Hypovolemic shock after labial and lingual frenulectomy; a report of two cases

Lingual and labial frenulectomy are commonly performed as an outpatient procedure, either in an office setting or under general anesthesia. Frenulectomy is generally regarded by both otolaryngologists and dentists as a straightforward and low-risk procedure with limited evidence-based indications and similarly few contraindications. We describe two cases of hypovolemic shock occurring after outpatient frenulectomy requiring emergent interventions of cardiopulmonary resuscitation and blood transfusion.

http://ift.tt/2ulsET3

Can telemetry data obviate the need for sleep studies in Pierre Robin Sequence?

This study looks to correlate telemetry data gathered on patients with Pierre Robin Sequence (PRS) with sleep study data. Strong correlation might allow obstructive sleep apnea (OSA) to be reasonably predicted without the need for sleep study.

http://ift.tt/2vjuW2s

An innovative approach to improve ear, nose and throat surgical access for remote living Cape York Indigenous children

On a background of high rates of severe otitis media (OM) with associated hearing loss, children from the Torres Strait and Cape York region requiring ear, nose and throat (ENT) surgery, faced waiting times exceeding three years. After numerous clinical safety incidents were raised, indicating a failure of the current system to deliver appropriate care, the governing Hospital and Health service opted to deliver surgical care through an alternate process. ENT surgeries were performed on 16 consented children from two remote locations via the private health care system, funded by a health provider partnership.

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New process for 3D printing of cellulose

Publication date: Available online 13 July 2017
Source:Materials Today
Author(s): Laurie Donaldson




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The Effect of Glycopyrrolate on the Incidence of Hypotension and Vasopressor Requirement During Spinal Anesthesia for Cesarean Delivery: A Meta-analysis.

BACKGROUND: The objective of this meta-analysis was to determine the efficacy of glycopyrrolate at reducing spinal hypotension during cesarean delivery. METHODS: A literature search was performed to identify randomized controlled trials investigating the effect of glycopyrrolate on spinal-induced hypotension during cesarean delivery. Primary outcomes were intraoperative hypotension and vasopressor requirement (phenylephrine equivalents). Secondary outcomes included heart rate (HR), nausea and vomiting, dry mouth, and Apgar scores. Risk ratios (RRs), and mean differences (MDs) were calculated using random-effects modeling with 95% confidence intervals for primary outcomes and 99% confidence intervals for secondary outcomes. RESULTS: Five randomized controlled trials met our inclusion criteria. A total of 311 patients were included: 153 received glycopyrrolate and 158 placebo. The incidence of spinal-induced hypotension was no different with prophylactic glycopyrrolate compared to control (RR, 0.93 [0.71 1.21]; P = .59), but the total phenylephrine dose required was significantly reduced with glycopyrrolate (MD, -62.64 [micro]g [-107.61 to .17.66 [micro]g]; P = .006). The maximal HR achieved in the glycopyrrolate group was significantly higher compared to controls (MD, 15.85 bpm [5.40- 26.31]; P

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Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

BACKGROUND: Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. METHODS: Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. RESULTS: During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. CONCLUSIONS: : Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. (C) 2017 International Anesthesia Research Society

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Low End-Tidal Carbon Dioxide at the Onset of Emergent Trauma Surgery Is Associated With Nonsurvival: A Case Series.

BACKGROUND: End-tidal carbon dioxide (EtCO2) is a valuable marker of the return of adequate circulation following cardiac arrest due to medical causes. Previously, the prognostic value of capnography in trauma has been studied among limited populations in prehospital and emergency department settings. We aimed to investigate the relationship between early intraoperative EtCO2 and nonsurvival of patients undergoing emergency surgery at a level 1 academic trauma center as a case series. If there is a threshold below which survival was extremely unlikely, it might be useful in guiding decision-making in the early termination of futile resuscitative efforts. METHODS: Following institutional review board approval, a data set was created to investigate the relationship between EtCO2 values at the onset of emergent trauma surgery and nonsurvival. Patients who were admitted and transferred to the operating room (OR) directly from a resuscitation bay were identified using the Ryder Center trauma registry (October 1, 2013, to June 30, 2016). Electronic records from the hospital's anesthesia information management system were queried to identify the matching anesthesia records. The maximum EtCO2 values within 5 and 10 minutes of the onset of mechanical ventilation in the OR were determined for patients undergoing general anesthesia with mechanical ventilation. Patients were divided into 2 groups: those who were discharged from the hospital alive (survivors) and those who died in the hospital prior to discharge (nonsurvivors). The threshold EtCO2 giving a positive predictive value of 100% for in-hospital mortality was determined from a graphical analysis of the data. Association of determined threshold and mortality was analyzed using the 2-tailed Fisher exact test. RESULTS: There were 1135 patients who met the inclusion criteria. Within the first 5 minutes of the onset of mechanical ventilation in the OR, if the maximum EtCO2 value was

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Patient Survey of Referral From One Surgeon to Another to Reduce Maximum Waiting Time for Elective Surgery and Hours of Overutilized Operating Room Time.

BACKGROUND: Studies of shared (patient-provider) decision making for elective surgical care have examined both the decision whether to have surgery and patients' understanding of treatment options. We consider shared decision making applied to case scheduling, since implementation would reduce labor costs. METHODS: Study questions were presented in sequence of waiting times, starting with 4 workdays. "Assume the consultant surgeon (ie, the surgeon in charge) you met in clinic did not have time available to do your surgery within the next 4 workdays, but his/her colleague would have had time to do your surgery within the next 4 workdays. Would you have wanted to discuss with a member of the surgical team (eg, the scheduler or the surgeon) the availability of surgery with a different, equally qualified surgeon at Mayo Clinic who had time available within the next 4 workdays, on a date of your choosing?" There were 980 invited patients who underwent lung resection or cholecystectomy between 2011 and 2016; 135 respondents completed the study and 6 respondents dropped out after the study questions were displayed. RESULTS: The percentages of patients whose response to the study questions was "4 days" were 58.8% (40/68) among lung resection patients and 58.2% (39/67) among cholecystectomy patients. The 97.5% 2-sided confidence interval for the median maximum wait was 4 days to 4 days. Patients' choices for the waiting time sufficient to discuss having another surgeon perform the procedure did not differ between procedures (P = .91). Results were insensitive to patients' sex, age, travel time to hospital, or number of office visits before surgery (all P >= .20). CONCLUSIONS: Our results indicate that bringing up the option with the patient of changing surgeons when a colleague is available and has the operating room time to perform the procedure sooner is being respectful of most patients' individual preferences (ie, patient-centered). (C) 2017 International Anesthesia Research Society

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Abnormal Calcium Levels During Trauma Resuscitation Are Associated With Increased Mortality, Increased Blood Product Use, and Greater Hospital Resource Consumption: A Pilot Investigation.

