Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 12 Δεκεμβρίου 2016

Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial

Background. Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma.

Methods. Fifty hypotensive (systolic arterial pressure ≤100 mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6 g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed.

Results. Overall, 96% (43/45) [95% CI 86–99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12 h after admission with the largest difference at three h (2.9 mg dL 1 vs. 1.8 mg dL 1; P<0.01). The 28-day mortality and thromboembolic complications were similar between groups.

Conclusions. Early infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.



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Multidisciplinary management to decrease perioperative complications in senile patients with hypoxaemia in high altitudes during primary hip arthroplasty: data from our cohort study



http://ift.tt/2hvQK7Y

Time to move the goalposts? Do we need new targets for developing i.v. anaesthetics?



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The impact of the acute respiratory distress syndrome on outcome after oesophagectomy



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Ultrasound-guided posterior cord and selective suprascapular block for shoulder surgery



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The trend interchangeability method



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Glycaemic control during cataract surgery under loco-regional anaesthesia: a growing problem and we are none the wiser



http://ift.tt/2hvWNti

Trainee anaesthetist diagnosis of intraneural injection--a study comparing B-mode ultrasound with the fusion of B-mode and elastography in the soft embalmed Thiel cadaver model

Background. The incidence of intraneural injection during trainee anaesthetist ultrasound guided nerve block varies between 16% in experts and up to 35% in trainees. We hypothesized that elastography, an ultrasound-based technology that presents colour images of tissue strain, had the potential to improve trainee diagnosis of intraneural injection during UGRA, when integrated with B-Mode ultrasound onto a single image.

Methods. We recorded 40 median nerve blocks randomly allocated to 0.25 ml, 0.5 ml, 1 ml volumes to five sites, on both arms of two soft embalmed cadavers, using a dedicated B-Mode ultrasound and elastography transducer. We wrote software to fuse elastogram and B-Mode videos, then asked 20 trainee anaesthetists whether injection was intraneural or extraneural when seeing B-Mode videos, adjacent B-Mode and elastogram videos, fusion elastography videos or repeated B-Mode ultrasound videos.

Results. Fusion elastography improved the diagnosis of intraneural injection compared with B-Mode ultrasound, Diagnostic Odds Ratio (DOR) (95%CI) 21.7 (14.5 - 33.3) vs DOR 7.4 (5.2 – 10.6), P < 0.001. Compared with extraneural injection, intraneural injection was identified on fusion elastography as a distinct, brighter translucent image, geometric ratio 0.33 (95%CI: 0.16 – 0.49) P < 0.001. Fusion elastography was associated with greater trainee diagnostic confidence, OR (95%CI) 1.89 (1.69 – 2.11), P < 0.001, and an improvement in reliability, Kappa 0.60 (0.55 - 0.66).

Conclusions. Fusion elastography improved the accuracy, reliability and confidence of trainee anaesthetist diagnosis of intraneural injection.



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Cover Page



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The suffering and satisfaction of Schrödingers cat



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Evaluation of artery and vein differentiation methods using ultrasound imaging among medical students



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Effects of pneumoperitoneum and Trendelenburg position on intracranial pressure assessed using different non-invasive methods

Background. The laparoscopic approach is becoming increasingly frequent for many different surgical procedures. However, the combination of pneumoperitoneum and Trendelenburg positioning associated with this approach may increase the patient's risk for elevated intracranial pressure (ICP). Given that the gold standard for the measurement of ICP is invasive, little is known about the effect of these common procedures on ICP.

Methods. We prospectively studied 40 patients without any history of cerebral disease who were undergoing laparoscopic procedures. Three different methods were used for non-invasive estimation of ICP: ultrasonography of the optic nerve sheath diameter (ONSD); transcranial Doppler-based (TCD) pulsatility index (ICPPI); and a method based on the diastolic component of the TCD cerebral blood flow velocity (ICPFVd). The ONSD and TCD were measured immediately after induction of general anaesthesia, after pneumoperitoneum insufflation, after Trendelenburg positioning, and again at the end of the procedure.

Results. The ONSD, ICPFVd, and ICPPI increased significantly after the combination of pneumoperitoneum insufflation and Trendelenburg positioning. The ICPFVd showed an area under the curve of 0.80 [95% confidence interval (CI) 0.70–0.90] to distinguish the stage associated with the application of pneumoperitoneum and Trendelenburg position; ONSD and ICPPI showed an area under the curve of 0.75 (95% CI 0.65–0.86) and 0.70 (95% CI 0.58–0.81), respectively.

Conclusions. The concomitance of pneumoperitoneum and the Trendelenburg position can increase ICP as estimated with non-invasive methods. In high-risk patients undergoing laparoscopic procedures, non-invasive ICP monitoring through a combination of ONSD ultrasonography and TCD-derived ICPFVd could be a valid option to assess the risk of increased ICP.



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Upper trunk block: description of a supraclavicular approach of upper trunk at the points of its division



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What is the rationale for preoperative medical evaluations? A closer look at surgical risk and common terminology



http://ift.tt/2hvUJ4l

Multidisciplinary management to decrease perioperative complications in senile patients with hypoxaemia in high altitudes during primary hip arthroplasty: data from our cohort study



http://ift.tt/2hvQK7Y

Time to move the goalposts? Do we need new targets for developing i.v. anaesthetics?



http://ift.tt/2gsHe0n

Ultrasound-guided posterior cord and selective suprascapular block for shoulder surgery



http://ift.tt/2hx6K9E

Glycaemic control during cataract surgery under loco-regional anaesthesia: a growing problem and we are none the wiser



http://ift.tt/2hvWNti

Cover Page



http://ift.tt/2hvTO4d

The suffering and satisfaction of Schrödingers cat



http://ift.tt/2gsBHHl

Effects of pneumoperitoneum and Trendelenburg position on intracranial pressure assessed using different non-invasive methods

Background. The laparoscopic approach is becoming increasingly frequent for many different surgical procedures. However, the combination of pneumoperitoneum and Trendelenburg positioning associated with this approach may increase the patient's risk for elevated intracranial pressure (ICP). Given that the gold standard for the measurement of ICP is invasive, little is known about the effect of these common procedures on ICP.

Methods. We prospectively studied 40 patients without any history of cerebral disease who were undergoing laparoscopic procedures. Three different methods were used for non-invasive estimation of ICP: ultrasonography of the optic nerve sheath diameter (ONSD); transcranial Doppler-based (TCD) pulsatility index (ICPPI); and a method based on the diastolic component of the TCD cerebral blood flow velocity (ICPFVd). The ONSD and TCD were measured immediately after induction of general anaesthesia, after pneumoperitoneum insufflation, after Trendelenburg positioning, and again at the end of the procedure.

Results. The ONSD, ICPFVd, and ICPPI increased significantly after the combination of pneumoperitoneum insufflation and Trendelenburg positioning. The ICPFVd showed an area under the curve of 0.80 [95% confidence interval (CI) 0.70–0.90] to distinguish the stage associated with the application of pneumoperitoneum and Trendelenburg position; ONSD and ICPPI showed an area under the curve of 0.75 (95% CI 0.65–0.86) and 0.70 (95% CI 0.58–0.81), respectively.

Conclusions. The concomitance of pneumoperitoneum and the Trendelenburg position can increase ICP as estimated with non-invasive methods. In high-risk patients undergoing laparoscopic procedures, non-invasive ICP monitoring through a combination of ONSD ultrasonography and TCD-derived ICPFVd could be a valid option to assess the risk of increased ICP.



http://ift.tt/2gsEU9T

The Role of Categorical Speech Perception and Phonological Processing in Familial Risk Children With and Without Dyslexia

Purpose
This study assessed whether a categorical speech perception (CP) deficit is associated with dyslexia or familial risk for dyslexia, by exploring a possible cascading relation from speech perception to phonology to reading and by identifying whether speech perception distinguishes familial risk (FR) children with dyslexia (FRD) from those without dyslexia (FRND).
Method
Data were collected from 9-year-old FRD (n = 37) and FRND (n = 41) children and age-matched controls (n = 49) on CP identification and discrimination and on the phonological processing measures rapid automatized naming, phoneme awareness, and nonword repetition.
Results
The FRD group performed more poorly on CP than the FRND and control groups. Findings on phonological processing align with the literature in that (a) phonological processing related to reading and (b) the FRD group showed the lowest phonological processing outcomes. Furthermore, CP correlated weakly with reading, but this relationship was fully mediated by rapid automatized naming.
Conclusion
Although CP phonological skills are related to dyslexia, there was no strong evidence for a cascade from CP to phonology to reading. Deficits in CP at the behavioral level are not directly associated with dyslexia.

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Orthography and Modality Influence Speech Production in Adults and Children

Purpose
The acquisition of literacy skills influences the perception and production of spoken language. We examined if orthography influences implicit processing in speech production in child readers and in adult readers with low and high reading proficiency.
Method
Children (n = 17), adults with typical reading skills (n = 17), and adults demonstrating low reading proficiency (n = 18) repeated or read aloud nonwords varying in orthographic transparency. Analyses of implicit linguistic processing (segmental accuracy and speech movement stability) were conducted. The accuracy and articulatory stability of productions of the nonwords were assessed before and after repetition or reading.
Results
Segmental accuracy results indicate that all 3 groups demonstrated greater learning when they were able to read, rather than just hear, the nonwords. Speech movement results indicate that, for adults with poor reading skills, exposure to the nonwords in a transparent spelling reduces the articulatory variability of speech production. Reading skill was correlated with speech movement stability in the groups of adults.
Conclusions
In children and adults, orthography interacts with speech production; all participants integrate orthography into their lexical representations. Adults with poor reading skills do not use the same reading or speaking strategies as children with typical reading skills.

