Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF followi...
http://ift.tt/2wwOi8I
Τρίτη 22 Αυγούστου 2017
Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF followi...
http://ift.tt/2wwOi8I
Constructing a patient-specific computer model of the upper airway in sleep apnea patients
Objective
The use of computer simulation to develop a high-fidelity model has been proposed as a novel and cost-effective alternative to help guide therapeutic intervention in sleep apnea surgery. We describe a computer model based on patient-specific anatomy of obstructive sleep apnea (OSA) subjects wherein the percentage and sites of upper airway collapse are compared to findings on drug-induced sleep endoscopy (DISE).
Study Design
Basic science computer model generation.
Methods
Three-dimensional finite element techniques were undertaken for model development in a pilot study of four OSA patients. Magnetic resonance imaging was used to capture patient anatomy and software employed to outline critical anatomical structures. A finite-element mesh was applied to the volume enclosed by each structure. Linear and hyperelastic soft-tissue properties for various subsites (tonsils, uvula, soft palate, and tongue base) were derived using an inverse finite-element technique from surgical specimens. Each model underwent computer simulation to determine the degree of displacement on various structures within the upper airway, and these findings were compared to DISE exams performed on the four study patients.
Results
Computer simulation predictions for percentage of airway collapse and site of maximal collapse show agreement with observed results seen on endoscopic visualization.
Conclusion
Modeling the upper airway in OSA patients is feasible and holds promise in aiding patient-specific surgical treatment.
Level of Evidence
NA. Laryngoscope, 2017
http://ift.tt/2wDJPQQ
Efficacy and rebound rates in propranolol-treated subglottic hemangioma: A literature review
Objective
Propranolol has recently become the treatment of choice for management of subglottic and airway hemangiomas. This literature review aimed to determine the success rate of propranolol for managing these lesions as well as the rate of rebound growth following propranolol treatment cessation.
Study Design
Literature search involving MEDLINE and Scopus to identify English-language articles.
Methods
Studies were identified using hemangioma, subglottic or airway, and propranolol for search terms. Studies were eligible for inclusion if they reported the treatment used, individual deidentified patient data, and contained patients without medical or surgical treatment prior to propranolol therapy
Results
Initial review included 107 abstracts. Twenty-four articles including case reports and case series met inclusion criteria and were included in the qualitative analysis. Forty-nine patients were included. Twenty-eight (57%) were treated with propranolol alone, and 20 (41%) were treated with a combination of propranolol and a corticosteroid. Thirty-seven (76%) of patients were treated with a dose of 2 mg/kg/d of propranolol. The initial treatment was successful in 43 (88%) of patients. Rebound growth occurred in four (9%) patients. Overall, six (12%) patients underwent surgical resection.
Conclusions
Propranolol is efficacious for treating subglottic hemangiomas. Rebound growth does occur in a small subset of patients during the propranolol wean. Close observation for children during weaning of propranolol therapy for subglottic hemangioma is essential. Adjunctive management strategies need to be used in patients with rebound growth. Laryngoscope, 2017
http://ift.tt/2vdvFT5
Peristomal skin complications: what dermatologists need to know
Abstract
A stoma is an artificial opening to the skin formed when a part of the gastrointestinal tract is resected and opened to the skin in order to divert the bowel content to the skin surface. The incidence of stomal and peristomal complication varies from 30 to 67% with a significant negative impact on patient quality of life. Despite their prevalence, care providers tend to show insufficient awareness of peristomal skin complications, and research-based evidence related to peristomal skin complication and management options particularly in dermatology literature is sparse. This article will present a comprehensive review of peristomal skin complications in classification, clinical presentation, causes, prevention, and management aiming at increasing knowledge about this topic.
http://ift.tt/2xbmq7k
What's new in dermoscopy of Bowen's disease: two new dermoscopic signs and its differential diagnosis
Abstract
Background
Clinical and dermoscopic features of Bowen's disease (BD) show great diversity. Some lesions of BD are often difficult to be differentiated from seborrheic keratosis, actinic keratosis, lichen planus-like keratosis, etc. It is necessary to fully describe the dermoscopic features of the disease, considering differential diagnosis.
