sex-determination mechanisms, their rapid evolution under different forms of genetic and environmental control and the over-arching principles that are shared despite this mechanistic diversity.
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Κυριακή 13 Αυγούστου 2017
Vertebrate sex determination: evolutionary plasticity of a fundamental switch
The interplay of epigenetic marks during stem cell differentiation and development
Cell state transitions during embryonic development are associated with epigenetic changes that alter chromatin structure and gene expression. Interplay between epigenetic regulatory layers can be studied using genomic technologies and embryonic stem cell cultures that reflect in vivo cell states.
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Settling the score: variant prioritization and Mendelian disease
For clinical cases of Mendelian disease that lack a genetic diagnosis, genome and exome sequencing are increasingly used for seeking the genetic cause. This Review discusses the strategies and computational tools for prioritizing the many genetic variants identified in each genome into those that are most likely to be causal for disease. The authors discuss how diverse types of biochemical, evolutionary, pedigree and clinical-phenotype information are used, and they highlight common pitfalls to be aware of for responsible variant prioritization.
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20Q: Cochlear Synaptopathy - Interrupting Communication from Ear to Brain
An overview of cochlear synaptopathy based on new insights from animal studies of noise-induced and age-related hearing loss, with implications for audiology practice.
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Using endoscopy to locate the round window membrane during cochlear implantation: Our experience with 25 patients
Abstract
Locating the round window membrane during cochlear implantation surgery is crucial to insert the electrode array correctly and to minimize intracochlear damage. However, it can be difficult to access the round window membrane in certain patients, especially in paediatric patients or patients with inner ear malformations. Recently, it has been demonstrated that endoscopy enables excellent visualization and exploration of the round window niche in ear surgery.
This article is protected by copyright. All rights reserved.
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Using endoscopy to locate the round window membrane during cochlear implantation: Our experience with 25 patients
Abstract
Locating the round window membrane during cochlear implantation surgery is crucial to insert the electrode array correctly and to minimize intracochlear damage. However, it can be difficult to access the round window membrane in certain patients, especially in paediatric patients or patients with inner ear malformations. Recently, it has been demonstrated that endoscopy enables excellent visualization and exploration of the round window niche in ear surgery.
This article is protected by copyright. All rights reserved.
http://ift.tt/2w50mNI
Stratification of astrocytes in healthy and diseased brain
Abstract
Astrocytes, a subtype of glial cells, come in variety of forms and functions. However, overarching role of these cell is in the homeostasis of the brain, be that regulation of ions, neurotransmitters, metabolism or neuronal synaptic networks. Loss of homeostasis represents the underlying cause of all brain disorders. Thus, astrocytes are likely involved in most if not all of the brain pathologies. We tabulate astroglial homeostatic functions along with pathological condition that arise from dysfunction of these glial cells. Classification of astrocytes is presented with the emphasis on evolutionary trails, morphological appearance and numerical preponderance. We note that, even though astrocytes from a variety of mammalian species share some common features, human astrocytes appear to be the largest and most complex of all astrocytes studied thus far. It is then an imperative to develop humanized models to study the role of astrocytes in brain pathologies, which is perhaps most abundantly clear in the case of glioblastoma multiforme.
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Protein astrogliopathies in human neurodegenerative diseases and aging
Abstract
Neurodegenerative diseases are characterized by progressive dysfunction and loss of neurons associated with depositions of pathologically altered proteins showing hierarchical involvement of brain regions. The role of astrocytes in the pathogenesis of neurodegenerative diseases is explored as contributors to neuronal degeneration or neuroprotection pathways, and also as potential mediators of the transcellular spreading of disease-associated proteins. Protein astrogliopathy (PAG), including deposition of amyloid-β, prion protein, tau, α-synuclein, and very rarely transactive response DNA-binding protein 43 (TDP-43) is not unprecedented or unusual in neurodegenerative diseases. Morphological characterization of PAG is considered, however, only for the neuropathological diagnosis and classification of tauopathies. Astrocytic tau pathology is seen in primary frontotemporal lobar degeneration (FTLD) associated with tau pathologies (FTLD-Tau), and also in the form of aging-related tau astrogliopathy (ARTAG). Importantly, ARTAG shares common features with primary FTLD-Tau as well as with the astroglial tau pathologies that are thought to be hallmarks of a brain injury-related tauopathy known as chronic traumatic encephalopathy (CTE). Supported by experimental observations, the morphological variability of PAG might reflect distinct pathogenic involvement of different astrocytic populations. PAG might indicate astrocytic contribution to spreading or clearance of disease-associated proteins, however, this might lead to astrocytic dysfunction and eventually contribute to the degeneration of neurons. Here, we review recent advances in understanding ARTAG and other related forms of PAG.
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Diversity of astroglial responses across human neurodegenerative disorders and brain aging
Abstract
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease. Reactive astrocytosis secondary to neuron loss and astrocytopathy due to intrinsic alterations of astrocytes occur in neurodegenerative diseases, overlap each other, and, together with astrocyte senescence, contribute to disease-specific astrogliopathy in aging and neurodegenerative diseases with abnormal protein aggregates in old age. In addition to the well-known increase in glial fibrillary acidic protein and other proteins in reactive astrocytes, astrocytopathy is evidenced by deposition of abnormal proteins such as β-amyloid, hyper-phosphorylated tau, abnormal α-synuclein, mutated huntingtin, phosphorylated TDP-43 and mutated SOD1, and PrPres, in Alzheimer's disease, tauopathies, Lewy body diseases, Huntington's disease, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease, respectively. Astrocytopathy in these diseases can also be manifested by impaired glutamate transport; abnormal metabolism and release of neurotransmitters; altered potassium, calcium and water channels resulting in abnormal ion and water homeostasis; abnormal glucose metabolism; abnormal lipid and, particularly, cholesterol metabolism; increased oxidative damage and altered oxidative stress responses; increased production of cytokines and mediators of the inflammatory response; altered expression of connexins with deterioration of cell-to-cell networks and transfer of gliotransmitters; and worsening function of the blood brain barrier, among others. Increased knowledge of these aspects will permit a better understanding of brain aging and neurodegenerative diseases in old age as complex disorders in which neurons are not the only players.