BACKGROUND: Admission hypocalcemia predicts both massive transfusion and mortality in severely injured patients. However, the effect of calcium derangements during resuscitation remains unexplored. We hypothesize that any hypocalcemia or hypercalcemia (either primary or from overcorrection) in the first 24 hours after severe injury is associated with increased mortality. METHODS: All patients at our institution with massive transfusion protocol activation from January 2013 through December 2014 were identified. Patients transferred from another hospital, those not transfused, those with no ionized calcium (Ca2+) measured, and those who expired in the trauma bay were excluded. Hypocalcemia and hypercalcemia were defined as any level outside the normal range of Ca2+ at our institution (1-1.25 mmol/L). Receiver operator curve analysis was also used to further examine significant thresholds for both hypocalcemia and hypercalcemia. Hospital mortality was compared between groups. Secondary outcomes included advanced cardiovascular life support, damage control surgery, ventilator days, and intensive care unit days. RESULTS: The massive transfusion protocol was activated for 77 patients of whom 36 were excluded leaving 41 for analysis. Hypocalcemia occurred in 35 (85%) patients and hypercalcemia occurred in 9 (22%). Mortality was no different in hypocalcemia versus no hypocalcemia (29% vs 0%; P = .13) but was greater in hypercalcemia versus no hypercalcemia (78% vs 9%; P

http://ift.tt/2uYJsgr

Crisis Management in Acute Care Settings: Human Factors and Team Psychology in a High-Stakes Environment, 3rd ed.

No abstract available

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Implementation of a Standardized Transfusion Protocol for Cardiac Patients Treated With Venoarterial Extracorporeal Membrane Oxygenation Is Associated With Decreased Blood Component Utilization and May Improve Clinical Outcome.

BACKGROUND: Extracorporeal membrane oxygenation supplies oxygenated blood to the body supporting the heart and lungs. Survival rates of 20% to 50% are reported among patients receiving ECMO for cardiac arrest, severe cardiogenic shock, or failure to wean from cardiopulmonary bypass following cardiac surgery. Bleeding is one of the most common complications in ECMO patients due to coagulopathy, systemic anticoagulation, and the presence of large bore cannulas at systemic pressure. Absence of a standardized transfusion protocol in this population leads to inconsistent transfusion practices. Here, we assess a newly developed dedicated transfusion protocol in this clinical setting. METHODS: Data were retrospectively reviewed for the first 30 consecutive cardiac ECMO patients prior and post implementation of the ECMO transfusion protocol. Diagnoses, laboratory results, blood component utilization, and outcomes were collected and analyzed. RESULTS: Comorbidities were similar between the 2 eras, as well as the pre-ECMO ejection fraction (P = .568) and duration on ECMO (P = .278). Transfusion utilization data revealed statistically significant decreases in almost all blood components and a savings in blood component acquisition costs of 51% ($175, 970). In addition, an almost 2-fold increase in survival rate was observed in the post-ECMO transfusion protocol era (63% vs 33%; relative risk = 1.82; 95% confidence interval, 1.07-3.10; P = .028). CONCLUSIONS: Our data indicate that implementation of a standardized transfusion protocol, using more restrictive transfusion indications in cardiac ECMO patients, was associated with reduced blood product utilization, decreased complications, and improved survival. This multidepartmental approach facilitates better communication and adherence to consensus clinical decision making between intensive care unit, surgery, and transfusion service and optimizes care of complicated and acutely ill patients. (C) 2017 International Anesthesia Research Society

http://ift.tt/2uYpmTO

Stereotactic Ablative Radiation Therapy in Renal Cell Carcinoma: from oligometastatic to localized disease

Publication date: Available online 13 July 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Filippo Alongi, Stefano Arcangeli, Luca Triggiani, Rosario Mazzola, Michela Buglione di Monale e Bastia, Sergio Fersino, Anna Baiguini, Barbara Alicja Jereczek-Fossa, Stefano Maria Magrini
Renal Cell Carcinoma (RCC) has historically been considered a radioresistant cancer, and radiotherapy was usually delivered with a palliative goal. Stereotactic ablative radiotherapy (SABR) allows the delivery of high doses on small treatment volumes in a safe and effective way, thus opening the doors to new applicationsof radiotherapy both in the treatment of the primary and oligometastasic disease. Aim of the current review is to explore the state of art of SABR in the therapeutic approach to RCC.



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Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: the LUNA16 challenge

Publication date: Available online 13 July 2017
Source:Medical Image Analysis
Author(s): Arnaud Arindra Adiyoso Setio, Alberto Traverso, Thomas de Bel, Moira S.N. Berens, Cas van den Bogaard, Piergiorgio Cerello, Hao Chen, Qi Dou, Maria Evelina Fantacci, Bram Geurts, Robbert van der Gugten, Pheng Ann Heng, Bart Jansen, Michael M.J. de Kaste, Valentin Kotov, Jack Yu-Hung Lin, Jeroen T.M.C. Manders, Alexander Sóñora-Mengana, Juan Carlos García-Naranjo, Evgenia Papavasileiou, Mathias Prokop, Marco Saletta, Cornelia M Schaefer-Prokop, Ernst T. Scholten, Luuk Scholten, Miranda M. Snoeren, Ernesto Lopez Torres, Jef Vandemeulebroucke, Nicole Walasek, Guido C.A. Zuidhof, Bram van Ginneken, Colin Jacobs
Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems.