Objective
To describe the dermoscopic feautres of Bowen's disease and summarize the dermoscopic differential diagnosis of the disease.
Patients and methods
Altogether 146 lesions with a histopathological diagnosis of Bowen's disease were consecutively included in this study. All the lesions were imaged with dermoscopy and analyzed for dermoscopic features.
Results
A total of 146 lesions were analyzed. The dermoscopic features most frequently observed in our series of lesions were scales (78.8%), glomerular vessels (69.2%), yellow crusts (56.8%), focal hemorrhage (55.5%), focal/multifocal hypopigmentation (44.5%), and linear irregular vessels (42.5%). Besides, we found two new dermoscopic signs in BD: the double-edge sign (30.1%) and the clusters of brown structureless areas (38.4%).
Conclusion
Bowen's disease presents a variety of dermoscopic features. The recognition of two new dermoscopic signs of BD and fully understanding its dermoscopic features will help us in differential diagnosis.
http://ift.tt/2xbkUC6
The Impact of Waiting List Bmi Changes on the Short-Term Outcomes of Lung Transplantation.
http://ift.tt/2v4pXqr
Protective efficacy of a hydroxy fatty acid against gastric Helicobacter infections
Abstract
Background
We have previously revealed that omega-3 polyunsaturated fatty acids can prevent Helicobacter pylori infection by blocking the futalosine pathway, an alternative route for menaquinone (MK) biosynthesis.
Materials and Methods
1, Different H. pylori strains were grown in liquid media supplemented with linoleic acid, an omega-6 fatty acid, or its 10-hydroxy derivative, 10-hydroxy-cis-12-octadecenoic acid (HYA), in the presence or absence of MK. The bacterial numbers in the media were estimated by plating; 2, C57BL/6NCrl mice received drinking water supplemented with different fatty acids starting from 1 week before infection with H. pylori or Helicobacter suis until the end of the experiment. The gastric colonization levels of H. pylori or H. suis were determined 2 weeks after infection by plating or quantitative PCR, respectively; 3, Mice were given HYA, starting 1 week before infection with H. suis and continuing until 6 months after infection, for analysis of the gastric conditions.
Results
1, A low concentration (20 μmol/L) of HYA in culture broth suppressed the growth of H. pylori, and this inhibition was reduced by MK supplementation; 2, HYA treatment protected mice against H. pylori or H. suis infection; 3, HYA treatment suppressed the formation of lymphoid follicles in the gastric mucus layer after H. suis infection.
Conclusions
HYA prevents gastric Helicobacter infections by blocking their futalosine pathways. Daily HYA supplementation is effective for the prevention of gastric mucosa-associated lymphoid tissue lymphoma induced by persistent infection with H. suis.
http://ift.tt/2ipOjVS
Efficacy of three-in-one capsule bismuth quadruple therapy for Helicobacter pylori eradication in clinical practice in a multinational patient population
Abstract
Background
Bismuth quadruple therapy (BQT) has been proven superior to standard triple therapy for Helicobacter pylori eradication in randomized clinical trials; however, little is known about the efficacy of BQT in daily routine practice.
Methods
In a single-center cohort study, we analyzed consecutive H. pylori-positive patients in whom three-in-one capsule BQT (Pylera® + omeprazole) has been prescribed. All patients were instructed in a standardized fashion, and a prospective follow-up was planned. PCR on gastric biospies for clarithromycin and levofloxacin resistance was performed before treatment in a subgroup of patients. Treatment outcome was assessed by 13C urea breath test or by histology not earlier than 4 weeks after end of treatment.