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How to Work Your Way to Self-made Professional Success: Start a Business Today!
In this modern day and age, just about anyone can find success for themselves. Lack of post-secondary education or not belonging to an influential family are no longer things that hold you back from leading ...
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Comparison of the ability of esCCO and Volume View to measure trends in cardiac output in patients undergoing cardiac surgery
BACKGROUND: Cardiac output (CO) is a physiological variable that should be monitored during cardiac surgery. The purpose of this study was to assess the trending ability of two CO monitors, esCCO (Nihon Kohden™, Tokyo, Japan) and Volume View (VV) (Edwards Lifesciences, Irvine, USA).
METHODS: A total of 19 patients were included in the study. Before cardiopulmonary bypass (CPB), CO was measured simultaneously using both esCCO and VV devices before and after three CO-modifying manoeuvres (passive leg raise [PLR], the end expiratory occlusion test [EEOT] and positive end expiratory pressure [PEEP] at 10 cm H2O). Five CO values for esCCO and three for VV were averaged and compared during a one-minute period of time before and after each manoeuvre.
RESULTS: A total of 114 paired readings were collected. Median CO values were 4.3 L min-1 (IQR: 3.8; 5.2) and 3.8 L min-1 (IQR: 3.5; 4.5) for esCCO and VV, respectively. The precision error was 1.4% (95% CI:1.0–1.7) for esCCO and 2.2% (95% CI: 1.8–2.7) for VV. The bias between esCCO and VV values was normally distributed (P = 0.0596). Between esCCO and VV, the mean bias was +0.6 L min-1 with a Limit of Agreement (LOA) of –1.8 L min-1 and +3.0 L min-1. The concordance rate was 43% (95% CI: 29–58) between esCCO and VV.
CONCLUSION: Both single and trended measurements of CO using esCCO and VV were not in agreement. This large discrepancy leads one to the conclusion that any outcome study conducted with one of these devices cannot be applied to the other.
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Thermoregulation disorders of central origin — how to diagnose and treat
Fever is a common symptom in the Intensive Care Unit. At least half of febrile episodes are caused by infection. Excluding infectious etiology and other non-infectious causes of fever, especially in patients with central nervous system (CNS) disorders, attention should be paid to disturbances of thermoregulatory centre. In particular, subarachnoid haemorrhage, cerebral trauma, along with ischaemic or haemorrhagic stroke are strongly associated with the development of central fever. Proper, speedy diagnosis of the cause of fever makes it possible to implement preventive measures against the harmful effects of hyperthermia on the CNS and to avoid the consequences of inappropriate treatment. The aim of this review is to present the current treatment options for the management of central fever and to analyze recent recommendations for the treatment of hyperthermia, including the use of hypothermia. The recommendations of American and European associations are inconsistent, mainly due to the lack of randomized clinical trials confirming the effectiveness of such treatment. The diagnosis of central fever is still made by the exclusion of other causes. The authors of the review intended to present the characteristic features of central fever, differentiating this state from infectious fever and also analyze the presence of central fever in particular neurological diseases. It seems particularly important to establish diagnostic criteria for central fever or to find diagnostic markers. It is also necessary to conduct further randomized clinical trials evaluating the indications for treatment of hyperthermia.
http://ift.tt/2wW80XT
Electrical impedance tomography for diagnosis and monitoring of pulmonary function disorders in the intensive care unit — case report and review of literature
The aim of this paper is to describe the possibility of using Electrical Impedance Tomography (EIT) as a treatment monitoring tool in the ICU. It was based on case report and literature review. A 19-year-old female was admitted to ICU due to severe acute respiratory distress syndrome. Despite aggressive treatment there was no improvement. We decided to use EIT in the monitoring of treatment because of difficulties in transporting the patient to the radiology department in order to perform a control CT scan. After identifying the causing factor (Pneumocyctis jiroveci), EIT monitoring was maintained to assess the effectiveness of targeted microbial treatment. In the following days, we observed an improvement of regional ventilation of the upper and middle segments of the left lung that corresponded well with laboratory test results, especially arterial blood gas analysis. The use of Electrical Impedance Tomography enables non-invasive, bedside, continuous assessment of regional lung ventilation. It is possible to use it in both mechanically ventilated and spontaneously breathing patients. It allows efficient and dynamic monitoring of the course of the therapeutic process. Interpretation of the results is relatively easy to learn and does not require specialist knowledge. Moreover, it is possible to use EIT in those cases where other methods are of high risk or contraindicated.
http://ift.tt/2w2gFeS
Neutrophils, NETs, NETosis — old or new factors in sepsis and septic shock?
Neutrophils are an key part of the innate immune system in the host's defences against pathogens. Circulating neutrophils are recruited at the sites of infection or sterile inflammation in response to pathogen and host-derived inflammatory mediators. In addition to phagocytosis and degranulation, neutrophils display the release of NETs in order to restrain infection. NETs are able to entrap and kill microbes, and display proinflammatory and prothrombotic properties.