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Novel and De Novo Mutations Extend Association of POU3F4 with Distinct Clinical and Radiological Phenotype of Hearing Loss

by Agnieszka Pollak, Urszula Lechowicz, Anna Kędra, Piotr Stawiński, Małgorzata Rydzanicz, Mariusz Furmanek, Małgorzata Brzozowska, Maciej Mrówka, Henryk Skarżyński, Piotr H. Skarżyński, Monika Ołdak, Rafał Płoski

POU3F4 mutations (DFNX2) are the most prevalent among non-syndromic X-linked hearing loss (HL) identified to date. Clinical manifestations of DFNX2 usually comprise congenital HL either sensorineural or mixed, a tendency towards perilymphatic gusher during otologic surgery and temporal bone malformations. The aim of the present study was to screen for POU3F4 mutations in a group of 30 subjects with a suggestive clinical phenotype as well as a group (N = 1671–2018) of unselected hearing loss patients. We also planned to analyze audiological and radiological features in patients with HL caused by POU3F4 defects. The molecular techniques used to detect POU3F4 mutations included whole exome sequencing (WES), Sanger sequencing and real-time polymerase chain reaction. Hearing status was assessed with pure-tone audiometry and auditory brainstem response. Computer tomography scans were evaluated to define the pattern of structural changes in the temporal bones. Six novel (p.Gln27*, p.Glu187*, p.Leu217*, p.Gln275*, p.Gln306*, p.Val324Asp) and two known (p.Ala116fs141*, p.Leu208*) POU3F4 mutations were detected in the studied cohort. All probands with POU3F4 defects suffered from bilateral, prelingual, severe to profound HL. Morphological changes of the temporal bone in these patients presented a similar pattern, including malformations of the internal auditory canal, vestibular aqueduct, modiolus and vestibule. Despite different localization in the POU3F4 gene all mutations severely impair the protein structure affecting at least one functional POU3F4 domain, and results in similar and severe clinical manifestations. Sequencing of the entire POU3F4 gene is recommended in patients with characteristic temporal bone malformations. Results of POU3F4 mutation testing are important not only for a proper genetic counseling, but also for adequate preparation and conduction of a surgical procedure.

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Why I Wrote My Book

Learn why I wrote my book "Kiss Your Dentist Goodbye" and why this book can help you achieve ultimate oral health! …….. Read reviews from people who have already read my book!

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Novel and De Novo Mutations Extend Association of POU3F4 with Distinct Clinical and Radiological Phenotype of Hearing Loss

by Agnieszka Pollak, Urszula Lechowicz, Anna Kędra, Piotr Stawiński, Małgorzata Rydzanicz, Mariusz Furmanek, Małgorzata Brzozowska, Maciej Mrówka, Henryk Skarżyński, Piotr H. Skarżyński, Monika Ołdak, Rafał Płoski

POU3F4 mutations (DFNX2) are the most prevalent among non-syndromic X-linked hearing loss (HL) identified to date. Clinical manifestations of DFNX2 usually comprise congenital HL either sensorineural or mixed, a tendency towards perilymphatic gusher during otologic surgery and temporal bone malformations. The aim of the present study was to screen for POU3F4 mutations in a group of 30 subjects with a suggestive clinical phenotype as well as a group (N = 1671–2018) of unselected hearing loss patients. We also planned to analyze audiological and radiological features in patients with HL caused by POU3F4 defects. The molecular techniques used to detect POU3F4 mutations included whole exome sequencing (WES), Sanger sequencing and real-time polymerase chain reaction. Hearing status was assessed with pure-tone audiometry and auditory brainstem response. Computer tomography scans were evaluated to define the pattern of structural changes in the temporal bones. Six novel (p.Gln27*, p.Glu187*, p.Leu217*, p.Gln275*, p.Gln306*, p.Val324Asp) and two known (p.Ala116fs141*, p.Leu208*) POU3F4 mutations were detected in the studied cohort. All probands with POU3F4 defects suffered from bilateral, prelingual, severe to profound HL. Morphological changes of the temporal bone in these patients presented a similar pattern, including malformations of the internal auditory canal, vestibular aqueduct, modiolus and vestibule. Despite different localization in the POU3F4 gene all mutations severely impair the protein structure affecting at least one functional POU3F4 domain, and results in similar and severe clinical manifestations. Sequencing of the entire POU3F4 gene is recommended in patients with characteristic temporal bone malformations. Results of POU3F4 mutation testing are important not only for a proper genetic counseling, but also for adequate preparation and conduction of a surgical procedure.

http://ift.tt/2gxIe8x

Chronic blockade of the AT2 receptor with PD123319 impairs insulin signaling in C57BL/6 mice

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Publication date: Available online 12 December 2016
Source:Peptides
Author(s): M.C. Muñoz, V. Burghi, J.G. Miquet, I.A. Cervino, D.T. Quiroga, L. Mazziotta, F.P. Dominici
The renin-angiotensin system modulates insulin action. Angiotensin type 1 receptor exerts a deleterious effects while the angiotensin type 2 receptor (AT2R) appears to have beneficial effects providing protection against insulin resistance and type 2 diabetes. Although recent reports indicate that agonism of AT2R ameliorates diabetes and insulin resistance, the phenotype of AT2R-knockout mice seems to be controversial relating this aspect. Thus, in this study we have explored the role of AT2R in the control of insulin action. To that end, C57Bl/6 mice were administered the synthetic AT2R antagonist PD123319 for 21days (10mg/kg/day ip); vehicle treated animals were used as control. Glucose tolerance, metabolic parameters, in vivo insulin signaling in main insulin-target tissues as well as levels of adiponectin, TNF-α, MCP-1 and IL-6 in adipose tissue were assessed. AT2R blockade with PD123319 induced a marginal effect on glucose homeostasis but an important reduction in the insulin-induced phosphorylation of the insulin receptor and Akt in both liver and adipose tissue. Insulin signaling in skeletal muscle remained unaltered after treatment with PD123319, which could explain the minimal effect on glucose homeostasis induced by PD123319. Our current results reinforce the notion that the AT2R has a physiological role in the conservation of insulin action.



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Imaging of Solid Renal Masses

Publication date: Available online 12 December 2016
Source:Radiologic Clinics of North America
Author(s): Fernando U. Kay, Ivan Pedrosa

Teaser

Detection of solid renal masses has increased, although it has not resulted in significant mortality reduction from renal cell carcinoma. Efforts for improved lesion characterization have been pursued and incorporated in management algorithms, in order to distinguish clinically significant tumors from favorable or benign conditions. Concurrently, imaging methods have produced evidence supporting their role as useful tools not only in lesion detection but also characterization. In addition, newer modalities, such as contrast-enhanced ultrasonography, and advanced applications of MR imaging, are being investigated. This article reviews the current role of different imaging methods in the characterization of solid renal masses.


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Practical Approach to Adrenal Imaging

Publication date: Available online 12 December 2016
Source:Radiologic Clinics of North America
Author(s): Khaled M. Elsayes, Sally Emad-Eldin, Ajaykumar C. Morani, Corey T. Jensen

Teaser

Various pathologies can affect the adrenal gland. Noninvasive cross-sectional imaging is used for evaluating adrenal masses. Accurate diagnosis of adrenal lesions is critical, especially in cancer patients; the presence of adrenal metastasis changes prognosis and treatment. Characterization of adrenal lesions predominantly relies on morphologic and physiologic features to enable correct diagnosis and management. Key diagnostic features to differentiate benign and malignant adrenal lesions include presence/absence of intracytoplasmic lipid, fat cells, hemorrhage, calcification, or necrosis and locoregional and distant disease; enhancement pattern and washout values; and lesion size and stability. This article reviews a spectrum of adrenal pathologies.


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Benefit of SLIT and SCIT for Allergic Rhinitis and Asthma

Abstract

Allergen immunotherapy (AIT) has been in use since more than one century, when Leonard Noon experimentally proved its efficacy in hayfever (Noon, in Lancet 1:1572–3, 1911). Since then, AIT was administered only as subcutaneous injections (SCIT) until the sublingual route (SLIT) was proposed in 1986. The use of SLIT was proposed following several surveys from the USA and UK that repeatedly reported fatalities due to SCIT (Lockey et al. in J Allergy Clin Immunol 75(1): 166, 1985; Lockey et al. in J Allergy Clin Immunol 660–77, 1985; Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J, 293: 948, 1986). These reports raised serious concerns about the safety and the risk/benefit ratio of AIT. Many cases of life-threatening events with SCIT were due to avoidable human errors in administration, but a relevant fraction of them remained unexplained and unpredictable (Aaronson and Gandhi in J Allergy Clin Immunol 113: 1117–21, 2014). Subsequently, in a few years, SLIT gained credibility and was included in the official documents and guidelines (Table 1) (Bousquet et al. in J Allergy Clin Immunol 108(5 Supp):S146–S150, 2001; Canonica et al. in Allergy 64 (Supp 91):1–59, 2009) as a viable alternative to traditional SCIT. Of note, the local bronchial (aerosol) and the intranasal route of administration were attempted after the 1970s as alternatives to SCIT: the bronchial route was soon abandoned due to the poor efficacy and/or side effects, and the local nasal route, although effective and safe, was judged substantially impractical (Canonica and Passalacqua in J Allergy Clin Immunol 111: 437–48, 2003). In contrast to SCIT, SLIT was tested in very large clinical trials (need references), including hundreds of patients and with dose-ranging experimental designs, so that some products (tablets) for grass, mite, and ragweed were officially approved as commercial drugs by regulatory agencies such as the Food and Drug Administration and the European Medicines Agency and the optimal content for the maintenance dose was identified for selected allergens. In parallel, the knowledge on the mechanisms of action of AIT was rapidly refined, leading to further improvements, such as the chemically modified extracts and the use of adjuvants to enhance efficacy and safety. In addition, in the last 10 years, there has been an increasing scientific and clinical interest in AIT applied to food allergies, in particular in children, with the use of orally administered extracts (Albin and Nowak-Węgrzyn in Immunol Allergy Clin North Am 35: 77–100, 2015). The results are so far encouraging, at least for cow's milk, egg, and peanut, although the use of treatment is still restricted to clinical trials or within specialized centers. Finally, the introduction of molecular- or component-resolved diagnosis has allowed detailing the prescription of AIT, by better delineating true sensitization versus cross-reactivity (Canonica et al. in World Allergy Organ J 6(1):17, 2013). This latter point is also in strict relation to the use of recombinant, engineered or highly purified molecules, instead of raw extracts, for the desensitization process.