Results
Three-in-one capsule BQT has been prescribed in 322 patients. Approximately 70.2% of patients had a migrational background. PCR results were available in 163 patients and identified resistance to clarithromycin and levofloxacin in 29 (17.8%) and 20 (12.3%) of cases, respectively. BQT was prescribed as first-line, second-line, and salvage treatments in 74%, 17%, and 9% of cases, respectively. Five patients discontinued treatment due to side effects (1.8%). By modified intention-to-treat and per-protocol analyzes, the overall H. pylori eradication rates were 95.0% (95% CI 94.92%-95.08%) and 96.7% (95% CI 94.6%-98.8%), respectively. The low number of treatment failures (n = 9) did not allow to identify risk factors for failure.
Conclusion
Three-in-one capsule bismuth quadruple therapy is effective and safe for treatment of H. pylori infection in routine practice, irrespective of the patient's migrational background or the number of previous treatment failures.
http://ift.tt/2g3mJwE
Protective efficacy of a hydroxy fatty acid against gastric Helicobacter infections
Abstract
Background
We have previously revealed that omega-3 polyunsaturated fatty acids can prevent Helicobacter pylori infection by blocking the futalosine pathway, an alternative route for menaquinone (MK) biosynthesis.
Materials and Methods
1, Different H. pylori strains were grown in liquid media supplemented with linoleic acid, an omega-6 fatty acid, or its 10-hydroxy derivative, 10-hydroxy-cis-12-octadecenoic acid (HYA), in the presence or absence of MK. The bacterial numbers in the media were estimated by plating; 2, C57BL/6NCrl mice received drinking water supplemented with different fatty acids starting from 1 week before infection with H. pylori or Helicobacter suis until the end of the experiment. The gastric colonization levels of H. pylori or H. suis were determined 2 weeks after infection by plating or quantitative PCR, respectively; 3, Mice were given HYA, starting 1 week before infection with H. suis and continuing until 6 months after infection, for analysis of the gastric conditions.
Results
1, A low concentration (20 μmol/L) of HYA in culture broth suppressed the growth of H. pylori, and this inhibition was reduced by MK supplementation; 2, HYA treatment protected mice against H. pylori or H. suis infection; 3, HYA treatment suppressed the formation of lymphoid follicles in the gastric mucus layer after H. suis infection.
Conclusions
HYA prevents gastric Helicobacter infections by blocking their futalosine pathways. Daily HYA supplementation is effective for the prevention of gastric mucosa-associated lymphoid tissue lymphoma induced by persistent infection with H. suis.
http://ift.tt/2ipOjVS
Efficacy of three-in-one capsule bismuth quadruple therapy for Helicobacter pylori eradication in clinical practice in a multinational patient population
Abstract
Background
Bismuth quadruple therapy (BQT) has been proven superior to standard triple therapy for Helicobacter pylori eradication in randomized clinical trials; however, little is known about the efficacy of BQT in daily routine practice.
Methods
In a single-center cohort study, we analyzed consecutive H. pylori-positive patients in whom three-in-one capsule BQT (Pylera® + omeprazole) has been prescribed. All patients were instructed in a standardized fashion, and a prospective follow-up was planned. PCR on gastric biospies for clarithromycin and levofloxacin resistance was performed before treatment in a subgroup of patients. Treatment outcome was assessed by 13C urea breath test or by histology not earlier than 4 weeks after end of treatment.
Results
Three-in-one capsule BQT has been prescribed in 322 patients. Approximately 70.2% of patients had a migrational background. PCR results were available in 163 patients and identified resistance to clarithromycin and levofloxacin in 29 (17.8%) and 20 (12.3%) of cases, respectively. BQT was prescribed as first-line, second-line, and salvage treatments in 74%, 17%, and 9% of cases, respectively. Five patients discontinued treatment due to side effects (1.8%). By modified intention-to-treat and per-protocol analyzes, the overall H. pylori eradication rates were 95.0% (95% CI 94.92%-95.08%) and 96.7% (95% CI 94.6%-98.8%), respectively. The low number of treatment failures (n = 9) did not allow to identify risk factors for failure.