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Benefits of ultrasound-guided transversus abdominis plane block for open appendectomy in children
BACKGROUND: One of the most frequently performed emergency surgical procedures in children is an appendectomy. The aim of this study was to determine the benefits of supplementing standard, general anaesthesia with the ultrasound-guided right TAP block.
METHODS: We analyzed the medical records of 90 children of both sexes, aged 4–16 years with a body mass of 16–78 kg who underwent general anaesthesia for open appendectomy. Sixty-two individuals were anaesthetized using the standard method, while 28 patients had an additional right-sided TAP block under ultrasound guidance. Subsequently these groups were divided into 2 subgroups: children under 8 years and those older. We evaluated the total consumption of opioids, intraoperative fentanyl requirement, the amount of non-opioid analgesic and antiemetic drugs used during the whole hospitalization, time to recovery of digestive track function and length of hospital stay.
RESULTS: TAP block performed under USG guidance reduced the overall consumption of opioids (0.36 vs. 0.42 mg kg-1, P = 0.048), significantly shortened time of fasting after the surgery (17 vs. 29 hours, P = 0.003) as well as reduced the need for antiemetic drugs: ondansetron were used only in 21.4% of children in the group with TAP block vs. 38.7% of children with standard protocol. Additionally, we noted that the application of the TAP block shortened the length of hospitalization (3 vs. 4 days, P = 0.045).
CONCLUSION: The application of the TAP block, as a supplementary treatment to standard general anaesthesia for open appendectomy in children is a valuable component of multimodal analgesia, which might improve the quality of life of the patient and shorten the length of hospitalization.
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Impact of absence of critical respiratory rate change on oxygen desaturation following tracheal extubation after general anaesthesia: a propensity score-matched analysis
BACKGROUND: It has been suggested that oxygen desaturation may be paradoxically related to the absence of an abnormal respiratory rate (RR) during acoustic respiratory rate (RRa) monitoring in a postoperative setting. We retrospectively compared the incidence of desaruration in patients without an abnormal RR with that in patients with an abnormal RR using propensity scorer matching. We also explored the factors contributing to oxygen desaturation without an RR monitoring alert.
METHODS: We used ≤ 8 h postoperative data of the first 935 patients. Outcomes of patients with and without critical RR changes (RR > 30 or < 8 beats per min for > 2 min) (critical RR change vs. noncritical RR change) were first compared according to oxygen desaturation levels (SpO2< 90% for > 10 s). Multivariate analysis was used to determine oxygen desaturation-associated explanatory factors.
RESULTS: Propensity score matching yielded 259 patients without critical RR changes and 259 patients with critical RR changes, respectively. Oxygen desaturation rates were higher in patients without critical RR changes [noncritical RR change vs. critical RR change: 39/220 (15.1%) vs. 16/243 (6.2%)]. An odds ratio and 95% CI for the noncritical RR change was 2.56 (1.38–4.55, P = 0.002). A critical change in the RRa was not observed in 576 patients; of these, oxygen desaturation was observed in 76 (13.2%) patients. Surgery duration (OR, 1.018 per 10 min increase; 95% CI, 1.002 to 1.035) was independently associated with oxygen desaturation without critical RR change.
CONCLUSION: Postoperative oxygen desaturation paradoxically occurred more frequently in patients without critical RR changes, whose RR was monitored by the RRa under oxygen therapy. The duration of surgery may explain the possibility of postoperative oxygen desaturation without an RRa device alert.
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Sensitivity and specificity of urinalysis samples in critically ill patients
BACKGROUND: Pre-emptive screening of urine for patients admitted to an intensive care unit can result in the misinterpretation of data and over- or under-treatment of urinary tract infection.
METHODS: Data were studied from 169 consecutive patients admitted to the neurologic or burn intensive care unit at Shands Hospital at the University of Florida. All patients had a urinary catheter in place at the time of admission. Urinalysis and urine culture were sent for analysis. Data included leukocyte esterase, urine nitrate, urine protein, pyuria or urine white blood cell count, and culture.
RESULTS: Leukocyte esterase and pyuria were the most sensitive indicators of a positive urine culture at 87.5% (95% CI: 71.3–100%) and 73.3% (95% CI: 51.0–95.7%), respectively; urine nitrate was specific at 100%. More than half of the patients (56.3%) with positive cultures did not initially receive antibiotics.
CONCLUSION: The combination of leukocyte esterase and urine nitrate provides the best indicator for the initiation of antibiotic coverage for urinary tract infection prior to culture availability.
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Evaluation of a low-cost, 3D-printed model for bronchoscopy training
BACKGROUND: Flexible bronchoscopy is a fundamental procedure in anaesthesia and critical care medicine. Although learning this procedure is a complex task, the use of simulation-based training provides significant advantages, such as enhanced patient safety. Access to bronchoscopy simulators may be limited in low-resource settings. We have developed a low-cost 3D-printed bronchoscopy training model.
METHODS: A parametric airway model was obtained from an online medical model repository and fabricated using a low-cost 3D printer. The participating physicians had no prior bronchoscopy experience. Participants received a 30-minute lecture on flexible bronchoscopy and were administered a 15-item pre-test questionnaire on bronchoscopy. Afterwards, participants were instructed to perform a series of predetermined bronchoscopy tasks on the 3D printed simulator on 4 consecutive occasions. The time needed to perform the tasks and the quality of task performance (identification of bronchial anatomy, technique, dexterity, lack of trauma) were recorded. Upon completion of the simulator tests, participants were administered the 15-item questionnaire (post-test) once again. Participant satisfaction data on the perceived usefulness and accuracy of the 3D model were collected. A statistical analysis was performed using the t-test. Data are reported as mean values (± standard deviation).