Graphical abstract

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Electrospun polymeric nanofibers: New horizons in drug delivery

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Shreya Thakkar, Manju Misra
Nanofibers obtained using electrospinning technique are being used since ages especially in fields of textile industry, sensors, filters, protective clothing and tissue engineering. Their use as drug delivery system is an emerging platform in the field of pharmaceuticals and now-a-days formulation scientists are paying great attention to the technology due to several advantages prime being easy modulation of drug release profile depending upon the properties of polymer/polymeric blends/other materials used. Although there are several reports citing the use of antibiotics-loaded nanofibers as wound dressing materials and as antimicrobial therapy in periodontics; still there is a good scope of expanding the horizon for its application in newer ailments. This article reviews various aspects related to loading and release of drug as such or in nano-particulate form to polymeric nanofibers by taking critical process parameters (CPPs) for electrospinning and critical material attributes (CMAs) into account. Commercially available products and electrospinning technologies are described in brief along with some of the patents related to their use as drug delivery systems. The main focus of this review is applicability of drug/drug nanoparticle loaded nanofibers in the management of diseases/disorders related to the brain, eye, ear, cardiovascular system, lungs and oral cavity. Use in diseases with higher mortality rates like diabetes, Acquired immunodeficiency syndrome (AIDS) and cancer is also described in brief.

Graphical abstract

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Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Mohammad Yahyaei, Faramarz Mehrnejad, Hossein Naderi-manesh, Ali Hossein Rezayan
Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS–CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel–FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery.

Graphical abstract

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Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes

Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Ning Li, Peng Quan, XiaoCao Wan, Chao Liu, Xiaochang Liu, Liang Fang
In this paper, based on the optimized formulation of olanzapine (OLN) transdermal patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT-IR and molecular modeling were conducted to elucidate the effect of SP on the release process of OLN from transdermal patch. Additionally, the action of SP on the percutaneous absorption process was probed using tape stripping transdermal experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular docking. The results showed that the hydrogen bonding interaction between OLN and pressure sensitive adhesive (PSA) was weakened by SP, which resulted in a decrease in the cohesive interaction between polymer chains and an increase in the formation of free volume of PSA, thus, the release of OLN from patch was promoted. Meanwhile, the OH groups of SP interacted with the polar head groups of the ceramides, which increased the fluidity of the skin lipids, thereby improved the ability of OLN percutaneous absorption. In summary, this study demonstrated that not only the release but also the percutaneous absorption processes were promoted by SP. This study provided comprehensive molecular level understanding on the effect of penetration enhancer on transdermal patch and strategies for rationally selection of chemical enhancer for transdermal drug delivery systems.

Graphical abstract

http://ift.tt/2tPmfih

Stereotactic Ablative Radiation Therapy in Renal Cell Carcinoma: from oligometastatic to localized disease

Publication date: Available online 13 July 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Filippo Alongi, Stefano Arcangeli, Luca Triggiani, Rosario Mazzola, Michela Buglione di Monale e Bastia, Sergio Fersino, Anna Baiguini, Barbara Alicja Jereczek-Fossa, Stefano Maria Magrini
Renal Cell Carcinoma (RCC) has historically been considered a radioresistant cancer, and radiotherapy was usually delivered with a palliative goal. Stereotactic ablative radiotherapy (SABR) allows the delivery of high doses on small treatment volumes in a safe and effective way, thus opening the doors to new applicationsof radiotherapy both in the treatment of the primary and oligometastasic disease. Aim of the current review is to explore the state of art of SABR in the therapeutic approach to RCC.



http://ift.tt/2tPq2ME

Immunohistochemical investigations on the expression of programmed cell death ligand 1, human leukocyte antigens G and E, and granzyme B in intraoral mucoepidermoid carcinoma

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Carla Mosconi, Diego Antônio Costa Arantes, Andréia Souza Gonçalves, Rita de Cássia Gonçalves Alencar, José Carlos Oliveira, Tarcília Aparecida Silva, Elismauro Francisco Mendonça, Aline Carvalho Batista
ObjectiveTo identify the expression of nonclassical human leukocyte antigen G and E (HLA-G and -E), programmed cell death ligand-1 (PD-L1) and granzyme B (GB) in intraoral mucoepidermoid carcinomas (MECs), and to assess whether such expressions are related to metastasis, survival, staging, tumor grade and number of GB-positive cells.DesignFor this cross-sectional study, samples of MEC (n=30) were selected and classified as low-grade (LG), intermediate-grade (IG) or high-grade (HG), according to the WHO grading system. HLA-G, -E and PD-L1 were identified by immunohistochemistry and quantified as the proportion of positive neoplastic cells. The density of GB+ cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level.ResultsExpressions of HLA-G, -E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. The quantitative analysis of the total percentage of positive neoplastic cells showed overexpression of this set of proteins in all MEC samples. The expression of these proteins and histological grading were positively correlated [HLA-G (LG=79% positive cells, IG=96%, HG=99%; p=0.0004), HLA-E (LG=70%, IG=96%, HG=99%; p<0.0001) and PD-L1 (LG=34%, IG=79%, HG=80%; p=0.01)]. No relationship was observed between the immunosuppressive proteins and other clinicopathological parameters. Low GB density was found in all MEC samples.ConclusionsThe augmented expression of HLA-G, -E and PD-L1 in the intraoral MEC might suggest a role of these molecules in the scape of neoplastic cells from immunosurveillance.



http://ift.tt/2ukV0N8

Enhanced Pru p 3 IgE binding activity by selective free fatty acid-interaction

Upon binding to certain lipids, the major peach allergen, Pru p 3, undergoes conformational changes thus exposing one dominant IgE epitope. This conformational change enhances the allergenicity of Pru p 3.

http://ift.tt/2t9lIsN

Iodine Supplementation for Premature Infants Does Not Improve IQ

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 277-279.