Conclusion
Three-in-one capsule bismuth quadruple therapy is effective and safe for treatment of H. pylori infection in routine practice, irrespective of the patient's migrational background or the number of previous treatment failures.
http://ift.tt/2g3mJwE
Characterizing the Age and Stimulus Frequency Interaction for Ocular Vestibular-Evoked Myogenic Potentials.
Objectives: The normal process of aging is mostly associated with global decline in almost all sensory aspects of the human body. While aging affects the 500-Hz tone burst-evoked ocular vestibular-evoked myogenic potentials (oVEMPs) by reducing the amplitudes and prolonging the latencies, its interaction with oVEMP responses at other frequencies has not been studied. Therefore, the present study aimed at investigating the impact of advancing age on the frequency tuning of oVEMP. Design: Using a cross-sectional research design, oVEMPs were recorded for tone burst frequencies of 250, 500, 750, 1000, 1500, and 2000 Hz from 270 healthy individuals divided into six age groups (10-20, 20-30, 30-40, 40-50, 50-60, and >60 years). Results: The results revealed significantly lower response rates and amplitudes in age groups above 50 years of age than all the other groups at nearly all the frequencies (p =1000 Hz in most of the individuals above 60 years of age (p =1000 Hz in older adults, especially above 60 years of age. Conclusions: The results of the study showed significantly higher prevalence of frequency tuning at 1000 Hz in older adults above 60 years of age. Because the shift in frequency tuning to >=1000 Hz is frequently used for identification of Meniere's disease, it is suggested that age-related correction be used for the diagnosis of Meniere's disease when using frequency tuning of oVEMP. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2vdbnJn
http://ift.tt/2vdbnJn
Role of illumination intensity in microcystin development using Microcystis aeruginosa as the model algae
Abstract
Microcystis aeruginosa (M. aeruginosa) is one of the most common genera of cyanobacteria in algal blooms. In the present work, the impact of the illumination intensity on the growth of M. aeruginosa has been studied and a grinding method for the extraction of intracellular microcystins (MCs) was developed. The variations of algal density, pH, total phosphorus (TP), and total nitrogen (TN) have been investigated during MCs' culturing period. Results showed that the extraction efficiency of MC-YR by the grinding method was 275% higher than the sonication method, and the extraction efficiencies of MC-RR and MC-LR by the grinding method were similar to the sonication method. The optimal illumination intensity for M. aeruginosa was found to be 19–38 μmol m−2 s−1 with suitable pH range of 7.5–10.5. Active release of extracellular MCs was not significantly observed when illumination intensities were ≤ 38 μmol m−2 s−1. Furthermore, the intracellular MC yields under different illumination intensities were found to be a relatively stable level. However, excess illumination intensity (≥ 47 μmol m−2 s−1) led to the lysis of algal cell and increased the concentrations of extracellular MCs, with MC-RR as the dominant compound. The calculated intracellular/extracellular MCs ratios for MC-RR, MC-LR, and MC-YR were 2.38 (N = 100, SD = 2.44), 2.68 (N = 64, SD = 3.48), and 1.25 (N = 30, SD = 1.64), respectively. Strong illumination intensity and cell lysis were found to be the two major factors influencing the release of extracellular MCs.