RESULTS: The time needed to complete all tasks was 152.9 ± 71.5 sec on the 1st attempt vs. 98.7 ± 40.3 sec on the 4th attempt (P = 0.03). Likewise, the quality of performance score improved from 8.3 ± 6.7 to 18.2 ± 2.5 (P < 0.0001). The average number of correct answers in the questionnaire was 6.8 ± 1.9 pre-test and 13.3 ± 3.1 post-test (P < 0.0001). Participants reported a high level of satisfaction with the perceived usefulness and accuracy of the model.
CONCLUSIONS: We developed a 3D-printed model for bronchoscopy training. This model improved trainee performance and may represent a valid, low-cost bronchoscopy training tool.
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Do bacteria isolated from ICU patients ‘ESKAPE’ antibiotic treatment? In vitro susceptibility of the Enterobacteriaceae family to tigecycline
Background: Enterobacteriaceae are currently causing the majority of healthcare-associated infections (HAI) and
simultaneously expressing increasing levels of antibiotic resistance. The purpose of this study is to assess the in vitro
sensitivity of MDR strains from the family Enterobacteriaceae to tigecycline in relation to their origin from patients
hospitalized in intensive care units (ICUs) and non-ICUs.
Methods: The study involved 156 clinically significant strains of the Enterobacteriaceae family isolated from patients
with complicated intraabdominal infections (cIAIs) and/or complicated skin and skin structure infections (cSSSIs)
hospitalized in ICUs and other surgical departments. Tigecycline MICs were determined by Etest.
Results: The highest percentage of tigecycline non-susceptible (intermediate + resistant strains) in vitro strains
among the Enterobacteriaceae species were observed for Serratia spp. 77.3%, followed by Citrobacter spp. (76.9%)
and Enterobacter spp. (70%); whereas K. pneumoniae and E. coli showed 73–73.8% tigecycline susceptibility rates.
Conclusion: Tigecycline demonstrates a high level of antimicrobial in vitro activity when tested against E. coli and
K. pneumoniae, even those with the ESBL-phenotype. Tigecycline retained activity against merely 22–30% of Enterobacter, Citrobacter and Serratia genera.
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Randomised controlled trial of analgesic effectiveness of three different techniques of single-shot interscalene brachial plexus block using 20 mL of 0.5% ropivacaine for shoulder arthroscopy
BACKGROUND: Shoulder arthroscopic procedures impose a challenge to anaesthesiologists in terms of postoperative analgesia. Proper pain management after arthroscopic procedures improves patient satisfaction and facilitates early rehabilitation.
METHODS: We performed a randomized, prospective clinical study to assess the influence of anthropometric parameters and IBPB technique on the quality of postoperative analgesia. A total of 106 randomly selected patients of ASA I–III status scheduled for elective shoulder arthroscopy. Reasons for exclusion were neurological deficit in the upper arm, allergies to amide-type local anesthetics, coagulopathy, and pregnancy.The patients received 20 mL of 0.5% ropivacaine for an ultrasound-guided interscalene brachial plexus block (IBPB) (group U), peripheral nerve stimulation (PNS)-confirmed IBPB (group N), or ultrasound-guided, PNS-confirmed IBPB (dual guidance; group NU).
RESULTS: We observed that the three groups did not differ in mean time of sensory and motor block terminations. In individual cases in each group, sensory block lasted up to 890–990 minutes, providing satisfactory long lasting postoperative analgesia in patients receiving IBPB. We observed a negative correlation between body mass index and termination of motor block (P = 0.037, Pearson's correlation coefficient) and a positive correlation between age and termination of sensory block (P = 0.0314, Pearson's correlation coefficient) in group U compared to the other two groups. We found a positive correlation between male gender and termination of motor block (P = 0.0487, Pearson's correlation coefficient) in group N compared to the other two groups.
CONCLUSION: In our study, patients received satisfactory analgesia in the postoperative period regardless of technique used, age, gender, or potentially uncommon anthropometry.
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Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer
Source:Radiotherapy and Oncology
Author(s): O. Bohoudi, A.M.E. Bruynzeel, S. Senan, J.P. Cuijpers, B.J. Slotman, F.J. Lagerwaard, M.A. Palacios
Background and purposeTo implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC).Material and methodsSMART strategy for plan adaptation was implemented with the MRIdian system (ViewRay Inc.). At each fraction, OAR (re-)contouring is done within a distance of 3cm from the PTV surface. Online plan re-optimization is based on robust prediction of OAR dose and optimization objectives, obtained by building an artificial neural network (ANN). Proposed limited re-contouring strategy for plan adaptation (SMART3CM) is evaluated by comparing 50 previously delivered fractions against a standard (re-)planning method using full-scale OAR (re-)contouring (FULLOAR). Plan quality was assessed using PTV coverage (V95%, Dmean, D1cc) and institutional OAR constraints (e.g. V33Gy).ResultsSMART3CM required a significant lower number of optimizations than FULLOAR (4 vs 18 on average) to generate a plan meeting all objectives and institutional OAR constraints. PTV coverage with both strategies was identical (mean V95%=89%). Adaptive plans with SMART3CM exhibited significant lower intermediate and high doses to all OARs than FULLOAR, which also failed in 36% of the cases to adhere to the V33Gy dose constraint.ConclusionsSMART3CM approach for LAPC allows good OAR sparing and adequate target coverage while requiring only limited online (re-)contouring from clinicians.