http://ift.tt/2hvspiy

Benefit of SLIT and SCIT for Allergic Rhinitis and Asthma

Abstract

Allergen immunotherapy (AIT) has been in use since more than one century, when Leonard Noon experimentally proved its efficacy in hayfever (Noon, in Lancet 1:1572–3, 1911). Since then, AIT was administered only as subcutaneous injections (SCIT) until the sublingual route (SLIT) was proposed in 1986. The use of SLIT was proposed following several surveys from the USA and UK that repeatedly reported fatalities due to SCIT (Lockey et al. in J Allergy Clin Immunol 75(1): 166, 1985; Lockey et al. in J Allergy Clin Immunol 660–77, 1985; Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J, 293: 948, 1986). These reports raised serious concerns about the safety and the risk/benefit ratio of AIT. Many cases of life-threatening events with SCIT were due to avoidable human errors in administration, but a relevant fraction of them remained unexplained and unpredictable (Aaronson and Gandhi in J Allergy Clin Immunol 113: 1117–21, 2014). Subsequently, in a few years, SLIT gained credibility and was included in the official documents and guidelines (Table 1) (Bousquet et al. in J Allergy Clin Immunol 108(5 Supp):S146–S150, 2001; Canonica et al. in Allergy 64 (Supp 91):1–59, 2009) as a viable alternative to traditional SCIT. Of note, the local bronchial (aerosol) and the intranasal route of administration were attempted after the 1970s as alternatives to SCIT: the bronchial route was soon abandoned due to the poor efficacy and/or side effects, and the local nasal route, although effective and safe, was judged substantially impractical (Canonica and Passalacqua in J Allergy Clin Immunol 111: 437–48, 2003). In contrast to SCIT, SLIT was tested in very large clinical trials (need references), including hundreds of patients and with dose-ranging experimental designs, so that some products (tablets) for grass, mite, and ragweed were officially approved as commercial drugs by regulatory agencies such as the Food and Drug Administration and the European Medicines Agency and the optimal content for the maintenance dose was identified for selected allergens. In parallel, the knowledge on the mechanisms of action of AIT was rapidly refined, leading to further improvements, such as the chemically modified extracts and the use of adjuvants to enhance efficacy and safety. In addition, in the last 10 years, there has been an increasing scientific and clinical interest in AIT applied to food allergies, in particular in children, with the use of orally administered extracts (Albin and Nowak-Węgrzyn in Immunol Allergy Clin North Am 35: 77–100, 2015). The results are so far encouraging, at least for cow's milk, egg, and peanut, although the use of treatment is still restricted to clinical trials or within specialized centers. Finally, the introduction of molecular- or component-resolved diagnosis has allowed detailing the prescription of AIT, by better delineating true sensitization versus cross-reactivity (Canonica et al. in World Allergy Organ J 6(1):17, 2013). This latter point is also in strict relation to the use of recombinant, engineered or highly purified molecules, instead of raw extracts, for the desensitization process.



http://ift.tt/2hvspiy

Benefit of SLIT and SCIT for Allergic Rhinitis and Asthma

Abstract

Allergen immunotherapy (AIT) has been in use since more than one century, when Leonard Noon experimentally proved its efficacy in hayfever (Noon, in Lancet 1:1572–3, 1911). Since then, AIT was administered only as subcutaneous injections (SCIT) until the sublingual route (SLIT) was proposed in 1986. The use of SLIT was proposed following several surveys from the USA and UK that repeatedly reported fatalities due to SCIT (Lockey et al. in J Allergy Clin Immunol 75(1): 166, 1985; Lockey et al. in J Allergy Clin Immunol 660–77, 1985; Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J, 293: 948, 1986). These reports raised serious concerns about the safety and the risk/benefit ratio of AIT. Many cases of life-threatening events with SCIT were due to avoidable human errors in administration, but a relevant fraction of them remained unexplained and unpredictable (Aaronson and Gandhi in J Allergy Clin Immunol 113: 1117–21, 2014). Subsequently, in a few years, SLIT gained credibility and was included in the official documents and guidelines (Table 1) (Bousquet et al. in J Allergy Clin Immunol 108(5 Supp):S146–S150, 2001; Canonica et al. in Allergy 64 (Supp 91):1–59, 2009) as a viable alternative to traditional SCIT. Of note, the local bronchial (aerosol) and the intranasal route of administration were attempted after the 1970s as alternatives to SCIT: the bronchial route was soon abandoned due to the poor efficacy and/or side effects, and the local nasal route, although effective and safe, was judged substantially impractical (Canonica and Passalacqua in J Allergy Clin Immunol 111: 437–48, 2003). In contrast to SCIT, SLIT was tested in very large clinical trials (need references), including hundreds of patients and with dose-ranging experimental designs, so that some products (tablets) for grass, mite, and ragweed were officially approved as commercial drugs by regulatory agencies such as the Food and Drug Administration and the European Medicines Agency and the optimal content for the maintenance dose was identified for selected allergens. In parallel, the knowledge on the mechanisms of action of AIT was rapidly refined, leading to further improvements, such as the chemically modified extracts and the use of adjuvants to enhance efficacy and safety. In addition, in the last 10 years, there has been an increasing scientific and clinical interest in AIT applied to food allergies, in particular in children, with the use of orally administered extracts (Albin and Nowak-Węgrzyn in Immunol Allergy Clin North Am 35: 77–100, 2015). The results are so far encouraging, at least for cow's milk, egg, and peanut, although the use of treatment is still restricted to clinical trials or within specialized centers. Finally, the introduction of molecular- or component-resolved diagnosis has allowed detailing the prescription of AIT, by better delineating true sensitization versus cross-reactivity (Canonica et al. in World Allergy Organ J 6(1):17, 2013). This latter point is also in strict relation to the use of recombinant, engineered or highly purified molecules, instead of raw extracts, for the desensitization process.



http://ift.tt/2hvspiy

Benefit of SLIT and SCIT for Allergic Rhinitis and Asthma

Abstract

Allergen immunotherapy (AIT) has been in use since more than one century, when Leonard Noon experimentally proved its efficacy in hayfever (Noon, in Lancet 1:1572–3, 1911). Since then, AIT was administered only as subcutaneous injections (SCIT) until the sublingual route (SLIT) was proposed in 1986. The use of SLIT was proposed following several surveys from the USA and UK that repeatedly reported fatalities due to SCIT (Lockey et al. in J Allergy Clin Immunol 75(1): 166, 1985; Lockey et al. in J Allergy Clin Immunol 660–77, 1985; Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J, 293: 948, 1986). These reports raised serious concerns about the safety and the risk/benefit ratio of AIT. Many cases of life-threatening events with SCIT were due to avoidable human errors in administration, but a relevant fraction of them remained unexplained and unpredictable (Aaronson and Gandhi in J Allergy Clin Immunol 113: 1117–21, 2014). Subsequently, in a few years, SLIT gained credibility and was included in the official documents and guidelines (Table 1) (Bousquet et al. in J Allergy Clin Immunol 108(5 Supp):S146–S150, 2001; Canonica et al. in Allergy 64 (Supp 91):1–59, 2009) as a viable alternative to traditional SCIT. Of note, the local bronchial (aerosol) and the intranasal route of administration were attempted after the 1970s as alternatives to SCIT: the bronchial route was soon abandoned due to the poor efficacy and/or side effects, and the local nasal route, although effective and safe, was judged substantially impractical (Canonica and Passalacqua in J Allergy Clin Immunol 111: 437–48, 2003). In contrast to SCIT, SLIT was tested in very large clinical trials (need references), including hundreds of patients and with dose-ranging experimental designs, so that some products (tablets) for grass, mite, and ragweed were officially approved as commercial drugs by regulatory agencies such as the Food and Drug Administration and the European Medicines Agency and the optimal content for the maintenance dose was identified for selected allergens. In parallel, the knowledge on the mechanisms of action of AIT was rapidly refined, leading to further improvements, such as the chemically modified extracts and the use of adjuvants to enhance efficacy and safety. In addition, in the last 10 years, there has been an increasing scientific and clinical interest in AIT applied to food allergies, in particular in children, with the use of orally administered extracts (Albin and Nowak-Węgrzyn in Immunol Allergy Clin North Am 35: 77–100, 2015). The results are so far encouraging, at least for cow's milk, egg, and peanut, although the use of treatment is still restricted to clinical trials or within specialized centers. Finally, the introduction of molecular- or component-resolved diagnosis has allowed detailing the prescription of AIT, by better delineating true sensitization versus cross-reactivity (Canonica et al. in World Allergy Organ J 6(1):17, 2013). This latter point is also in strict relation to the use of recombinant, engineered or highly purified molecules, instead of raw extracts, for the desensitization process.



http://ift.tt/2hvspiy

The Next Sleep And Wellness Conference Has Been Announced!

The American Sleep and Breathing Academy's (ASBA) Annual Sleep and Wellness Conference has been announced. Prepare to join the ASBA in Arizona's beautiful spring weather April 21-22, 2017 at the Pointe Hilton Spa and Resort – Tapatio Cliffs location for our largest event of the year. The weekend will boast an all-star speaker lineup including industry leaders Dr. Paul Serrano, Dr. Rod Willey, Dr. Paul Vanwalleghem, Dr. David Singh, Dr. Kent Smith, Dr. Kevin Mueller, Dr. Erin Elliott and Congressman Marty Russo.

What makes this event unique is it will give you the opportunity to learn the latest clinical information, news, laws, regulations and marketing strategies in dental sleep medicine. There is a bonus! Successful practices have precise systems in place that ensure every patient undergoes quality care and business models that make treating obstructive sleep apnea a profitable service. Treating sleep apnea is an honorable way to positively impact the lives of your patients, but the key word is profitable. Other organizations will exclusively show you how to treat the patient, failing to show you ways to put them in your chair. Getting patients in the chair is a shared skill among the ASBA speakers and they will show you how!

You might be thinking, "I'm from a small city; what if the speakers give me business models and marketing strategies from places like Chicago or New York City?" The ASBA has you covered. The speakers at the Sleep and Wellness Conference serve a variety of communities in different areas of the country, meaning you will take home valuable information that can be applied directly to your practice regardless of where you're coming from.

Don't waste any more time thinking about whether you're going to attend. Take advantage of the early rate while it is still available!

 

Early Registration Rates

Member Fee $395

Nonmember Fee $795

New Membership/Full Conference Fee $875

 

Conference Information

David Gergen – david@myasba.com

Alan Hickey – alan@myasba.com

 

Exhibitor Information

Skylar Faulkner – skylar@myasba.com

 

Registration and more information can be found at sleep-conference.com

 

 



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Innovative application of metal-organic frameworks for encapsulation and controlled release of allyl isothiocyanate

Publication date: 15 April 2017
Source:Food Chemistry, Volume 221
Author(s): Elham Lashkari, Hao Wang, Linshu Liu, Jing Li, Kit Yam
This research investigated the technical feasibility of metal-organic frameworks (MOFs) as novel delivery systems for encapsulation and controlled release of volatile allyl isothiocyanate (AITC) molecules. We hypothesized that water vapor molecules could act as an external stimulus to trigger the release of AITC molecules encapsulated in MOFs. To test this hypothesis, three MOFs—HKUST-1, MOF-74(Zn), and RPM6-Zn—were selected based on their structural properties and AITC molecular characteristics. Results from adsorption-desorption and GC headspace analyses showed that these MOFs could encapsulate and retain AITC molecules within their pores under low (30–35%) relative humidity (RH) conditions. In contrast, the release of AITC molecules from all these MOFs was triggered under high RH (95–100%) conditions. These findings along with results from SEM, TEM, and XRPD studies support our hypothesis that water vapors could trigger the AITC release from these MOFs, indicating that development of the AITC-MOFs delivering system is technically feasible.