http://ift.tt/2vdn3vR
Differential Response Pattern of Oropharyngeal Pressure by Bolus and Dry Swallows
Abstract
The aim of this study was to determine if bolus and dry swallow showed similar pressure changes in the oropharynx using our newly developed device. A unique character of it includes that baropressure can be measured with the sensor being placed in the balloon and can assess the swallowing mechanics in terms of pressure changes in the oropharynx with less influences of direct contacts of boluses and oropharyngeal structures during swallow indirectly. Fifteen healthy subjects swallowed saliva (dry), 15 ml of water, 45 ml of water, and 15 ml of two different types of food in terms of viscosity (potage soup-type and mayonnaise-type foods). Suprahyoid muscle activity was recorded simultaneously. Three parameters, area under the curve (AUC), peak amplitude, and duration of pressure, were analyzed from each swallow. Almost all of the bolus swallowing events had biphasic baropressure responses consisting of an early phase and late phase (99%), whereas 90% of the saliva swallowing events had a single phase. AUC, peak, and duration displayed greater effects during the late phase than during the early phase. Baropressure of the early phase, but not of the late phase, significantly increased with increasing volume; however, small but significant viscosity effects on pressure were seen during both phases. Peak pressure of the late phase was preceded by maximum muscle activity, whereas that of the early phase was seen when muscle activity displayed a peak response. These findings indicated that our device with the ability to measure baropressure has the potential to provide additional parameter to assess the swallow physiology, and biphasic baropressure responses in the early and late phases could reflect functional aspects of the swallowing reflexes.
http://ift.tt/2vWYeac
Predictive Value of the New Zealand Secretion Scale (NZSS) for Pneumonia
Abstract
Accumulated pharyngo-laryngeal secretions have been associated with aspiration and pneumonia. While traditional secretion scales evaluate location and amount, the eight-point New Zealand Secretion Scale (NZSS) uniquely encompasses a responsiveness subcomponent. This prospective observational study investigated the predictive value of NZSS for aspiration and pneumonia. Consecutive inpatients (N:180) referred for flexible endoscopic evaluation of swallowing (FEES) were recruited (neurological 49%, critical care 31%, structural 15%, other 5% etiologies). Mean age was 63 years (range 18–95 years, S.D. 18). A standardized protocol was completed on 264 FEES (180 first FEES, 84 repeat FEES). Penetration-aspiration scale (PAS) (ICC = .89) and NZSS (ICC = .91) were independently scored by two raters. Aspiration of food and/or fluids occurred in 36% of FEES; 24% silently. Median NZSS was 3 (range 0–7); with silent aspiration of secretions in 33% of FEES. There was a significant correlation between NZSS and PAS (R = .37, p < .001). Incidence of pneumonia during admission was 46% and was significantly associated with PAS (p < .001), NZSS (p < .001), age (p < .001), and tracheostomy (p < .001). Of those who developed pneumonia, 33% had both high PAS (>5) and high NZSS (>4). Eleven percent of those who developed pneumonia had an elevated NZSS (>4) in the absence of aspiration (PAS < 6). This large study reports the significant relationship between accumulated secretions, airway responsiveness, and pneumonia. This comprehensive scale is a useful tool when carrying out endoscopic evaluation and has the potential to predict pneumonia in patients irrespective of their aspiration status.
http://ift.tt/2xbhXRQ
Cross-Cultural Adaptation and Validation of the SWAL-QoL Questionnaire in Greek
Abstract
The purpose of this study was to translate and adapt the 44-item SWAL-QoL into Greek and examine its internal consistency, test–retest reliability, external construct validity, and discriminant validity in order to provide a validated dysphagia-specific QoL instrument in the Greek language. The instrument was translated into Greek using the back translation to ensure linguistic validity and was culturally adapted resulting in the SWAL-QoL-GR. Two groups of participants were included: a patient group of 86 adults (48 males; age range: 18–87 years) diagnosed with oropharyngeal dysphagia, and an age-matched healthy control group (39 adults; 19 males; age range: 18–84 years). The Greek 30-item version of the WHOQOL-BREF was used for assessment of construct validity. Overall, the questionnaire achieved good to excellent psychometric values. Internal consistency of all 10 subscales and the physical symptoms scale of the SWAL-QoL-GR assessed by Cronbach's α was good to excellent (0.811 < α < 0.940). Test–retest validity was found to be good to excellent as well. In addition, moderate to strong correlations were found between seven of the ten subscales of the SWAL-QoL-GR with limited items of the WHOQΟL-BREF (0.401 < ρ < 0.65), supporting good construct validity of the SWAL-QoL-GR. The SWAL-QoL-GR also correctly differentiated between patients with dysphagia and age-matched healthy controls (p < 0.001) on all 11 scales, further indicating excellent discriminant validity. Finally, no significant differences were found between the two sexes. This cultural adaptation and validation allows the use of this tool in Greece, further enhancing our clinical and scientific efforts to increase the evidence-based practice resources for dysphagia rehabilitation in Greece.