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Ameloblastic Fibroodontoma: Uncommon Case Presentation in a 6-Year-Old Child with Review of the Literature
Ameloblastic fibroodontoma is a benign mixed odontogenic neoplasm considered in patients with asymptomatic swelling and unerupted teeth that exhibit histologic features between ameloblastic fibroma and complex odontoma. Radiographically, this lesion appears as radiolucency admixed with focal radio opaque masses of irregular shapes and sizes. This lesion is confirmed by the presence of proliferating odontogenic epithelium, ectomesenchyme, and dental hard tissue formation on pathological analysis supplementing clinical and radiographic findings. As this tumour is less commonly seen in routine clinical practice, ameloblastic fibroodontoma with detailed orofacial features and periodic approach to its diagnosis is discussed. This paper reports a case of ameloblastic fibroodontoma of the mandible in a 6-year-old male patient with an uncommon case presentation and review of the literature.
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Severe Hepatopulmonary Syndrome in a Child with Caroli Syndrome
Hepatopulmonary Syndrome (HPS) is a potential complication of chronic liver disease and is more commonly seen in the adult population. Caroli Syndrome is a rare inherited disorder characterized by intrahepatic ductal dilation and liver fibrosis that leads to portal hypertension. In children with liver disease, HPS should be considered in the differential diagnosis of prolonged, otherwise unexplained, hypoxemia. The presence of HPS can improve patient priority on the liver transplantation wait list, despite their Pediatric End-Stage Liver Disease (PELD) score. We present a 6-year-old girl with Caroli Syndrome and End-Stage Renal Disease who presented with persistent hypoxemia. The goal of this report is to increase awareness of HPS in children.
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Quantitative Evaluation of Head and Neck Cancer Treatment-Related Dysphagia in the Development of a Personalized Treatment De-Intensification Paradigm
Publication date: Available online 12 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Harry Quon, Xuan Hui, Zhi Cheng, Scott Robertson, Luke Peng, Michael Bowers, Joseph Moore, Amanda Choflet, Alex Thompson, Mariah Muse, Ana Kiess, Brandi Page, Carole Fakhry, Christine Gourin, Jolyne O'Hare, Peter Graham, Michal Szczesniak, Julia Maclean, Ian Cook, Todd McNutt
ObjectiveWe hypothesize that quantifying swallow function with multiple patient-reported outcome (PRO) instruments is an important strategy to yield insights in the development of personalized de-intensified therapies seeking to reduce the risk of head and neck cancer treatment-related dysphagia (HNCTD).MethodsIrradiated HNC subjects seen in follow-up care (4/2015 to 12/2015) prospectively completed the Sydney Swallow Questionnaire (SSQ) and the MD Anderson Dysphagia Inventory (MDADI) concurrently on the web-interface to our Xxxxxxxxx database were evaluated. A correlation matrix quantified the relationship between the SSQ and MDADI. Machine-learning unsupervised cluster analysis using the elbow criterion and CLUSPLOT analysis to establish its validity was performed.ResultsWe identified 89 subjects. The MDADI and SSQ scores were moderately but significantly correlated (correlation coefficient -0.69). K-means cluster analysis demonstrated that three unique statistical cohorts (elbow criterion) could be identified with CLUSPLOT analysis confirming that 100% of variances were accounted. Correlation coefficients between the individual items in the SSQ and the MDADI demonstrated weak to moderate negative correlation except for SSQ17 (QoL question).ConclusionsPilot analysis demonstrates the MDADI and SSQ are complementary. Three unique clusters of patients can be defined suggesting that a unique dysphagia signature for HNCTD may be definable. Longitudinal studies relying on only a single PRO such as MDADI may be inadequate for classifying HNCTD.
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Long-term clinical outcomes of Pencil Beam Scanning Proton Therapy for benign and non-benign intracranial meningiomas
Publication date: Available online 12 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Fritz R. Murray, James W. Snider, Alessandra Bolsi, Antony J. Lomax, Marc Walser, Ulrike Kliebsch, Ralf A. Schneider, Damien C. Weber
Since 1996, 96 patients with complex intracranial meningiomas have been treated with pencil beam scanning proton therapy (PBSPT) at XXXX. The long-term results of the present study demonstrate PBSPT as an effective and safe treatment modality for the definitive, adjuvant, postoperative, and salvage treatment of highly complex intracranial meningiomas. In addition, multiple risk factors influencing local control and overall survival were identified.
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Elevated IL-31 serum levels in bullous pemphigoid patients correlate with eosinophil numbers and are associated with BP180-IgE
Publication date: Available online 12 August 2017
Source:Journal of Dermatological Science
Author(s): Mareen Salz, Stefanie Haeberle, Jochen Hoffmann, Alexander H. Enk, Eva N. Hadaschik
http://ift.tt/2wFRcoB
9-phenanthrol enhances the generation of an CD8+ T cell response following transcutaneous immunization with imiquimod in mice
Publication date: Available online 12 August 2017
Source:Journal of Dermatological Science
Author(s): Ann-Kathrin Hartmann, Pamela Aranda Lopez, Marek Zajac, Marc Freichel, Hansjörg Schild, Markus P. Radsak, Michael Stassen
BackgroundTranscutaneous immunization (TCI) is a non-invasive vaccination strategy targeting the skin-associated lymphoid tissue. Topical application of the TLR7 agonist imiquimod as adjuvant in combination with peptide antigens activates the innate immune system and mounts cytotoxic T lymphocyte (CTL) responses.ObjectiveBased on the commercial 5% imiquimod-containing drug Aldara we aimed to develop an improved formulation with superior vaccination efficiencies. The primary target was the enhancement of mast cell activation as important key for the function of the innate immune system.MethodsWe investigated the effects of 9-phenanthrol (9-phe) on the activation of mast cells in vitro and in vivo. For TCI, we applied 0.2% 9-phe in Aldara or Aldara alone as adjuvants in combination with the MHC class I − restricted peptide SIINFEKL. To monitor vaccination, mast cell degranulation, migration of DC and frequencies of epitope-specific CTL was assessed. In a transgenic tumor model, the efficiencies of prophylactic immunization against a tumor antigen were also monitored.Results9-phe induced degranulation of mast cells in vitro and upon topical application in vivo. A mixture of 0.2% 9-phe in Aldara showed superior results regarding the migration of DC and the expansion of antigen-specific CTL. Consequently, prophylactic immunization with 0.2% 9-phe in Aldara caused enhanced protection against tumor inoculation.ConclusionOur data demonstrate that a simple modification of an adjuvant formulation can yield superior results in experimental vaccination protocols by boosting critical steps leading to the generation of an efficient CTL response.