http://ift.tt/2viXOrp

Teprotumumab, an Antibody that Blocks the IGF-I Receptor, Causes Dramatic Improvement in Graves’ Orbitopathy

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 261-263.


http://ift.tt/2ulmIt4

For Papillary Thyroid Cancer Discovered During Pregnancy, Delayed Thyroid Surgery with Active Surveillance Is Appropriate

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 264-266.


http://ift.tt/2tSxc10

Low and High Maternal Iodine Intake During Pregnancy Are Associated with Child Neurobehavioral Outcomes

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 274-276.


http://ift.tt/2t9zzQ0

Postsurgically Hypothyroid Patients on Stable L-T4 Doses in Temperate Climates Have Higher Serum TSH Concentrations During the Coldest Months of the Year

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 280-282.


http://ift.tt/2vj8vdL

Specific Monoclonal Antibody Against Bcr/Abl Out-of-Frame Alternative Proteins as Diagnostic Tool in Chronic Myelogenous Leukemia Patients

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


http://ift.tt/2tSiJCg

Digital evaluation of nasal changes induced by rapid maxillary expansion with different anchorage and appliance design

Abstract

Background

Scientific evidence showed that rapid maxillary expansion (RME) affects naso-maxillary complex, increasing nasal width and volume. This study aimed to evaluate nasal changes induced by rapid maxillary expansion with different anchorage and appliance design by using low dose and cone beam computed tomography.

Methods

A total of 44 patients (20 males, mean age 8y 8 m ± 1y 2 m; 24 females mean age 8y 2 m ± 1y 4 m) were included in the investigation and divided into three groups according to the appliance: Hyrax-type expander anchored to permanent teeth, modified Hyrax-type expander anchored to deciduous teeth, modified Haas-type expander anchored to deciduous teeth. Maxillary expansion was performed until overcorrection and the expander was passively kept in situ for 7 months at least. All patients had three-dimensional imaging before expansion (T0) and after the retention period (T1). Nasal floor width, nasal wall width, maxillary inter-molar width were measured by means of Mimics software. The paired sample t-test was employed to assess the significance of the differences between the time points; the analysis of variance test (ANOVA) was used to compare differences between groups.

Results

The statistical analysis revealed significant differences between T0 and T1 for each recorded measurement in each group; no significant differences were found by comparing groups.

Conclusions

Rapid maxillary expansion produces a significant skeletal transverse expansion of nasal region in growing patients. No significant differences in nasal effects are expected when the appliance is anchored onto deciduous teeth, with or without the palatal acrylic coverage.

http://ift.tt/2ulbXqR

Genetic polymorphism of scrA gene of Streptococcus mutans isolates is not associated with biofilm formation in severe early childhood caries

Abstract

Background

To explore and analyse the association between biofilm and the genetic polymorphisms of scrA gene of EnzymeIIscr found in clinical isolates of Streptococcus mutans (S. mutans) from severe early childhood caries (S-ECC) in 3 years old children.

Methods

Clinical strains of S. mutans were conserved from a previous study. Thirty strains of S. mutans from the S-ECC group and 30 strains of S. mutans from the caries free (CF) group were selected. Biomass and viability of biofilm formed by the strains were evaluated by crystal violet and alamar blue assay. Genomic DNA was extracted from the S. mutans isolates. PCR was conducted to amplify scrA gene. After purified and sequenced the PCR products, BioEdit sofeware was used to analyse the sequence results. A chi-square test was used to compare the results.

Results

Compared to the CF group, the biomass of S-ECC group was higher (P = 0.0424). However, the viability of the two groups showed no significant difference. All 60 clinically isolated S. mutans strains had a 1995 base pair (bp) scrA gene. Forty-nine point mutations were identified in scrA from the 60 clinical isolates. There were 17 missense point mutations at the 10, 65, 103, 284, 289, 925, 1444, 1487, 1494, 1508, 1553, 1576, 1786, 1822, 1863, 1886, and 1925 bp positions. The other 32 mutations were silent point mutations. No positions were found at active sites of ScrA. The statistic analyse showed no significant missense mutation rates between the two groups.

Conclusions

There was no association between biofilm and genetic polymorphisms of scrA from S. mutans with S-ECC in 3 years old children.

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Extrathyroidal Extension Predicts Decreased Survival in Thyroid Cancer Patients

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 271-273.


http://ift.tt/2sWG9oT

Teprotumumab, an Antibody that Blocks the IGF-I Receptor, Causes Dramatic Improvement in Graves’ Orbitopathy

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 261-263.


http://ift.tt/2ulmIt4

For Papillary Thyroid Cancer Discovered During Pregnancy, Delayed Thyroid Surgery with Active Surveillance Is Appropriate

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 264-266.


http://ift.tt/2tSxc10

Low and High Maternal Iodine Intake During Pregnancy Are Associated with Child Neurobehavioral Outcomes

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 274-276.


http://ift.tt/2t9zzQ0

Can Imaging with FDG-PET Help Exclude Malignancy in Cytologically Indeterminate Thyroid Nodules?

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 267-270.


http://ift.tt/2tSeXsm

Postsurgically Hypothyroid Patients on Stable L-T4 Doses in Temperate Climates Have Higher Serum TSH Concentrations During the Coldest Months of the Year

Clinical Thyroidology Jul 2017, Vol. 29, No. 7: 280-282.


http://ift.tt/2vj8vdL

Acute facial nerve paralysis in children,............................................................................................................................................ Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature by Latha M Sneha via CHRISMED Journal of Health and Research : 2014 - 1(4) Latha M Sneha, Raichel Priyanka, Shanthini Thanga Tamilselvan, Julius Xavier Scott CHRISMED Journal of Health and Research 2017 4(3):209-211 Infections, inflammatory, and autoimmune conditions are the well-recognized etiologies of acute facial nerve paralysis in children. Bell's palsy is idiopathic peripheral facial nerve palsy. Cranial neuropathies do occur in children due to the central nervous system involvement by malignancies but uncommon in pediatric acute lymphoblastic leukemias and even rarer in acute myeloid leukemias (AMLs). We report a case of a 13-year-old girl who presented with acute facial nerve palsy, wa