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Effect of pulsed electric fields (PEF) on accumulation of selenium and zinc ions in Saccharomyces cerevisiae cells

Publication date: 15 April 2017
Source:Food Chemistry, Volume 221
Author(s): Urszula Pankiewicz, Monika Sujka, Radosław Kowalski, Artur Mazurek, Marzena Włodarczyk-Stasiak, Jerzy Jamroz
The cultures of Saccharomyces cerevisiae were treated with pulsed electric fields (PEF) in order to obtain a maximum accumulation of selenium and zinc ions (simultaneously) in the biomass.The following concentrations: 100μgSe/ml and 150μgZn/ml medium were assumed to be optimal for the maximum accumulation of these ions, that is 43.07mg/gd.m. for selenium and 14.48mg/gd.m. for zinc, in the cultures treated with PEF. At optimal PEF parameters: electric field strength of 3kV/cm and pulse width of 10μs after the treatment of 20-h culture for 10min, the maximum accumulation of both ions in the yeast cells was observed. Application of PEF caused the increase of ions accumulation by 65% for selenium and 100% for zinc. Optimization of PEF parameters led to the further rise in the both ions accumulation resulting in over 2-fold and 2.5-fold higher concentration of selenium and zinc.



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Effect of metal ions on the binding reaction of (−)-epigallocatechin gallate to β-lactoglobulin

Publication date: 15 April 2017
Source:Food Chemistry, Volume 221
Author(s): Liangliang Zhang, Indra Dev Sahu, Man Xu, Yongmei Wang, Xinyu Hu
The effects of metal ions (Cu2+, Sn2+, Zn2+, Mn2+, Al3+ and Fe3+) on the interaction between (−)-epigallocatechin-3-gallate (EGCg) and β-lactoglobulin (β-Lg) were investigated via fluorescence and circular dichroism (CD) spectroscopy. The results of the fluorescence titration experiment demonstrated that the addition of Cu2+ increases the quenching efficiency of EGCg to β-Lg by more than EGCg alone, while Mn2+, Al3+ and Zn2+ decrease the quenching efficiency of EGCg to β-Lg by less than EGCg alone. [β-Lg-Mn], [β-Lg-Al], [β-Lg-Zn] and [β-Lg-Sn] obviously decreased the apparent binding affinities (Ka) of EGCg to β-Lg by 95.53%, 81.94%, 44.66% and 38.58%, respectively, whereas [β-Lg-Cu] significantly increased the Ka of EGCg for β-Lg by 115.44%. The results of CD spectroscopy experiment showed the α-helix content of β-Lg decreased with the addition of Cu or Al, indicating that the β-Lg-Cu and β-Lg-Al interaction resulted in unfolding of the secondary structure of β-Lg.



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Assessing trace elements in striped dolphins from the Strait of Gibraltar: Clues to link the bioaccumulation in the westernmost Mediterranean Sea area and nearest Atlantic Ocean

Publication date: March 2017
Source:Chemosphere, Volume 170
Author(s): Elisa Rojo-Nieto, Carolina Fernández-Maldonado
Dolphins are considered sentinel species in the marine environment. The Strait of Gibraltar is the only passage between the Mediterranean Sea and the Atlantic Ocean, being the transitional region which connects these two basins and one of the most important routes of cetacean migration worldwide. In this work, eight trace elements (TE) were studied in 45 samples of liver, kidney and muscle, from 15 specimens stranded in this study area. The preliminary results show, among others, the patterns of distribution of the TE in the target organs studied, the influence of sex, length and developmental stage in these TE concentrations and the Se/Hg ratio. Subsequently, the results of TE concentrations in liver have being compared to previous data on S. coeruleoalba from the westernmost Mediterranean Sea and the nearest Atlantic Ocean. For some elements (e.g. for As), concentrations are similar to those obtained from Atlantic samples, despite in other cases (e.g. for Cd) results are lined up with those observed in Mediterranean studies. In addition, in the case of some TE (e.g. Se and Zn) the results are in the middle of those reported for both basins, reinforcing the idea of the Strait of Gibraltar being a transitional zone. Present study is the first research regarding this issue in this outstanding region, aiming to give insights of how this matchless area can help to link TE concentrations observed in these Atlantic and Mediterranean threatened species.



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Issue Information - TOC



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Use of skin-lightening products among selected urban communities in Accra, Ghana

Abstract

Background

The practice of skin lightening has been reported from North America, Europe, Asia, and Africa. In literature, some prevalence rates exceed 50%, and both sexes are involved. Common agents used include hydroquinone, mercury, corticosteroids, and caustic agents. The agents are easily accessible and affordable with very little regulation. Cutaneous and systemic side effects occur but do not appear to be a deterrent, as the notion of light skin as a surrogate for beauty is strong. In Ghana, anecdotal reports of high bleaching rates among certain urban communities resulted in a study supported by the Food and Drugs Authority to determine various facets of this practice.

Methods

A cross-sectional study among adults in selected urban fishing communities of Accra was undertaken. Consecutive cases were enrolled after written informed consent. A questionnaire was administered, followed by physical examination and clinical photographs. Descriptive statistics were used to analyze the data.

Results

Of the 555 participants from the three communities, prevalence was 279 (50.3%). Duration of use ranged from 2 months to 17 years. Approximately 212 (76%) used more than one product, and 231 (82%) used agents on their face and body. Dermatological features were hypopigmentation 270 (96.8%), other color changes including ochronosis 241 (86.4%), changes in consistency 141 (50.3%), striae 157 (56.3%), and infections 42 (15.1%).

Conclusions

The prevalence of skin bleaching was 50.3% in these communities, which is high considering the adverse effects from the practice. We recommend regulation of products by enforcing the law, more education, and a population prevalence study.



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A case-control study on the association of pulse oral poliomyelitis vaccination and Gianotti-Crosti syndrome

Abstract

Background

Since 1995, the Indian government has been launching two National Immunization Days (NIDs) annually to administer oral polio vaccines (OPVs) to children under the age of 5. Our aim was to investigate the association between OPVs and Gianotti-Crosti syndrome (GCS).

Methods

A board-certified dermatologist in solo practice conducted the examinations. The patients consulted without the need of a referral. We retrieved files of all children under the age of 5 who were diagnosed with GCS in 18 months. There were three NIDs during these months. We charted the number of children 1 month before, 1 week before, 1 week after, and 1 month after the three NIDs.

Results

A total of 116 children (49 boys and 67 girls) under the age of 5 with GCS were found (average age: 2.9 years) within these 18 months of three NIDs. Eleven (9.5%) and 105 (90.5%) children developed GCS 1 month before and 1 month following OPV administration, respectively (RR: 1.81; 95% CI: 1.40–2.35; P < 0.0001). Three (2.6%) and 58 (50.0%) children developed GCS 1 week before and 1 week after OPV administration, respectively (RR: 1.90; 95% CI: 1.12–3.22; P < 0.0001).

Conclusions

The administration of OPV is significantly associated with the occurrence of GCS in the part of the world that we investigated. As we demonstrated a temporal relationship, this association is likely to be causal.



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The role of local temperature and other clinical characteristics of localized scleroderma as markers of disease activity

Abstract

Background

Determining the activity of localized scleroderma (LS) remains crucial for decision making, and reliable clinical indicators of activity are lacking. Our objective in this study was to analyze the utility of infrared thermography (IRT) in assessing the activity of LS according to existing clinical scales. A secondary objective was to study whether clinical characteristics of patients and/or IRT have any role in predicting the activity of LS.

Methods

In this cross-sectional study, the activity of LS was determined using a visual analog scale (VAS), a dyspigmentation-induration-erythema-telangiectasias (DIET) scale, and a localized scleroderma skin severity index (LoSSI). Local temperature was measured by IRT.

Results

We studied 56 patients with a median age of 14.2 years. The mean difference in temperature between the affected and unaffected skin was 0.29°C. The comparison of patients with active versus inactive LS (using a 50% composite score cutoff) according to differences in temperature was not significant. An exploratory regression analysis showed an insignificant association of difference in temperature and other clinical characteristics for activity of LS. Our relatively small sample size consisted primarily of patients with low to moderate activity, and the lack of a standard definition of activity of LS was another limitation.

Conclusions

There is a possible role for temperature and other clinical characteristics as predictors of activity of LS. More studies and better definitions of activity in LS are needed.



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Cutaneous epithelioid hemangioendothelioma treated with Mohs micrographic surgery



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Periungual sporotrichosis: a diagnostic challenge



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Transoral robotic surgery (TORS) for excision of a retropharyngeal intramuscular lipoma

To describe the feasibility, effectiveness, and improved morbidity profile of transoral robotic surgery (TORS) for the excision of a retropharyngeal intramuscular lipoma.

http://ift.tt/2gxaZSF

Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders.

http://ift.tt/2gxofXA

CD14 is not involved in the uptake of synthetic CpG oligonucleotides

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Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Jessica Li, Fatma Ahmet, Meredith O'Keeffe, Mireille H. Lahoud, William R. Heath, Irina Caminschi
We have previously shown that DEC205, a surface receptor expressed at high levels on CD8+DC, is able to capture synthetic CpG oligonucleotides (ODN) and is required for optimal responsiveness. However, even in the absence of DEC205, CD8+DC are able to respond to CpG ODN, albeit suboptimally. This suggested that additional receptors might contribute to the uptake of CpG ODN. CD14 represented an ideal candidate as it is expressed by DC and has been shown to bind and facilitate the uptake of CpG ODN. However, when CD14-deficient (CD14−/−) mice and normal B6 mice were injected with CpG ODN, CD8+DC were equivalently activated as assessed by the upregulation of the co-stimulatory molecules CD40 and CD80. Furthermore, the level of serum IL-6 and IL-12 produced in response to CpG ODN was comparable in CD14−/− and B6 mice. Importantly, mice deficient in both DEC205 and CD14 had comparable responses to mice lacking DEC205 alone, both in terms of cytokine production and DC activation, arguing that CD14 did not contribute to responses to CpG ODN. For CD14 to act as an uptake receptor for CpG ODN, it must first capture CpG ODN. To this end we assessed the capacity of cell surface CD14 to bind CpG ODN. Although we unequivocally confirmed that CD14 is required for the binding of its known ligand LPS, CD14 was not required for binding or responses to A-, B-, and C- Class CpG ODN. Our studies dispute the claim that CD14 is involved in CpG ODN capture.