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Domains in mixtures of amphiphilic macromolecules with different stiffness of backbone
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Mikhail K. Glagolev, Valentina V. Vasilevskaya, Alexei R. Khokhlov
The domain structuring in concentrated mixtures of amphiphilic macromolecules with a different stiffness of backbone has been discovered and studied by means of molecular dynamics simulation. The macromolecules were composed of identical amphiphilic H-graft-P monomer units. In flexible macromolecules, the H-graft-P units are connected freely, whereas the stiff macromolecules have limitations imposed on torsion and bending angles and carry local helical structure. In solvent which is poor for the backbone, stiff macromolecules form filament clusters from few intertwined helical chains. The filaments can be aligned along each other sharing a common director or form a few liquid-crystalline domains oriented randomly with respect to each other. It was shown that increase of fraction of helical macromolecules leads to decrease of order parameter and its high variation over different samples due to the increase of length and polydispersity of persistent filaments.
Graphical abstract
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Watching shear thinning in creep: Entanglement-disentanglement transition
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Sirui Ge, Xiangyang Zhu, Shi-Qing Wang
We have carried out various rheometric experiments to probe the nonlinear rheological behavior of two well-entangled 1,4-polybutadiene solutions using both stress-controlled and rate-controlled startup shear. At a polymer concentration of 2% neither wall slip nor shear banding occurs, and there is no visible edge failure. At a moderate level of shear stress, the shear rate can take an induction time tind longer than the reptation time to rise toward an eventual steady-state value. The time tind for the entanglement-distanglement transition (EDT) shortens exponentially with increasing stress. The state of entanglement also changes in response to a sinusoidal stress σ0sinωt when its amplitude σ0 is beyond a threshold to produce a sufficiently high strain amplitude γ0 (>1). Moreover, the evolution of the state of chain entanglement during and after constant-stress creep has been studied using two different protocols. The first switches from creep to rate-controlled startup shear to determine the stress overshoot characteristic. In the second protocol, after creep to different stages, the sample is evaluated for its ability to undergo elastic recovery. We found that the overshoot response to the rate switching weakens and the ability to undergo elastic recoil deteriorates as the EDT progresses. These changes are clearly inherent because edge instability could not produce such effects. Thus, it is confirmed that an entanglement-disentanglement transition is a leading characteristic rheological response of these solutions.
Graphical abstract
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Furan-functionalized aniline trimer based self-healing polymers exhibiting high efficiency of anticorrosion
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Tsai-Wei Chuo, Ying-Ling Liu
An aniline trimer derivative possessing multiple furan groups (TFAT) is prepared and used as a building unit for preparation of self-healing anticorrosion coatings. The aniline trimer unit brings electrochemical activity to TFAT, and the tertiary amine and glycidylether groups provide TFAT excellent adhesive ability. Both features contribute to the high performance of anticorrosion property of crosslinked TFAT coatings on cold-rolled steel (CRS). An ultralow corrosion rate of 0.12 μm y−1 and a high impedance at low frequency (Z0) of 9.2 × 105 Ω cm−2 have been recorded with the coatings, both demonstrate hundreds times enhancements of the anticorrosion properties compared to the CRS samples coated with crosslinked aniline trimer (corrosion rate: 71 μm y−1; Z0: 1240 Ω cm−2). Moreover, as possessing furan groups, TFAT is a suitable agent to react with multifunctional maleimide compounds for formation of thermally-reversible crosslinked networks through Diels-Alder reaction. Consequently, TFAT-based self-healing anticorrosion coatings are obtained. In a cycle test, the TFAT-based reversible crosslinked coating demonstrates a high self-healing efficiency of anticorrosion with a recovery of protection efficiency from 79.8% to 99.2%, corresponding to a 99.3% of protection efficiency based recovery. A new material showing high anticorrosion and self-healing efficiency for self-healing anticorrosion coatings has been demonstrated.
Graphical abstract
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Contribution of the rigid amorphous fraction to physical ageing of semi-crystalline PLLA
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Maria Cristina Righetti, Massimo Gazzano, Nicolas Delpouve, Allisson Saiter
The physical ageing of poly(l-lactic acid) (PLLA) samples crystallized in a wide temperature range, is compared, through the analysis of the enthalpy relaxation, with the behavior of a completely amorphous sample, in the same undercooling conditions. A preliminary determination of the percentage of the different phases in the semi-crystalline samples (crystalline, mobile amorphous and rigid amorphous fractions) has been performed. The enthalpy loss (Δha), normalized to the mobile amorphous content, has allowed to differentiate PLLA samples crystallized at different temperatures, because the samples crystallized at lower temperatures, characterized by a slightly constrained mobile amorphous fraction, exhibit a smaller enthalpy loss. In addition, the normalized Δha data relative to the semi-crystalline PLLA samples have been found to deviate from the Δha values of the amorphous sample at high undercooling. This trend has been ascribed to the contribution of the rigid amorphous fraction to the structural relaxation process. The experimental data have been explained by supposing that structural relaxation in amorphous and semi-crystalline PLLA occurs at low undercooling via cooperative segmental motions, whereas, at high undercooling, through small-scale local motions, which take place also in the rigid amorphous fraction.