The common etiology associated with acute facial nerve paralysis in children are otitis media, mastoiditis, viral infections such as herpes, varicella, mumps, HIV, meningitis, encephalitis, mycoplasma, Lyme disease, and inflammatory conditions such as vasculitis, Henoch–Schonlein purpura, Kawasaki syndrome, Gullain–Barre syndrome, and hypertension.[3]

Seventy percent of the children with acute lower motor neuron facial paralysis have a favorable prognosis and it resolves spontaneously within 3 months without any sequela. In 40%–75% of children, cause of unilateral facial paralysis is idiopathic, described as Bell's palsy and most of them have a positive history of viral illness 2–3 weeks preceding the neurological manifestations. The use of steroids to reduce the duration of paralysis and reduce the risk of long-term impairment was based on adult studies though the benefits of steroids in children is yet to be proven.[4] Due to the self-resolving nature of the idiopathic variety of the facial palsy seen in children, the neurological manifestations of leukemia as an etiology is never thought of. Steroids, when commonly prescribed in such cases causes a partial recovery thereby masking the primary pathology and adds to the diagnostic dilemma.

The frequency of symptomatic facial palsy has been found to be higher in the younger age group when compared to the idiopathic variety.[5]

AML accounts for 15% of all leukemia and presents with symptoms of prolonged fever, hepatosplenomegaly, and skin or mucocutaneous bleeds. When focal masses of immature myeloid cells from the granulocytic lineage infiltrate the soft tissues and bones, they are called granulocytic sarcomas or chloromas and occur in 5% of cases of AML. It is postulated that the granulocytic sarcomas traverse through the haversian canals from the bone marrow and gets deposited in the subperiosteum to form soft tissue masses.[6]

Granulocytic sarcomas may manifest concurrently with the disease or during remission or relapse. However, when sarcomas precede the disease in peripheral blood or marrow, it often poses a diagnostic challenge, more so, if cranial neuropathies are caused by unidentifiable chloromas as in our case. Facial paralysis resulting from leukemic infiltration, though rare, occurs during the relapse of the disease or as a complication primary disease, but it is not a well-recognized presenting symptom of childhood leukemia. Diagnostic delays of 1 month have been reported when facial nerve palsy was the isolated manifestation of AML in children.[7] Otomastoiditis due to the leukemic infiltration of the temporal bone has been attributed to the facial nerve paralysis. MRI with contrast of the facial nerve canal helps in identifying the facial nerve enhancement. However, the clinical findings of facial nerve paralysis were not always associated with radiological findings in most of the cases.[7]

Baek et al. have reported 11 children who had facial nerve paralysis as isolated feature of AML. Brain imaging studies showed mastoiditis in four of them and chloroma was identified in five of them. Six of them did not have blast in the CSF. Facial nerve palsy improved within a mean period of 1–6 months of chemotherapy.[7] Rohit et al. have reported a case of 13-year-old girl-AML with t(8:21) positivity who presented with bilateral proptosis and facial nerve palsy.[8]

When leukemic children presented with cranial neuropathies, the treatment included systemic and intrathecal chemotherapy with whole brain irradiation. However, Baek et al. recommend allogenic bone marrow transplant, avoiding whole brain irradiation in children to reduce the development of secondary malignancies and to prevent the long-term sequelae on cognitive and endocrine function.

Due to the self-resolving nature of the idiopathic variety of facial nerve palsy, when these children present to general physicians or neurologists, the diagnosis of leukemia is overlooked. Gradual progression of the paralysis beyond 3 weeks should warrant additional investigations to rule out the etiology.

CASE REPORT

Year : 2017  |  Volume : 4  |  Issue : 3  |  Page : 209-211

Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature

Latha M Sneha¹, Raichel Priyanka², Shanthini Thanga Tamilselvan², Julius Xavier Scott^3
1 Department of Pediatrics, Division of Pediatric Hemato Oncology, Sri Ramachandra University, Chennai, Tamil Nadu, India
² Department of Pediatrics, Sri Ramachandra University, Chennai, Tamil Nadu, India
³ Division of Pediatric Hemato Oncology, Sri Ramachandra University, Chennai, Tamil Nadu, India

Date of Web Publication

13-Jul-2017

Correspondence Address:
Latha M Sneha
Division of Pediatric Hemato Oncology, Sri Ramachandra University, No. 1, Ramachandra Nagar, Porur, Chennai - 600 116, Tamil Nadu 
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/cjhr.cjhr_123_16

Abstract

Infections, inflammatory, and autoimmune conditions are the well-recognized etiologies of acute facial nerve paralysis in children. Bell's palsy is idiopathic peripheral facial nerve palsy. Cranial neuropathies do occur in children due to the central nervous system involvement by malignancies but uncommon in pediatric acute lymphoblastic leukemias and even rarer in acute myeloid leukemias (AMLs). We report a case of a 13-year-old girl who presented with acute facial nerve palsy, was being treated as Bell's palsy elsewhere and was later diagnosed to have AML.

Keywords: Acute myeloid leukemia, Bell's palsy, child

How to cite this article: Sneha LM, Priyanka R, Tamilselvan ST, Scott JX. Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature. CHRISMED J Health Res 2017;4:209-11

How to cite this URL: Sneha LM, Priyanka R, Tamilselvan ST, Scott JX. Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature. CHRISMED J Health Res [serial online] 2017 [cited 2017 Jul 14];4:209-11. Available from: http://www.cjhr.org/text.asp?2017/4/3/209/210478

Introduction

Acute, peripheral facial palsy can be presenting feature of infections, inflammatory, and autoimmune conditions and has a good prognosis in children. The incidence of facial paralysis in children <10 years of age is reported to be 2.7/100,000.^[1] Majority of them are unilateral, idiopathic, and termed Bell's palsy. A diagnosis of exclusion, Bell's palsy accounts for 42%–85% of cases in children with facial nerve paralysis.^[2] Although association of facial palsies in malignancies is well reported, facial paralysis is not a well-recognized presenting feature of leukemias in children, especially in acute myeloid leukemia (AML). The presence of Bell's palsy in children warrants a complete evaluation to rule out leptomeningeal diseases. We report a case of an adolescent girl who presented with acute facial nerve palsy, treated as Bell's palsy elsewhere and was later diagnosed to have AML.