http://ift.tt/2gxpqpN

CD14 is not involved in the uptake of synthetic CpG oligonucleotides

alertIcon.gif

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Jessica Li, Fatma Ahmet, Meredith O'Keeffe, Mireille H. Lahoud, William R. Heath, Irina Caminschi
We have previously shown that DEC205, a surface receptor expressed at high levels on CD8+DC, is able to capture synthetic CpG oligonucleotides (ODN) and is required for optimal responsiveness. However, even in the absence of DEC205, CD8+DC are able to respond to CpG ODN, albeit suboptimally. This suggested that additional receptors might contribute to the uptake of CpG ODN. CD14 represented an ideal candidate as it is expressed by DC and has been shown to bind and facilitate the uptake of CpG ODN. However, when CD14-deficient (CD14−/−) mice and normal B6 mice were injected with CpG ODN, CD8+DC were equivalently activated as assessed by the upregulation of the co-stimulatory molecules CD40 and CD80. Furthermore, the level of serum IL-6 and IL-12 produced in response to CpG ODN was comparable in CD14−/− and B6 mice. Importantly, mice deficient in both DEC205 and CD14 had comparable responses to mice lacking DEC205 alone, both in terms of cytokine production and DC activation, arguing that CD14 did not contribute to responses to CpG ODN. For CD14 to act as an uptake receptor for CpG ODN, it must first capture CpG ODN. To this end we assessed the capacity of cell surface CD14 to bind CpG ODN. Although we unequivocally confirmed that CD14 is required for the binding of its known ligand LPS, CD14 was not required for binding or responses to A-, B-, and C- Class CpG ODN. Our studies dispute the claim that CD14 is involved in CpG ODN capture.



http://ift.tt/2gxpqpN

Transoral robotic surgery (TORS) for excision of a retropharyngeal intramuscular lipoma

To describe the feasibility, effectiveness, and improved morbidity profile of transoral robotic surgery (TORS) for the excision of a retropharyngeal intramuscular lipoma.

http://ift.tt/2gxaZSF

Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders.

http://ift.tt/2gxofXA

Aqueous fraction of Alstonia boonei de Wild leaves suppressed inflammatory responses in carrageenan and formaldehyde induced arthritic rats

Publication date: February 2017
Source:Biomedicine & Pharmacotherapy, Volume 86
Author(s): Omowumi O. Akinnawo, God'swill N. Anyasor, Odutola Osilesi
Alstonia boonie de Wild is an ethnomedical plant used as therapy against inflammatory disorders. This study evaluated the most active anti-inflammatory and anti-oxidant fraction of A. boonei leaves using in vitro and in vivo models. Quantitative phytochemical analysis, anti-protein denaturation and hypotonicity-induced hemolysis of human red blood cell membrane (HRBC), radical scavenging activity assays, carrageenan and formaldehyde-induced inflammation models were carried out. Results showed that aqueous and ethyl acetate fractions of 70% methanol extract of A. boonie leaves contained high quantities of total phenolic and flavonoid compounds compared with hexane and butanol fractions. Aqueous fraction of A. boonie leaves significantly (P<0.05) inhibited heat-induced protein denaturation, stabilized hypotonicity-induced hemolysis of HRBC, scavenged DPPH, NO and H2O2 radicals in a concentration-dependent manner compared with other fractions in vitro. In addition, orally administered 50–250–mg/kg body weight (b.w.) aqueous fraction of A. boonei leaves suppressed carrageenan-induced rat paw edema thickness by 74.32%, 79.22% and 89.86% respectively at 6th h in a dose-dependent manner comparable with animals treated with standard diclofenac sodium (88.69%) in vivo. Furthermore, investigation of formaldehyde-induced inflammation in rats showed that 50–250 mg/kg b.w. aqueous fraction of A. boonei reduced plasma alanine aminotransferase and aspartate aminotransferase activities. Aqueous fraction of A. boonei also suppressed eosinophils, monocytes and basophils, total white blood cell, total platelet, neutrophil and lymphocyte counts and modulated plasma lipid profile compared with control group. Aqueous fraction of A. boonei leaves exhibited substantial active anti-inflammatory and antioxidant activities. Hence, an aqueous fraction of A. boonei leaves could be channeled towards pharmaceutical drug development. In addition, this study provided scientific insight to account for the traditional use of A. boonei leaves in ethnomedical practice.

Graphical abstract

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Does Peer Review of Radiation Plans Affect Clinical Care? A Systematic Review of the Literature

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Brunskill, Kelsey, BMRSc; Nguyen, Timothy K., MD; Boldt, R. Gabriel, MSEd, MLIS;...
Summary Although physician peer review of radiation treatment plans is recommended by some organizations as a quality assurance process, its impact on clinical care is not well-defined. Through a systematic review of the published data, we found t...

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In Regard to Perrier et al

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Escande, Alexandre, MD; Van Gestel, Dirk, MD, PhD; Lacornerie, Thomas, MSc;...
To the Editor: We thank Perrier et al for presenting a cost analysis evaluation of 2 irradiation techniques used in France in their article, "Cost analysis of complex radiation therapy for patients with head and neck cancer" (1) . Nevertheless, se...

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In Regard to Ramroth et al

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Fiorica, Francesco, MD, PhD
To the Editor: Ramroth et al (1) recently published a very interesting meta-analysis investigating whether higher doses of radiation therapy for lung cancer result in longer survival. Analyzing pooled data from 25 randomized clinical trials, the a...

http://ift.tt/2hEODus

Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Polishchuk, Alexei L., MD, PhD; Mishra, Kavita K., MD, MPH; Weinberg, Vivian, PhD;...
Summary Proton beam radiation therapy (PBRTacrnm1) of uveal melanoma (UMacrnm1) provides effective local control with the potential for vision preservation. In this study, long-term functional follow-up of a large, uniformly treated and assessed *...

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Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Schüler, Emil, PhD; Trovati, Stefania, PhD; King, Gregory, PhD;...
Summary A key factor limiting the effectiveness of radiation therapy is normal tissue toxicity, and recent preclinical data have shown that ultra-high dose rate irradiation (>50 Gy/s, "FLASH") potentially mitigates this effect. However, researc...

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Erratum to Guo W, Du S, Yang L, et al. Stat3 activation mediates stem cell, DNA repair, and immunosuppressive properties in crizotinib-resistance EML4-ALK-rearranged lung cancer. Int J Radiat Oncol Biol Phys 2016;96:S76-S77

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1
Abstracts from the 2016 ASTRO Annual Meeting that need correction: Abstract #172 The abstract title and author line were incorrectly listed. Below is the correct version: Stat3 Activation Mediates Stem Cell, DNA Repair, and Immunosuppressive Prope...

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In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Maeda, Azusa, PhD; Chen, Yonghong, MSc, MD; Bu, Jiachuan, MSc;...
Summary In vivo imaging methods were used to investigate the effects of high-dose irradiation on tumor vasculature and microenvironment using a BxPC3 pancreatic tumor model. A single dose of 24 Gy caused transient vascular dysfunction associated w...

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Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Mumbrekar, Kamalesh Dattaram, PhD; Bola Sadashiva, Satish Rao, PhD; Kabekkodu, Shama Prasada, PhD;...
Summary Radiation therapy-induced normal tissue toxicity limits therapeutic outcomes. The present study evaluated the possible associations between genetic variants in previously described radioresponsive genes and the risk of developing acute ski...

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Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Chapman, Bhavana V., MD; Gill, Beant S., MD; Viswanathan, Akila N., MD, MPH;...
Summary A positive surgical margin after radical vulvectomy for vulvar squamous cell carcinoma increases the frequency of local recurrence, which may be difficult to salvage. Although adjuvant radiation therapy has been shown to improve local cont...

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Introducing: The Red Journal Gray Zone

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Palma, David A., MD, PhD; Yom, Sue S., MD, PhD, MAS; Bennett, Katherine Egan;...
The ultimate goal of radiation oncology research is to improve clinical care. As a specialty, we tackle diverse research questions, addressing every type of cancer and encompassing cancer biology and radiation physics. But despite our best efforts...

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Meetings

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1
January 19-21, 2017 2017 Gastrointestinal Cancers Symposium San Francisco www.gicasym.org February 16-18, 2017 2017 Genitourinary Cancers Symposium Orlando, Fla www.gucasym.org February 28-March 3, 2017 Accelerator Technology Education Course Toro...

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Try to Avoid Tri-Modality Treatment

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Sadraei, Nooshin Hashemi, MD; Huth, Bradley J., MD
We prefer to avoid a tri-modality treatment for this case (1) if possible. Definitive concurrent chemo-radiation is an accepted standard of care based on multiple randomized studies and meta-analysis showing improved loco-regional control (LRCacrn...

http://ift.tt/2hvL6mq

Benchmark Credentialing Results for NRG-BR001: The First National Cancer Institute-Sponsored Trial of Stereotactic Body Radiation Therapy for Multiple Metastases

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Al-Hallaq, Hania A., PhD; Chmura, Steven J., MD, PhD; Salama, Joseph K., MD;...
Summary The present study summarizes the benchmark credentialing results for the NRG-BR001 trial. Although most plans used volumetric arc therapy and a single isocenter to target 2 nearby metastases, wide variability was found in the conformity me...

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Positron Emission Tomography/Computed Tomography Assessment After Immunochemotherapy and Irradiation Using the Lugano Classification Criteria in the IELSG-26 Study of Primary Mediastinal B-Cell Lymphoma

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Ceriani, Luca, MD; Martelli, Maurizio, MD; Gospodarowicz, Maria K., MD;...
Summary We report the analysis of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CTacrnm1) scans in 88 patients with primary mediastinal lymphoma (PMBCLacrnm1) treated using immunochemotherapy and radiation therapy in...

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Secondary Breast Cancer Risk by Radiation Volume in Women With Hodgkin Lymphoma

International Journal of Radiation Oncology, Biology, Physics, Volume 97, Issue 1, 2017 Jan 1 | Conway, Jessica L., MD; Connors, Joseph M., MD; Tyldesley, Scott, MD;...
Summary There are sparse data as to whether the risk of secondary breast cancer (SBCacrnm1) has been reduced with smaller, more modern radiation therapy (RTacrnm1) volumes in comparison with mantle radiation therapy. Using the * British Columbia C...