Graphical abstract
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Optically active microspheres from helical substituted polyacetylene with pendent ferrocenyl amino-acid derivative. Preparation and recycling use for direct asymmetric aldol reaction in water
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Jinrui Deng, Jianping Deng
The contribution reports a novel type of chiral microspheres in which ferrocenyl amino-acid derived catalytic moieties were integrated with optically active helical substituted polyacetylene. The microspheres were prepared by suspension copolymerization of achirally and chirally substituted acetylenic monomers in a quantitative yield. SEM images showed the microspheres' regular spherical morphology. Circular dichroism and UV−vis absorption spectra demonstrated that the copolymer chains constituting the microspheres adopted predominantly one-handed helices, endowing the microspheres with optical activity. The microspheres were further used to catalyze aldol reaction between cyclohexanone and p-nitrobenzaldehyde in water media in the presence of Brøsted acid, providing the product with remarkable yield (up to 91%) and enantiomeric excess (up to 93%). Synergistic effects occurred in the helical polymer chains and the pendant catalytic moieties. The catalytic microspheres can be finely recycled and reused three times without significant loss of catalytic ability and enantio-selectivity.
Graphical abstract
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Influence of electropolymerized polypyrrole optical properties on bifacial Dye-Sensitized Solar Cells
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Nicola Sangiorgi, Alessandra Sanson
In this work the effect of different doping anions on transparency, photovoltaic efficiency and interface properties of electropolymerized polypyrrole (PPy) films as counter electrode in bifacial DSSCs was study. The transparency of the counter electrode becomes relevant in order to enhance the final device efficiency and for alternative application area like of Building-Integrated Photovoltaic. PPy was prepared by electrochemical process with doping anions: chloride, perchlorate, sulfate and dodecylbenzenesulfonate. PPy doped with high concentration (0.5 M) of small anions (chloride) produced the highest transparency film (65% at 525 nm), the DSSCs with highest efficiency ratio (close to 70%) and lowest device reflectance (11%). Considering all of these results, not only the transparency of counter electrode was found to influence the efficiency of the bifacial DSSCs, but also the optical properties of PPy/electrolyte interface. This interface is probably strictly affected to the PPy morphology produced by different doping anions and the electropolymerization process used.
http://ift.tt/2w0kscz
Impact of the number of fluorine atoms on crystalline, physicochemical and photovoltaic properties of low bandgap copolymers based on 1,4-dithienylphenylene and diketopyrrolopyrrole
Publication date: 8 September 2017
Source:Polymer, Volume 125
Author(s): Guangrun Liu, Chao Weng, Pan Yin, Songting Tan, Ping Shen
Three low bandgap conjugated copolymers (PB-DPP, PDFB-DPP, and PTFB-DPP) based on 1,4-dithienylphenylene and diketopyrrolopyrrole units were synthesized and characterized as the donor materials for polymer solar cells. The effect of the number of fluorine atoms on thermodynamic, crystalline, physicochemical and photovoltaic properties of the copolymers was comparatively investigated. Results indicate that the absorption peaks of polymer solutions are blue-shifted and optical bandgaps are gradually decreased along with the increase of the number of fluorine atoms. Moreover, PDFB-DPP and PTFB-DPP show better light-harvesting abilities, higher crystallinities and lower-lying HOMO energy levels than those of PB-DPP. Photovoltaic performances of these copolymers were studied and optimized. PDFB-DPP and PTFB-DPP deliver a power conversion efficiency of 5.31% and 4.93%, respectively, both of which are higher than that of PB-DPP (4.13%) due to the increased Jsc and Voc. This work demonstrates that the number of fluorine substitution is crucial to improving optoelectronic properties.
Graphical abstract
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Protein Allergy and GMOs
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): G.S. Ladics
A rigorous safety assessment process exists for genetically modified (GM) crops. It includes an evaluation of the introduced protein as well as the crop containing such protein with the goal of demonstrating the GM crop is "as-safe-as" non-GM crops in the food supply. One of the major issues for GM crops is the assessment of the expressed protein for allergenic potential. Currently, no single factor is recognized as a predictor for protein allergenicity. Therefore, a weight-of-the-evidence approach, which takes into account a variety of factors and approaches for an overall assessment of allergenic potential, is conducted. This assessment is based on what is known about allergens, including the history of exposure and safety of the gene(s) source; protein structure (e.g., amino acid sequence identity to human allergens); stability to pepsin digestion in vitro; an estimate of exposure of the novel protein(s) to the gastrointestinal tract where absorption occurs [e.g., protein abundance in the crop, processing effects (i.e., heat stability)]; glycosylation status; and, when appropriate, specific IgE-binding studies with sera from relevant clinically allergic subjects. Since GM crops were first commercialized over 20years ago, there is no proof that the introduced novel protein(s) in any approved GM crop has caused food allergy.