http://ift.tt/2vXeg3N
Pioneering Review Compares State-Level Hearing Aid Coverage
Researchers at the University of South Florida conducted the first-ever comprehensive review of state Medicaid hearing aid coverage for older adults. The study was published in the August edition of Health Affairs entitled "Medicaid Hearing Aid Coverage for Older Adult Beneficiaries: A State-by-State Comparison."
While more than 26 million older adults in the United States have hearing loss, only about 25 percent of those with moderate to severe hearing loss use hearing aids, and the percentage may be even lower in those with mild to moderate hearing loss. The study's lead author, Michelle Arnold, AuD, highlighted the significance of the issue: "Lack of hearing aid uptake is a public health concern, as untreated age-related hearing loss, with its concomitant reductions in speech understanding is associated with increased risks of social isolation, falls, hospitalizations and cognitive decline and with a disease burden of up to four disability-adjusted life years."
The researchers found that 22 states do not provide Medicaid hearing aid coverage at all since coverage is not federally mandated. Of the states that do provide coverage, the extent varies widely.
The study used six criteria to rank the states' Medicaid coverage policies, including eligibility of assessment and treatment, two hearing aids, batteries, supplies, follow-up rehabilitation, and repairs or replacement.
The researchers conclude the study by urging that "federal policy makers should consider making hearing health care, including the coverage of hearing aids, mandated under Medicaid."
Published: 8/22/2017 3:59:00 PM
http://ift.tt/2vWUDc5
Early Intervention Improves Vocabulary of Hearing- Impaired Children
A recent study conducted at the Institute of Cognitive Science (ICS) at the University of Colorado found that infants born with hearing loss who are identified and treated according to the Early Hearing Detection and Intervention (EHDI) guidelines have markedly better vocabulary outcomes than those who are not. This is the first multi-state study to examine the effectiveness of all three stages of EHDI on vocabulary outcomes.
The study analyzed 448 children (between the ages of 8 to 39 months) with hearing loss participating in the National Early Childhood Assessment Project in 12 states. Fifty-eight percent of the study participants were found to meet the EHDI 1-3-6 guidelines.
The EHDI 1-3-6 guidelines include a hearing loss screening within one month of age, a diagnosis of hearing loss by a specialist within three months of age, and an intervention by six months.
Of the participants who were treated within six months, their Vocabulary Quotients (VQs) had a mean of 82, while 64 percent of those who did not meet EHDI guidelines but had no additional disabilities had a score less than 75 (100 is the norm).
According to Christine Yoshinaga-Itano, PhD, audiologist and researcher at ICS, children who do not receive early intervention in accordance with the EHDI timeframe are considered to have what amounts to an "environmentally induced and preventable secondary disability" and observed to function like children with cognitive delay.
The researchers concluded that future systemic improvement of vocabulary learning will need to focus on "preventing widening delays with chronological age, assisting mothers with lower levels of education, and incorporating adults who are deaf/hard of hearing in the intervention process."
Published: 8/22/2017 8:28:00 AM
http://ift.tt/2xb40Ud
Local allergic rhinitis is an independent rhinitis phenotype: The results of a 10-years follow-up study
Abstract
Background
The knowledge about the natural history of local allergic rhinitis (LAR) is limited. One unmeet question is to demonstrate whether LAR should be considered the first step in the development of allergic rhinitis (AR) or an independent phenotype. The aim of this study was to prospectively evaluate the natural history of a population with LAR, the potential conversion to AR with systemic atopy, and the development of asthma during 10 years.