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Aerosol delivery of stabilized polyester-siRNA nanoparticles to silence gene expression in orthotopic lung tumors

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Publication date: February 2017
Source:Biomaterials, Volume 118
Author(s): Yunfeng Yan, Kejin Zhou, Hu Xiong, Jason B. Miller, Edward A. Motea, David A. Boothman, Li Liu, Daniel J. Siegwart
Tremendous progress has been made in the development of delivery carriers for small RNA therapeutics. However, most achievements have focused on the treatment of liver-associated diseases because conventional lipid and lipidoid nanoparticles (LNPs) readily accumulate in the liver after intravenous (i.v.) administration. Delivering RNAs to other organs and tumor tissues remains an ongoing challenge. Here, we utilized a 540-member combinatorial functional polyester library to discover nanoparticles (NPs) that enable efficacious siRNA delivery to A549 lung cancer cells in vitro and in vivo. PE4K-A13–0.33C6 and PE4K-A13–0.33C10 NPs were efficiently internalized into A549-Luc cells within 4 h. The addition of PEG 2000 DMG lipid or Pluronic F-127 onto the surface of the polyplexes reduced the surface charge of NPs, resulting in an increase of serum stability. We then explored aerosol delivery of stabilized PE4K-A13–0.33C6 and PE4K-A13–0.33C10 NPs to implanted orthotopic lung tumors. We found that by altering the administration route from i.v. to aerosol, the NPs could avoid liver accumulation and instead be specifically localized only in the lungs. This resulted in significant gene silencing in the A549 orthotopic lung tumors. Due to the ability to deliver siRNA to non-liver targets, this approach provides a privileged route for gene silencing in the lungs.



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Optimization of in vitro release of an anticonvulsant using nanocapsule-based thermogels

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Akbar Esmaeili, Sonia Singh
Controlling the release rate of anticonvulsant drugs can have a significant effect on the efficacy of these drugs and the safety with which they can be administered to patients. This study investigated in vitro release of the anticonvulsant ethosuximide from nanocapsule-based N,O-carboxymethyl chitosan and hyaluronan-methylcellulose hydrogels using two experimental designs: a one-factor-at-a-time method and an optimization method employing a Taguchi design. Using the first method, the release rate of the drug was significantly reduced compared with other delivery systems. With the second method, when the drug was blended into a hyaluronan-methylcellulose hydrogel the release rate was similarly reduced, with full release occurring after three days. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to study the drug encapsulation, and two mathematical models for evaluating encapsulation efficiency were developed. The results of this study show promise for use of nanoencapsulated thermoresponsive hydrogels in clinical delivery of anticonvulsants.

Graphical abstract

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Awake and paralyzed: The frightening final minutes for an injured teen

By Bradley Dean

When Drew Hughes self-extubated himself during a hospital-to-hospital transfer in June 2013, the subsequent attempt for rapid sequence induction (RSI) proved to be fatal. While emerging from sedation and paralysis, Drew was struggling to breathe, was unfamiliar with the environment and became combative. The nurse, paramedic and respiratory therapist caring for Drew believed that reintubation was necessary and began the process.

When caring for a patient, often the first task of any health care provider, is to secure the airway. In many circumstances, health care providers use RSI to accomplish this task. The procedure of RSI has become increasingly popular in the EMS setting, but there is a great deal of controversy about the procedure's safety and efficacy. This article is not intended to advocate for, or against the procedure, but look at the procedure and appropriate sedation and paralyzation of patients during and after, performing RSI.

The "Manual of Emergency Airway Management" defines RSI as the virtually simultaneous administration, after preoxygenation, of a potent sedative agent and a rapidly acting neuromuscular blocking agent (paralytic) to facilitate rapid tracheal intubation without interposed mechanical ventilation [1]. The combination of these medications pushed in rapid sequence following adequate oxygenation is intended to create optimal intubating conditions. Selection of the appropriate sedative agent and dose most appropriate for the clinical scenario is an important component of RSI.

Appropriate sedation for intubation
When reintubating Drew, the paramedic quickly pushed a paralytic rendering him unable to move, but no sedative or induction agent was utilized. Drew was awake and paralyzed during repeated intubation attempts. Induction agents, also known as sedatives, are integral to the performance of RSI. They provide amnestic effect, blunt sympathetic responses and can improve intubating conditions for the increased probability of success on the first attempt. The anesthetic agent rapidly renders the patient unable to appreciate, respond or recall any noxious stimuli. 

Unfortunately, research shows that Drew's experience is not an isolated case of paralysis without sedation. In a study of over a million patients, only 46.4 percent received sedatives and/or opiates before intubation [2]. Another study demonstrates that patients who are successfully intubated receive inadequate analgesia following the procedure to keep them from becoming agitated or causing self-extubation [3].

While RSI has become the cornerstone of emergency airway management for intubations that are not anticipated to be difficult, the assessment and selection of sedatives and paralytics is important. The appropriate selection and administration of medications renders the patient rapidly unconscious and flaccid in order to facilitate emergent endotracheal intubation and minimizes the risk of aspiration. Many studies debate the efficacy and outcomes of patients that undergo the procedure performed in the prehospital or inter-facility transfer setting. 

In the case of Drew, where a paralytic agent was used for intubation without sedation, he may have been fully aware of his environment, including pain, but unable to respond. In addition to this inhumane care, this circumstance allows for potentially adverse physiologic responses to airway manipulation, including tachycardia, hypertension and elevated intracranial pressure. The use of a sedative prevents or minimizes these physiologic effects and the patient is unaware of the procedure.

In some cases, providers can select an induction agent that both facilitates RSI and ameliorates the patient's underlying condition. For example, ketamine may be used as a dissociative sedative that allows the airway reflexes to remain intact and, in severe asthma patients, reduces bronchospasms. This type of induction agent may allow for the potentially difficult intubation patient to continue breathing and oxygenating without utilization of a paralytic agent potentially complicating the airway management should intubation become difficult or impossible.

Ethical aspect of paralysis during RSI
Paralysis and intubation is an extremely frightening experience for patients, so they must receive appropriate medication for sedation first. If not, they will be aware of everything happening around them while being unable to move or breathe. This procedure is deadly in the hands of the wrong provider, yet lifesaving in the hands of the proficient and skilled provider.

Paralysis with a neuromuscular blockade is a drastic measure with physical, psychological and social dangers. Many health care providers do not examine the ethical aspect of neuromuscular paralysis. When a patient is paralyzed, they lose their respiratory drive while being fully aware of their surroundings. In Drew's case, the endotracheal tube was place in his esophagus and he was not able to breathe on his own. To be fully conscious, hypoxic and paralyzed captures a modern vision of torture and helplessness.

In the event that a patient is rapidly crashing and an airway needs to be secured, it may be temporarily acceptable to push a paralytic, intubate and then immediately follow up with an amnestic agent. This should only be done in extreme cases where the establishment of an airway cannot be done and optimal paralysis is necessary. These patients are generally those who you cannot oxygenate or ventilate, which is the worst possible scenario when managing a patient's airway. 

Once a patient is intubated, the challenge is post-intubation management to prevent a number of issues, including patient self-extubation. Maintaining appropriate sedation and paralysis is a delicate balance and recognition of clinical indicators. These clinical indicators may be as simple as recognizing the slowly increasing heart rate, over breathing the ventilated rate, or recognition of the appearance of an alveolar cleft on the waveform capnography for the patient attempting to spontaneously breathe. 

While Drew's case is a tragic one, we can closely examine this case to learn important points about airway management. The process of appropriate sedation and paralysis for the initial process is just as important as the post-intubation management process. The procedure and skill of RSI can be lifesaving when appropriately applied or deadly in the hands of those who fail to recognize the importance of training and proficiency in application.

References
1. Walls RM, et.al: Manual of Emergency Airway Management. 2nd Edition. Edited by Walls RM, Murphy MF. Philadelphia: Lippincott Williams and Wilkins; 2004:22

2. Weingart GS et al. Estimates of sedation in patients undergoing intubation in US EDs. 2013. Am J of EM.

3. Jordan B et al. Inadequate provision of postintubation anxiolysis and analgesia in the ED. 2008. Am J of EM



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Awake and paralyzed: The frightening final minutes for an injured teen

By Bradley Dean

When Drew Hughes self-extubated himself during a hospital-to-hospital transfer in June 2013, the subsequent attempt for rapid sequence induction (RSI) proved to be fatal. While emerging from sedation and paralysis, Drew was struggling to breathe, was unfamiliar with the environment and became combative. The nurse, paramedic and respiratory therapist caring for Drew believed that reintubation was necessary and began the process.

When caring for a patient, often the first task of any health care provider, is to secure the airway. In many circumstances, health care providers use RSI to accomplish this task. The procedure of RSI has become increasingly popular in the EMS setting, but there is a great deal of controversy about the procedure's safety and efficacy. This article is not intended to advocate for, or against the procedure, but look at the procedure and appropriate sedation and paralyzation of patients during and after, performing RSI.

The "Manual of Emergency Airway Management" defines RSI as the virtually simultaneous administration, after preoxygenation, of a potent sedative agent and a rapidly acting neuromuscular blocking agent (paralytic) to facilitate rapid tracheal intubation without interposed mechanical ventilation [1]. The combination of these medications pushed in rapid sequence following adequate oxygenation is intended to create optimal intubating conditions. Selection of the appropriate sedative agent and dose most appropriate for the clinical scenario is an important component of RSI.

Appropriate sedation for intubation
When reintubating Drew, the paramedic quickly pushed a paralytic rendering him unable to move, but no sedative or induction agent was utilized. Drew was awake and paralyzed during repeated intubation attempts. Induction agents, also known as sedatives, are integral to the performance of RSI. They provide amnestic effect, blunt sympathetic responses and can improve intubating conditions for the increased probability of success on the first attempt. The anesthetic agent rapidly renders the patient unable to appreciate, respond or recall any noxious stimuli. 

Unfortunately, research shows that Drew's experience is not an isolated case of paralysis without sedation. In a study of over a million patients, only 46.4 percent received sedatives and/or opiates before intubation [2]. Another study demonstrates that patients who are successfully intubated receive inadequate analgesia following the procedure to keep them from becoming agitated or causing self-extubation [3].

While RSI has become the cornerstone of emergency airway management for intubations that are not anticipated to be difficult, the assessment and selection of sedatives and paralytics is important. The appropriate selection and administration of medications renders the patient rapidly unconscious and flaccid in order to facilitate emergent endotracheal intubation and minimizes the risk of aspiration. Many studies debate the efficacy and outcomes of patients that undergo the procedure performed in the prehospital or inter-facility transfer setting. 