Case Report

A 13-year-old girl presented with acute onset of right-sided facial nerve palsy of 2 weeks duration. She was diagnosed to have idiopathic Bell's palsy elsewhere and was being treated symptomatically with physiotherapy and oral steroids with no improvement in symptoms. She had no constitutional symptoms of fever, anorexia or fatigue, bone pain, mucocutaneous, or skin bleeds. In view of persistent symptoms, she was referred to a higher center for further evaluation. Examination revealed a right-sided lower motor neuron facial nerve palsy [Figure 1], without hepatosplenomegaly or lymphadenopathy. Central nervous system examination and rest of the systemic examination were normal. Investigations revealed hemoglobin 5.9 g/dl, total leukocyte count 14,900/μL (polymorphs: 64.1%, lymphocytes 30.3%), and platelet count 83,000/μL. Peripheral smear revealed leukocytosis with increase in blasts (50%) with  Auer rods ^{More Details} along with thrombocytopenia [Figure 2].

Figure 1: Right-sided lower motor neuron palsy Click here to view

Figure 2: Peripheral smear showing blasts with Auer rods Click here to view

Bone marrow aspiration showed hypercellular marrow with 58% blasts, promyelocytes - nil, myelocytes - 9, metamyelocytes - 9, neutrophil - 3, eosinophil - 2, band - 4, lymphocytes - 9, monocytes - nil, and plasma cells - 1 [Figure 3]. Cerebrospinal fluid (CSF) analysis was negative for malignant cells. Flow cytometry revealed blasts positive for CD33, cytoplasmic myeloperoxidase, and Human leukocyte antigen –D related (HLA-DR). Magnetic resonance imaging (MRI) brain, MRI angiogram, and venogram were normal. Cytogenetics was negative for t(8:21), inversion 16, t(9:11), and t(15:17). The girl was diagnosed as AML M0. She was started on chemotherapy and after the first cycle of chemotherapy, the bone marrow is in remission and she had partial resolution of facial nerve palsy.

Figure 3: Bone marrow aspirate showing hypercellular marrow with increased blasts 58% Click here to view

Discussion

The common etiology associated with acute facial nerve paralysis in children are otitis media, mastoiditis, viral infections such as herpes, varicella, mumps, HIV, meningitis, encephalitis, mycoplasma, Lyme disease, and inflammatory conditions such as vasculitis, Henoch–Schonlein purpura, Kawasaki syndrome, Gullain–Barre syndrome, and hypertension.^[3]

Seventy percent of the children with acute lower motor neuron facial paralysis have a favorable prognosis and it resolves spontaneously within 3 months without any sequela. In 40%–75% of children, cause of unilateral facial paralysis is idiopathic, described as Bell's palsy and most of them have a positive history of viral illness 2–3 weeks preceding the neurological manifestations. The use of steroids to reduce the duration of paralysis and reduce the risk of long-term impairment was based on adult studies though the benefits of steroids in children is yet to be proven.^[4] Due to the self-resolving nature of the idiopathic variety of the facial palsy seen in children, the neurological manifestations of leukemia as an etiology is never thought of. Steroids, when commonly prescribed in such cases causes a partial recovery thereby masking the primary pathology and adds to the diagnostic dilemma.

The frequency of symptomatic facial palsy has been found to be higher in the younger age group when compared to the idiopathic variety.^[5]

AML accounts for 15% of all leukemia and presents with symptoms of prolonged fever, hepatosplenomegaly, and skin or mucocutaneous bleeds. When focal masses of immature myeloid cells from the granulocytic lineage infiltrate the soft tissues and bones, they are called granulocytic sarcomas or chloromas and occur in 5% of cases of AML. It is postulated that the granulocytic sarcomas traverse through the haversian canals from the bone marrow and gets deposited in the subperiosteum to form soft tissue masses.^[6]

Granulocytic sarcomas may manifest concurrently with the disease or during remission or relapse. However, when sarcomas precede the disease in peripheral blood or marrow, it often poses a diagnostic challenge, more so, if cranial neuropathies are caused by unidentifiable chloromas as in our case. Facial paralysis resulting from leukemic infiltration, though rare, occurs during the relapse of the disease or as a complication primary disease, but it is not a well-recognized presenting symptom of childhood leukemia. Diagnostic delays of 1 month have been reported when facial nerve palsy was the isolated manifestation of AML in children.^[7] Otomastoiditis due to the leukemic infiltration of the temporal bone has been attributed to the facial nerve paralysis. MRI with contrast of the facial nerve canal helps in identifying the facial nerve enhancement. However, the clinical findings of facial nerve paralysis were not always associated with radiological findings in most of the cases.^[7]

Baek et al. have reported 11 children who had facial nerve paralysis as isolated feature of AML. Brain imaging studies showed mastoiditis in four of them and chloroma was identified in five of them. Six of them did not have blast in the CSF. Facial nerve palsy improved within a mean period of 1–6 months of chemotherapy.^[7] Rohit et al. have reported a case of 13-year-old girl-AML with t(8:21) positivity who presented with bilateral proptosis and facial nerve palsy.^[8]

When leukemic children presented with cranial neuropathies, the treatment included systemic and intrathecal chemotherapy with whole brain irradiation. However, Baek et al. recommend allogenic bone marrow transplant, avoiding whole brain irradiation in children to reduce the development of secondary malignancies and to prevent the long-term sequelae on cognitive and endocrine function.

Due to the self-resolving nature of the idiopathic variety of facial nerve palsy, when these children present to general physicians or neurologists, the diagnosis of leukemia is overlooked. Gradual progression of the paralysis beyond 3 weeks should warrant additional investigations to rule out the etiology.