http://ift.tt/2uzSPH4
Protein Allergy and GMOs
Publication date: 2017
Source:Reference Module in Biomedical Sciences
Author(s): G.S. Ladics
A rigorous safety assessment process exists for genetically modified (GM) crops. It includes an evaluation of the introduced protein as well as the crop containing such protein with the goal of demonstrating the GM crop is "as-safe-as" non-GM crops in the food supply. One of the major issues for GM crops is the assessment of the expressed protein for allergenic potential. Currently, no single factor is recognized as a predictor for protein allergenicity. Therefore, a weight-of-the-evidence approach, which takes into account a variety of factors and approaches for an overall assessment of allergenic potential, is conducted. This assessment is based on what is known about allergens, including the history of exposure and safety of the gene(s) source; protein structure (e.g., amino acid sequence identity to human allergens); stability to pepsin digestion in vitro; an estimate of exposure of the novel protein(s) to the gastrointestinal tract where absorption occurs [e.g., protein abundance in the crop, processing effects (i.e., heat stability)]; glycosylation status; and, when appropriate, specific IgE-binding studies with sera from relevant clinically allergic subjects. Since GM crops were first commercialized over 20years ago, there is no proof that the introduced novel protein(s) in any approved GM crop has caused food allergy.
http://ift.tt/2uzSPH4
Malignant Pleural Mesothelioma: State of the art and advanced cell therapy.
| Related Articles |
Malignant Pleural Mesothelioma: State of the art and advanced cell therapy.
Eur J Med Chem. 2017 Aug 02;:
Authors: Facchetti G, Petrella F, Spaggiari L, Rimoldi I
Abstract
Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy, with a response rate of 20% of patients and for this reason an efficient treatment is still a challenge. Platinum-based chemotherapy in association with a third-generation antifolate is the front-line standard of care whereas any second-line treatment was approved for MPM thus making it a pathology that evokes the need for new therapeutic agents. Different platinum-drugs were synthesised and tested as an option for patients who are not candidates to cisplatin-based therapy. Among these, monofunctional cationic antineoplastic platinum compounds received a special attention in the last decade. Alternative strategies to the commonly used combination-therapy resulted from the use of Mesenchymal Stromal Cells (MSC) widely used in the field of regenerative medicine and recently proposed as natural carriers for a selective delivery of chemotherapeutic agents and from the use of immune checkpoint and kinase inhibitors. The present short review shed light on the recent state of art and the future perspectives relative to MPM therapy.
PMID: 28800871 [PubMed - as supplied by publisher]
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Manoeuvre to aid Endoscopic division of aryepiglottic folds (Aryepiglottoplasty)
Laryngomalacia, a congenital malformation of larynx is the commonest cause of stridor in young infants. Ninety percent of cases resolve by the age of 2 years without any active intervention (1).The most consistent abnormality seen in non-resolving cases is shortening of the aryepiglottic folds (picture 1).(2)
This article is protected by copyright. All rights reserved.
http://ift.tt/2w0e6dd
Manoeuvre to aid Endoscopic division of aryepiglottic folds (Aryepiglottoplasty)
Laryngomalacia, a congenital malformation of larynx is the commonest cause of stridor in young infants. Ninety percent of cases resolve by the age of 2 years without any active intervention (1).The most consistent abnormality seen in non-resolving cases is shortening of the aryepiglottic folds (picture 1).(2)
This article is protected by copyright. All rights reserved.
http://ift.tt/2w0e6dd
Large BTK gene mutation in a child with X-linked agammaglobulinemia and polyarthritis
Source:Clinical Immunology
Author(s): Dhrubajyoti Sharma, Aman Gupta, Shubham Goel, Madhubala Sharma, Amit Rawat, Surjit Singh
http://ift.tt/2vRlvel
Large BTK gene mutation in a child with X-linked agammaglobulinemia and polyarthritis
Source:Clinical Immunology
Author(s): Dhrubajyoti Sharma, Aman Gupta, Shubham Goel, Madhubala Sharma, Amit Rawat, Surjit Singh
http://ift.tt/2vRlvel
Vitreous amyloidosis with autonomic neuropathy of the digestive tract associated with a novel transthyretin p.Gly87Arg variant in a Bangladeshi patient: a case report
Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy. Since its first description, more than 120 amyloidogeni...
http://ift.tt/2vRdndX
Vitreous amyloidosis with autonomic neuropathy of the digestive tract associated with a novel transthyretin p.Gly87Arg variant in a Bangladeshi patient: a case report
Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy. Since its first description, more than 120 amyloidogeni...
http://ift.tt/2vRdndX
Consultation for Simple Laceration Repair When On-Call in the Emergency Department: Potential Quagmire
Summary: What are the forces obligating a plastic surgeon who is on-call for the emergency department to respond to a consultation request for repair of a simple laceration? Although the duties are clear in cases of obvious surgical emergency, ambiguity and subsequent conflict may arise when the true nature of the emergency is less clear. Does the consultant's clinical discretion dictate the obligation in the case of a simple laceration; or is it subservient to either the discretion of the requesting health-care provider or even the patient? Do federal statutes such as the Emergency Medical Treatment and Labor Act, or perhaps more local rules apply, such as the by-laws of the hospital? It would behoove all medical practitioners to familiarize themselves with both the legal and moral implications of these issues. Having legitimate policies in place which actively address those situations where the consultative obligation is unclear is critical to resolve potential conflict.
http://ift.tt/2fBXjpK
http://ift.tt/2fBXjpK
Large Eyelid Defect Repair Using a Free Full-Thickness Eyelid Graft
http://ift.tt/2fCffAJ
FERM domain phosphorylation and endogenous 3′UTR are not essential for regulating the function and subcellular localization of polarity protein Crumbs
Source:Journal of Genetics and Genomics
Author(s): Haowei Cao, Rui Xu, Qiping Shi, Dandan Zhang, Juan Huang, Yang Hong
http://ift.tt/2uBQgQI
Efficient generation of the mouse model with a defined point mutation through haploid cell-mediated gene-editing
Source:Journal of Genetics and Genomics
Author(s): Leixin Wei, Xiukun Wang, Suming Yang, Wen Yuan, Jinsong Li
http://ift.tt/2w1RfNG
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