In the case of Drew, where a paralytic agent was used for intubation without sedation, he may have been fully aware of his environment, including pain, but unable to respond. In addition to this inhumane care, this circumstance allows for potentially adverse physiologic responses to airway manipulation, including tachycardia, hypertension and elevated intracranial pressure. The use of a sedative prevents or minimizes these physiologic effects and the patient is unaware of the procedure.

In some cases, providers can select an induction agent that both facilitates RSI and ameliorates the patient's underlying condition. For example, ketamine may be used as a dissociative sedative that allows the airway reflexes to remain intact and, in severe asthma patients, reduces bronchospasms. This type of induction agent may allow for the potentially difficult intubation patient to continue breathing and oxygenating without utilization of a paralytic agent potentially complicating the airway management should intubation become difficult or impossible.

Ethical aspect of paralysis during RSI
Paralysis and intubation is an extremely frightening experience for patients, so they must receive appropriate medication for sedation first. If not, they will be aware of everything happening around them while being unable to move or breathe. This procedure is deadly in the hands of the wrong provider, yet lifesaving in the hands of the proficient and skilled provider.

Paralysis with a neuromuscular blockade is a drastic measure with physical, psychological and social dangers. Many health care providers do not examine the ethical aspect of neuromuscular paralysis. When a patient is paralyzed, they lose their respiratory drive while being fully aware of their surroundings. In Drew's case, the endotracheal tube was place in his esophagus and he was not able to breathe on his own. To be fully conscious, hypoxic and paralyzed captures a modern vision of torture and helplessness.

In the event that a patient is rapidly crashing and an airway needs to be secured, it may be temporarily acceptable to push a paralytic, intubate and then immediately follow up with an amnestic agent. This should only be done in extreme cases where the establishment of an airway cannot be done and optimal paralysis is necessary. These patients are generally those who you cannot oxygenate or ventilate, which is the worst possible scenario when managing a patient's airway. 

Once a patient is intubated, the challenge is post-intubation management to prevent a number of issues, including patient self-extubation. Maintaining appropriate sedation and paralysis is a delicate balance and recognition of clinical indicators. These clinical indicators may be as simple as recognizing the slowly increasing heart rate, over breathing the ventilated rate, or recognition of the appearance of an alveolar cleft on the waveform capnography for the patient attempting to spontaneously breathe. 

While Drew's case is a tragic one, we can closely examine this case to learn important points about airway management. The process of appropriate sedation and paralysis for the initial process is just as important as the post-intubation management process. The procedure and skill of RSI can be lifesaving when appropriately applied or deadly in the hands of those who fail to recognize the importance of training and proficiency in application.

References
1. Walls RM, et.al: Manual of Emergency Airway Management. 2nd Edition. Edited by Walls RM, Murphy MF. Philadelphia: Lippincott Williams and Wilkins; 2004:22

2. Weingart GS et al. Estimates of sedation in patients undergoing intubation in US EDs. 2013. Am J of EM.

3. Jordan B et al. Inadequate provision of postintubation anxiolysis and analgesia in the ED. 2008. Am J of EM



http://ift.tt/2hlDqQ7

The influence of genetic predisposition and autoimmune hepatitis inducing antigens in disease development

Publication date: Available online 11 December 2016
Source:Journal of Autoimmunity
Author(s): Matthias Hardtke-Wolenski, Janine Dywicki, Katja Fischer, Martin Hapke, Maren Sievers, Jerome Schlue, Mark S. Anderson, Richard Taubert, Fatih Noyan, Michael P. Manns, Elmar Jäckel
Autoimmune hepatitis (AIH) is defined as a chronic liver inflammation with loss of tolerance against hepatocytes. The etiology and pathophysiology of AIH are still poorly understood because reliable animal models are limited. Therefore, we recently introduced a model of experimental murine AIH by a self-limited adenoviral infection with the AIH type 2 antigen formiminotransferase cyclodeaminase (FTCD).We could demonstrate that break of humoral tolerance towards liver specific autoantigens like FTCD and cytochrome P450 2D6 (CYP2D6) is not dependent on the genetic background. However, the development of AIH in autoantibody positive animals is determined by genetic background genes. We could also show that the break of humoral tolerance is necessary but not sufficient for the development of AIH. In contrast the break of tolerance against the ubiquitously expressed nuclear antigens (ANAs) is strictly dependent on genetic predisposition. Priming with the UGA suppressor tRNA-associated protein (soluble liver antigen; SLA) is a strong inducer of ANA reactivity, but not sufficient to cause AIH development thereby questioning the importance of anti-SLA immune response as an important driver in AIH. Monogenetic mutations such as Aire-deficiency can cause AIH in otherwise genetically resistant strains.ConclusionThe results have important implications for our understanding of the pathophysiology of AIH development and for the interpretation of humoral antibody responses in AIH.



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Soft tissue changes in the orofacial region after rapid maxillary expansion

Abstract

Objective

Rapid maxillary expansion (RME) is usually used for expanding the maxillary bony segments. Many studies have assessed the dental and skeletal effects of the expansion treatment but few studies evaluated soft tissue changes using cone beam computed tomography (CBCT) images. This study aims to compare soft tissue changes after RME in prepubertal and postpubertal subjects using CBCT images. The null hypothesis of this study is there is no difference between prepubertal and postpubertal patients in soft tissue changes after RME treatment.

Materials and methods

A total of 28 patients (10 males, 18 females) with a bonded type of rapid maxillary expander were included in this study. The patients were divided into two subgroups according to cervical vertebral maturation stage. Prepubertal and postpubertal groups were obtained. Following the selection of CBCT images from the archive, pretreatment (T0) and postretention measurements (T1) were performed. Nine linear and one angular measurement for a total of 10 measurements were evaluated on each CBCT image. The mean differences between T0 and T1 measurements were compared by using the paired-samples t test and significance was set at P < 0.05.

Results

The largest median increase was found in cheek projection of the prepubertal group. Changes in soft tissue nasal base, philtrum width, upper lip length, columella width, columella height, and cheek projection were statistically significant (P < 0.001) in both groups. No significant differences were observed in soft tissue alar base, nostril width, nostril height, and nasolabial angle.

Conclusion

Some significant changes in facial soft tissues were observed after RME treatment but there were no significant differences between prepubertal and postpubertal subjects. The null hypothesis is accepted because there were no significant differences between the groups.



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Optimal design and patient selection for interventional trials using radiogenomic biomarkers: A REQUITE and Radiogenomics consortium statement

S01678140.gif

Publication date: Available online 12 December 2016
Source:Radiotherapy and Oncology
Author(s): Dirk De Ruysscher, Gilles Defraene, Bram L.T. Ramaekers, Philippe Lambin, Erik Briers, Hilary Stobart, Tim Ward, Søren M Bentzen, Tjeerd Van Staa, David Azria, Barry Rosenstein, Sarah Kerns, Catharine West
The optimal design and patient selection for interventional trials in radiogenomics seem trivial at first sight. However, radiogenomics do not give binary information like in e.g. targetable mutation biomarkers. Here, the risk to develop severe side effects is continuous, with increasing incidences of side effects with higher doses and/or volumes. In addition, a multi-SNP assay will produce a predicted probability of developing side effects and will require one or more cut-off thresholds for classifying risk into discrete categories. A classical biomarker trial design is therefore not optimal, whereas a risk factor stratification approach is more appropriate. Patient selection is crucial and this should be based on the dose–response relations for a specific endpoint. Alternatives to standard treatment should be available and this should take into account the preferences of patients. This will be discussed in detail.



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Gestational di-n-butyl phthalate exposure induced developmental and teratogenic anomalies in rats: a multigenerational assessment

Abstract

With the limited but ongoing usage of di-n-butyl phthalate (DBP) as plasticizer, the health effects of both phthalate and its alternatives are far from being understood. Multigenerational effects of phthalates were evaluated in rats upon exposure to DBP, aiming to provide some evidences about its potential in causing developmental teratogenicity. Gestational rats were exposed to DBP (500 mg/kg bw/day) and control groups with olive oil. On the 18th day of gestation, fetuses (F1) isolated from a few dams were subjected to prenatal screening, and the other rats were allowed to litter, and later postnatal screening was made. DBP-toxicated (F1) rats were crossed and reared up to three generations (F2 and F3) by adopting the same experimental design. A considerable decrease in the weight of placenta, low number of corpora lutea and increased resorptions, and pre- and postimplantation loss were observed in F1, F2, and F3 generations. Further, there was a decrease in the number of live births and fetal body weight with high mortality, the developmental indices showed reduction in litter size and sex ratio, and a considerable incidence of skeletal and malformation complex involving face and eye was observed in later generations compared to the first. The pre-weaning indices in neonates showed a considerable delay in physical growth milestones and poor scores in sensory motor development. Alterations noticed in the levels of thyroid profile and testosterone found to have a role in sensory motor, craniofacial development, and eye formation. In brief, results confirm multigenerational and fetotoxic effects of DBP; thereby, findings imply that developing tissues are the targets and endocrine disruption appears to be the underlying mechanism of phthalate action.



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Securitization product design for China’s environmental pollution liability insurance

Abstract

The environmental catastrophic accidents in China over the last three decades have triggered implementation of myriad policies by the government to help abate environmental pollution in the country. Consequently, research into environmental pollution liability insurance and how that can stimulate economic growth and the development of financial market in China is worthwhile. This study attempts to design a financial derivative for China's environmental pollution liability insurance to offer strong financial support for significant compensation towards potential catastrophic environmental loss exposures, especially losses from the chemical industry. Assuming the risk-free interest rate is 4%, the market portfolio expected return is 12%; the financial asset beta coefficient is 0.5, by using the capital asset pricing model (CAPM) and cash flow analysis; the principal risk bond yields 9.4%, single-period and two-period prices are 103.85 and 111.58, respectively; the principal partial-risk bond yields 10.09%, single-period and two-period prices are 103.85 and 111.58, respectively; and the principal risk-free bond yields 8.94%, single-period and two-period prices are 107.99 and 115.83, respectively. This loss exposure transfer framework transfers the catastrophic risks of environmental pollution from the traditional insurance and reinsurance markets to the capital market. This strengthens the underwriting capacity of environmental pollution liability insurance companies, mitigates the compensation risks of insurers and reinsurers, and provides a new channel to transfer the risks of environmental pollution.