Conclusion

While managing young children with acute lower motor neuron facial nerve palsy, neurologists and general physicians should have an index of suspicion for the neurological manifestations of acute leukemia and hence complete blood counts, peripheral smear and a bone marrow study if needed should be a part of the work up for etiology in such cases. The routine use of steroids may result in partial remission and can cause diagnostic delays.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

References

1.	Singhi P, Jain V. Bell's palsy in children. Semin Pediatr Neurol 2003;10:289-97.   [PUBMED]
2.	May M, Fria TJ, Blumenthal F, Curtin H. Facial paralysis in children: Differential diagnosis. Otolaryngol Head Neck Surg 1981;89:841-8.
3.	Ciorba A, Corazzi V, Conz V, Bianchini C, Aimoni C. Facial nerve paralysis in children. World J Clin Cases 2015;3:973-9.
4.	Unüvar E, Oguz F, Sidal M, Kiliç A. Corticosteroid treatment of childhood Bell's palsy. Pediatr Neurol 1999;21:814-6.
5.	Krishnamurthy S, Weinstock AL, Smith SH, Duffner PK. Facial palsy, an unusual presenting feature of childhood leukemia. Pediatr Neurol 2002;27:68-70.
6.	Stein-Wexler R, Wootton-Gorges SL, West DC. Orbital granulocytic sarcoma: An unusual presentation of acute myelocytic leukemia. Pediatr Radiol 2003;33:136-9.
7.	Baek HJ, Han DK, Kim YO, Choi IS, Hwang TJ, Kook H. Facial palsy as the presenting symptom of acute myeloid leukemia in children: Three cases with stem cell transplantations. Korean J Pediatr 2009;52:713-6.
8.	Rohit K, Jitender MK, Atul S, Soumya S. The paradox of recurrent with rare: A rare case of bilateral proptosis and facial palsy in acute myeloid leukemia with recurrent cytogenetic translocation t(8:21). Int J Appl Basic Med Res 2015;5:76-8.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Concomitant Epstein-Barr Virus-associated smooth muscle tumor and granulomatous inflammation of the liver

Publication date: Available online 13 July 2017
Source:Pathology - Research and Practice
Author(s): Nhu Thuy Can, James Grenert, Poonam Vohra
Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions.



http://ift.tt/2sWuI08

Comparison of Oncotype DX® Recurrence Score® with other risk assessment tools including the Nottingham Prognostic Index in the identification of patients with low-risk invasive breast cancer

Abstract

Oncotype DX® is a gene expression assay that quantifies the risk of distant recurrence in patients with hormone receptor positive early breast cancer, publicly funded in Ireland since 2011. The aim of this study was to correlate Oncotype DX® risk groupings with traditional histopathological parameters and the results of other risk assessment tools including Recurrence Score-Pathology-Clinical (RSPC), Adjuvant Risk Index (Adj RI), Nottingham Prognostic Index (NPI) and the Adjuvant! Online 10-year score (AO). Patients were retrospectively identified from the histopathology databases of two Irish hospitals and patient and tumour characteristics collated. Associations between categorical variables were evaluated with Pearson's chi-square test. Correlations were calculated using Spearman's correlation coefficient and concordance using Lin's concordance correlation coefficient. Statistical analysis was performed using SPSS software, version 22.0.

In our 300 patient cohort, Oncotype DX® classified 59.7% (n = 179) as low, 30% (n = 90) as intermediate, and 10.3% (n = 31) as high risk. Overall concordance between the RS and RSPC, Adj RI, NPI, and AO was 67.3% (n = 202), 56.3% (n = 169), 59% (n = 177), and 36.3% (n = 109), respectively. All risk assessment tools classified the majority of patients as low risk apart from the AO 10-year score, with RSPC classifying the highest number of patients as low risk. This study demonstrates that there is good correlation between the RS and scores obtained using alternative risk tools. Concordance with NPI is strong, particularly in the low-risk group. NPI, calculated from traditional clinicopathological characteristics, is a reliable alternative to Oncotype DX® in the identification of low-risk patients who may avoid adjuvant chemotherapy.

http://ift.tt/2upgBEZ

The effects of uvulopalatal flap operation on speech nasalance and the acoustic parameters of the final nasal consonants

The acoustic characteristics of voice are determined by the source of the sound and shape of the vocal tract. Various anatomical changes after uvulopalatal flap (UPF) operation can change nasalance and/or other voice characteristics. Our aim was to explore the possible effects of UPF creation on speech nasalance and the resonatory features of the final nasal consonants, and thus voice characteristics.

http://ift.tt/2ufa2Vm

The effects of uvulopalatal flap operation on speech nasalance and the acoustic parameters of the final nasal consonants

The acoustic characteristics of voice are determined by the source of the sound and shape of the vocal tract. Various anatomical changes after uvulopalatal flap (UPF) operation can change nasalance and/or other voice characteristics. Our aim was to explore the possible effects of UPF creation on speech nasalance and the resonatory features of the final nasal consonants, and thus voice characteristics.

http://ift.tt/2ufa2Vm

Anti-IL-21 monoclonal antibody combined with liraglutide effectively reverses established hyperglycemia in mouse models of type 1 diabetes

Publication date: Available online 12 July 2017
Source:Journal of Autoimmunity
Author(s): Anna K. Rydén, Nikole R. Perdue, Philippe P. Pagni, Claire B. Gibson, Sowbarnika S. Ratliff, Rikke K. Kirk, Travis J. Friesen, Claus Haase, Ken Coppieters, Matthias G. von Herrath, Tamar E. Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D. We report here that treatment with anti-IL-21 monoclonal antibody delays diabetes onset in the spontaneous non-obese diabetic (NOD) and NOD.scid adoptive transfer models, while its effect in reversing recent-onset hyperglycemia is limited. However, the combination of anti-IL-21 plus the GLP-1R agonist liraglutide is effective in reversing established disease compared to either monotherapy in both the NOD and rat insulin promotor-lymphocytic choriomeningitis virus glycoprotein (RIP-LCMV-GP) models of autoimmune diabetes. Enhanced efficacy is particularly evident in severely hyperglycemic mice, with return to normoglycemia remaining stable for the majority of mice even after therapy is withdrawn. Importantly, increased beta cell proliferation does not appear to be the predominant mechanism. In conclusion, combination therapy with anti-IL-21 and liraglutide is able to consistently reverse disease in mouse models of T1D. The observed effects rival the most effective experimental disease-modifying treatments tested in preclinical studies.