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Biochar characteristics produced from rice husks and their sorption properties for the acetanilide herbicide metolachlor

Abstract

Rice husk biochar (RHBC) was prepared for use as adsorbents for the herbicide metolachlor. The characteristics and sorption properties of metolachlor adsorbed by the RHBC prepared at different pyrolysis temperatures were determined by analysis of physico-chemical characteristics, Fourier transform infrared spectroscopy (FTIR), Boehm titration, scanning electron microscopy (SEM), and thermodynamics and kinetics adsorption. With increasing pyrolysis temperature, the RHBC surface area greatly increased (from 2.57 to 53.08 m2 g−1). RHBC produced at the highest temperature (750 °C) had the greatest surface area; SEM also showed the formation of a porous surface on RH-750 biochar. The sorption capacity of RHBC also increased significantly with increasing pyrolysis temperature and was characterized by the Freundlich constant K f for the adsorption capacity increasing from 125.17–269.46 (pyrolysis at 300 °C) to 339.94–765.24 (pyrolysis at 750 °C). The results indicated that the surface area and pore diameter of RHBC produced with high pyrolysis temperature (i.e., 750 °C) had the greatest impact on the adsorption of metolachlor. The FTIR, Boehm titration, and SEM analysis showed that the greatest number of surface groups were on RHBC produced at the lowest temperature (300 °C). The biochars produced at different pyrolysis temperatures had different mechanisms of adsorbing metolachlor, which exhibited a transition from hydrogen bonds dominant at low pyrolytic temperature to pore-filling dominant at higher pyrolytic temperature.



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Decompression of a Large Periapical Lesion: A Case Report of 4-Year Follow-Up

This case report described the endodontic treatment and decompression of an extensive lesion in the anterior region of the mandible, detected during clinical and radiographic examination, in a patient with a complaint of slight tenderness to palpation in the area of mandibular right lateral incisor and canine. These teeth had been accessed without proper clinical evaluation, and their pulp tissues were exposed. The periodontal tissues were healthy, with no signs of inflammation or fistula. On radiographic examination, a radiolucent lesion with well-defined borders was seen extending from the distal root of mandibular left second premolar to the mesial root of mandibular right second premolar. Central and lateral mandibular left incisors were unresponsive to thermal pulp testing and exhibited coronal discoloration, consistent with a diagnosis of pulp necrosis. Due to persistent discharge from the root canal system during endodontic procedures despite application of intracanal medicament (calcium hydroxide paste), the decision was made to biopsy and decompress the lesion and conclude endodontic treatment. Histopathologic examination revealed a periapical granuloma. After endodontic treatment of the involved teeth, at 4-year clinical and radiographic follow-up, the affected region was almost completely repaired.

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Classical Complement Pathway Activation in the Nasal Tissue of Patients With Chronic Rhinosinusitis

S00916749.gif

Publication date: Available online 12 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Griet A. Van Roey, Christopher C. Vanison, Jeffanie Wu, Julia H. Huang, Lydia A. Suh, Roderick G. Carter, James E. Norton, Stephanie Shintani-Smith, David B. Conley, Kevin C. Welch, Anju T. Peters, Leslie C. Grammer, Kathleen E. Harris, Kathryn E. Hulse, Atsushi Kato, Whitney W. Stevens, Robert C. Kern, Robert P. Schleimer, Bruce K. Tan
BackgroundComplement plays a major role in inflammatory diseases but its involvement and mechanisms of activation in chronic rhinosinusitis (CRS) are not known.ObjectivesFollowing earlier studies discovering autoantibodies in CRS, we sought to investigate the nature, extent, and location of complement activation in nasal tissue of patients with CRS. Specifically, we were interested in whether antibody-mediated activation via the classical pathway was a major mechanism for complement activation in CRS.MethodsNasal tissue was obtained from patients with CRS and control patients. Tissue homogenates were analyzed for complement activation products (ELISA-C5b-9, C4d, activated C1 and C5a) and major complement fixing antibodies (Luminex). Tissue sections were stained for C5b-9, C4d, and laminin. Antibodies were purified using protein A/G columns from nasal polyps (NP), matching patient serum and control serum, and assayed for basement membrane binding via ELISA.ResultsC5b-9 was significantly increased in NP tissue compared to UT (uncinate tissue) of CRS with NP (CRSwNP) and CRS without NP (CRSsNP) (p<0.01). Similarly, C4d was increased in NP compared to UT of CRSwNP, CRSsNP and control (p<0.05). Activated C1 was also increased in NP tissue compared to UT of CRSsNP and control (p<0.05) and was correlated with C5a (p<0.01), local immunoglobulins, especially IgM (p<0.0001) and anti-dsDNA IgG (p<0.05). Immunofluorescence showed that C5b-9 and C4d deposition occurred linearly along the epithelial basement membrane. NP tissue extracts had significantly more anti-basement membrane antibodies than sera from CRSwNP and control patients (p<0.0001).ConclusionC5b-9, C4d and activated C1 were significantly increased locally in NP tissue. C5b-9 and C4d were almost universally deposited linearly along the basement membrane of NP tissue. Furthermore, activated C1 was best correlated with local immunoglobulin levels and C5a levels. Together, these data suggest that the classical pathway plays a major role in complement activation in CRS.

Teaser

Complement activation was elevated in CRSwNP tissue, and complement was deposited at the epithelial basement membrane. We conclude that the classical antibody-mediated complement pathway had a significant contribution to complement activation in nasal polyps.


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RhoA GTPase oxidation stimulates cell proliferation via nuclear factor-κB activation

Publication date: Available online 11 December 2016
Source:Free Radical Biology and Medicine
Author(s): Jae-Gyu Kim, Hyung-Joo Kwon, Guang Wu, Yohan Park, Jae-Yong Lee, Jaebong Kim, Sung-Chan Kim, Myoen Choe, Seung Goo Kang, Goo-Young Seo, Pyeung-Hyeun Kim, Jae-Bong Park
Reactive oxygen species (ROS) produced by many kinds of stimuli are essential for cellular signaling including cell proliferation. The dysregulation of ROS, therefore, is related to a variety of diseases including cancer. However, it was not clearly elucidated how ROS regulate cell proliferation and tumorigenesis. In this study, we investigated a mechanism by which the oxidation of RhoA GTPase regulates nuclear factor-κB (NF-κB) and cell proliferation. Hydrogen peroxide activated NF-κB and RhoA GTPase, but did not activate RhoA C16/20A mutant, an oxidation-resistant form. Remarkably, the oxidation of RhoA reduced its affinity towards RhoGDI, leading to the dissociation of RhoA-RhoGDI complex. Si-Vav2, a guanine nucleotide exchange factor (GEF), inhibited RhoA activation upon hydrogen peroxide. The oxidized RhoA (oxRhoA)-GTP was readily bound to IκB kinase γ (IKKγ), whereas oxidized RhoGDI did not bind to IKKγ. The oxRhoA-GTP bound to IKKγ activated IKKβ, leading to IκB phosphorylation and degradation, consequently NF-κB activation. Hydrogen peroxide induced cell proliferation, but RhoA C16/20A mutant suppressed cell proliferation and tumorigenesis. Conclusively, RhoA oxidation at Cys16/20 is critically involved in cell proliferation and tumorigenesis through NF-κB activation in response to ROS.

Graphical abstract

image


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Central Venous Catheter-Related Tachycardia in the Newborn: Case Report and Literature Review

Central venous access is an important aspect of neonatal intensive care management. Malpositioned central catheters have been reported to induce cardiac tachyarrhythmia in adult populations and there are case reports within the neonatal population. We present a case of a preterm neonate with a preexisting umbilical venous catheter (UVC), who then developed a supraventricular tachycardia (SVT). This was initially treated with intravenous adenosine with transient reversion. Catheter migration was subsequently detected, with the UVC tip located within the heart. Upon withdrawal of the UVC and a final dose of adenosine, the arrhythmia permanently resolved. Our literature review confirms that tachyarrhythmia is a rare but recognised neonatal complication of malpositioned central venous catheters. We recommend the immediate investigation of central catheter position when managing neonatal tachyarrhythmia, as catheter repositioning is an essential aspect of management.

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Growth hormone deficiency in children

Publication date: December 2016
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 30, Issue 6
Author(s): Flavia Prodam, Paolo Marzullo, Gianluca Aimaretti




http://ift.tt/2hkClLi

Keyword index

Publication date: December 2016
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 30, Issue 6





http://ift.tt/2hDM0t3

Mosaicism in health and disease — clones picking up speed

Nature Reviews Genetics. doi:10.1038/nrg.2016.145

Authors: Lars A. Forsberg, David Gisselsson & Jan P. Dumanski



http://ift.tt/2gCmgQh

Enhancing Mass Lesion of the Sphenoid: Atypical Presentation of Ongoing Pneumatization

Sinus pneumatization is a complex variable process that begins in early life and continues for many years. We present a case of a 6-year-old boy with progressive headaches and neurologic symptoms suggestive of intracranial pathology. The presence of enhancing tissue within the sphenoid sinus created a diagnostic dilemma which leads to a transsphenoidal biopsy. Knowledge of imaging characteristics associated with incomplete pneumatization can help differentiate it from more ominous skull base pathology and prevent unnecessary testing. We describe four-year imaging follow-up in a patient with incomplete pneumatization of the sphenoid sinus presenting as an enhancing mass lesion with subsequent follow-up imaging demonstrating gradual regression and increased aeration of the sphenoid sinus.

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Abdominal Wall Reconstruction Using Retrorectus Self-adhering Mesh: A Novel Approach

imageBackground: In abdominal wall reconstruction, the retrorectus plane offers an ideal location for mesh placement. Mesh fixation in this plane is often achieved using transfascial sutures, which risks entrapping intercostal nerves and causing significant pain, and takes time to place. A novel alternative is the use of sutureless self-adhering mesh. Although the use of this mesh in inguinal hernias has been well described, studies on its use in abdominal wall reconstruction are lacking. Methods: Consecutive patients who underwent ventral hernia repair with retrorectus mesh were reviewed. This included patients who received transfascially sutured mesh and those who received sutureless self-adhering mesh. All patients were followed up for at least 12 months. The amount of narcotics required by each patient postoperatively was calculated. Surgical-site occurrences (SSOs) and hernia recurrence and bulge were measured. Results: Twenty-six patients underwent abdominal wall reconstruction with retrorectus mesh. This included 12 patients with transfascially sutured mesh and 14 patients with self-adhering mesh. Mean follow-up was 600 days. Baseline characteristics were similar between the 2 groups. Patients receiving self-adhering mesh required significantly less narcotics than patients with transfascially sutured mesh. There were no significant differences in the rate of SSOs between the 2 groups. No hernia recurrences, bulges, or chronic pain occurred in either group. Conclusions: This is the first study to compare the outcomes of retrorectus self-adhering mesh and transfascially sutured mesh in abdominal wall reconstruction. Our results show low rates of SSO, recurrence, and bulge with both options, with significantly less acute pain with self-adhering mesh.

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