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Novel therapeutic targets for inflammatory bowel disease

Publication date: Available online 12 July 2017
Source:Journal of Autoimmunity
Author(s): Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy. The treat to target approach possibly correlates with minor risk for complications associated with IBD, specially surgery and cancer.The most studied inflammatory pathway in IBD, is described to be dependent of the pro-inflammatory cytokine tumor necrosis factor-alfa (TNF-α), and compose the first line studies for development of biological drugs, in this case, targeting specifically the action of TNF-α. Even though, the use of anti-TNFs drugs are associated with improvement of the inflammation in some patients, a great portion do not respond at first or lose response over time. These findings made clear about the possibility of other mechanisms involved in perpetuating the chronic inflammatory state.Many years of intensive research have led to the identification of different inflammatory pathways that form the basis of the intensive drug development that we are experiencing today. These novel drugs include agents that target leukocyte trafficking, Interleukin (IL) 23, Janus kinases (JAK), Sphingosine 1 phosphate (S1P) and Smad7, an inhibitor of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1). In this manuscript, we aim to review the most promising late-stage drug candidates for the treatment of IBD.



http://ift.tt/2tl6gFq

Epithelial-mesenchymal transition of human lung adenocarcinoma A549 cells up-regulates cytokine production upon LPS stimulation

Publication date: Available online 13 July 2017
Source:Allergology International
Author(s): Takafumi Kato, Koichi Kobayashi, Maho Suzukawa, Minako Saito, Kenichi Okuda, Kazuya Koyama, Sayaka Igarashi, Sayaka Arakawa, Nobuharu Ohshima, Hirotoshi Matsui, Takahide Nagase, Ken Ohta




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A novel function for Cactus/I{kappa}B inhibitor to promote Dl nuclear localization and activity in the Drosophila embryo [RESEARCH REPORT]

Maira Arruda Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Mascarello Bisch, Stanislav Shvartsman, and Helena Marcolla Araujo

The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFB effector Dorsal. Here we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and Dorsal target genes. Quantitative analysis using a series of loss and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently respective to Cactus fluctuations. In lateral and dorsal embryo domains loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as an NFB inhibitor, ensuring a correct response to Toll signals.

http://ift.tt/2t9mExu

Cellular heterogeneity in the ureteric progenitor niche and distinct profiles of branching morphogenesis in organ development [TECHNIQUES AND RESOURCES]

Elisabeth A. Rutledge, Jean-Denis Benazet, and Andrew P. McMahon

Branching morphogenesis creates arborized epithelial networks. In the mammalian kidney, an epithelial progenitor pool at ureteric branch tips (UBT) creates the urine-transporting collecting system. Using region-specific mouse reporter strains, we performed an RNA-seq screen, identifying tip and stalk enriched gene sets in the developing collecting duct system. Detailed in situ hybridization studies of tip-enriched predictions identified UBT-enriched gene sets conserved between the mouse and human kidney. Comparative spatial analysis of their UBT niche expression highlighted distinct patterns of gene expression revealing novel molecular heterogeneity within the UBT progenitor population. To identify kidney-specific and shared programs of branching morphogenesis, comparative expression studies on the developing mouse lung were combined with in silico analysis of the developing mouse salivary gland. These studies highlight a shared gene set with multi-organ tip enrichment and a gene set specific to UBTs. This comprehensive analysis extends our current understanding of the ureteric branch tip niche.

http://ift.tt/2vj84ju

Cas9-mediated excision of Nematostella brachyury disrupts endoderm development, pharynx formation, and oral-aboral patterning [RESEARCH ARTICLE]

Marc D. Servetnick, Bailey Steinworth, Leslie S. Babonis, David Simmons, Miguel Salinas-Saavedra, and Mark Q. Martindale

The mesoderm was a key novelty in animal evolution, though we understand little of how mesoderm arose. brachyury, the founding member of the T-box gene family, is a key gene in chordate mesoderm development. However, the brachyury gene was present in the common ancestor of fungi and animals, long before mesoderm appeared. To explore ancestral roles of brachyury prior to the evolution of definitive mesoderm, we excised the gene using CRISPR/Cas9 in the diploblastic cnidarian Nematostella vectensis. Nvbrachyury is normally expressed in precursors of the pharynx, which separates endoderm from ectoderm. In knockout embryos, the pharynx does not form, embryos fail to elongate, and endoderm organization, ectodermal cell polarity and patterning along the oral-aboral axis are disrupted. Expression of many genes both inside and outside the Nvbrachyury expression domain is affected, including downregulation of Wnt genes at the oral pole. Our results point to an ancient role for brachyury in morphogenesis, cell polarity, and patterning both ectodermal and endodermal derivatives along the primary body axis.

http://ift.tt/2ukP5rx

Genome-wide analysis of facial skeletal regionalization in zebrafish [TECHNIQUES AND RESOURCES]

Amjad Askary, Pengfei Xu, Lindsey Barske, Maxwell Bay, Paul Bump, Bartosz Balczerski, Michael A. Bonaguidi, and J. Gage Crump

Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventral-most regions. Analysis of co-variance across multiple sequencing experiments further reveals clusters of co-regulated genes, with in situ hybridization confirming the domain-specific expression of novel genes. We then created loss-of-function alleles for 12 genes and uncovered antagonistic functions of two new Edn1 targets, follistatin a (fsta) and emx2, in regulating cartilaginous joints in the hyoid arch. Our unbiased discovery and functional analysis of genes with regional expression in zebrafish arch CNCCs reveals complex regulation by Edn1 and points to novel candidates for craniofacial disorders.

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