Methods
This is the second phase of a 10 year follow-up study of a cohort of 176 patients with LAR of recent onset and 115 age- and sex-matched healthy controls prospectively evaluated from 2005 to 2016. Clinical-demographic questionnaire, spirometry, skin prick-test, and specific-IgE were evaluated yearly. Nasal allergen provocation tests (NAPT) with D. pteronyssinus, Alternaria alternata, Olea europaea, and grass pollen were performed at baseline, and after 5 and 10 years.
Results
After 10 years LAR patients experienced a significant and clinically relevant worsening of the rhinitis, with increase of emergency assistance, development of asthma, loss of allergen tolerance, and impairment of the quality of life. This worsening became significant after 5 years and progressed throughout 10 years.
A similar rate of development of AR with systemic atopy was detected in patients and controls (9.7% vs 7.8%, Log-rank p=0.623). In 5 patients conversion to systemic atopy occurred >10 years (3%).
Conclusions
LAR is a well-differentiated clinical entity with a low rate of development of systemic atopy, a natural evolution towards worsening and a risk factor for suffering asthma.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wwExaS
Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis
Abstract
The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.
http://ift.tt/2vcNqSw
Rebirth of the Incretin Concept; its conception and early development
Source:Peptides
Author(s): Vincent Marks
This paper describes the resurrection of the Incretin Concept in the early 1960s. It began with the more or less simultaneous discovery by three groups working independently in London. Dupre demonstrated that secretin given intravenously with glucose increased its rate of disappearance from the blood, McIntyre and co-workers established that hyperglycaemia evoked by oral glucose stimulated more insulin secretion than comparable hyperglycaemia produced by intravenous glucose and Marks and Samols established the insulinotropic properties of glucagon. The concept evolved with the discovery by Samols and co-workers that oral glucose stimulated the release of immunoreactive glucagon-like substances from the gut mucosa and the subsequent isolation of glucagon immunoreactive compounds, most notably oxyntomodulin and glicentin, and of gastic inhibitory polypetide (GIP). It concluded with the isolation and characterisation of glucagon-like peptide 1 (7-36) amide.
http://ift.tt/2w1qwyE
Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Alerie Guzman De La Fuente, Simona Lange, Maria Elena Silva, Ginez A. Gonzalez, Herbert Tempfer, Peter van Wijngaarden, Chao Zhao, Ludovica Di Canio, Andrea Trost, Lara Bieler, Pia Zaunmair, Peter Rotheneichner, Anna O'Sullivan, Sebastien Couillard-Despres, Oihana Errea, Maarja A. Mäe, Johanna Andrae, Liqun He, Annika Keller, Luis F. Bátiz, Christer Betsholtz, Ludwig Aigner, Robin J.M. Franklin, Francisco J. Rivera
The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.
Graphical abstract
Teaser
Following toxin-induced demyelination in PC-deficient mice and using a number of in vitro approaches, Guzman de la Fuente et al. show that CNS pericytes (PCs) respond to demyelination and, through Lama2 secretion, stimulate oligodendrocyte progenitor cell differentiation during remyelination. These findings extend PC function beyond vascular homeostasis toward regeneration.http://ift.tt/2w1iYfu
Dopamine Encodes Retrospective Temporal Information in a Context-Independent Manner
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Kaitlyn M. Fonzi, Merridee J. Lefner, Paul E.M. Phillips, Matthew J. Wanat
The dopamine system responds to reward-predictive cues to reflect a prospective estimation of reward value, although its role in encoding retrospective reward-related information is unclear. We report that cue-evoked dopamine release in the nucleus accumbens core encodes the time elapsed since the previous reward or rather the wait time. Specifically, a cue that always follows the preceding reward with a short wait time elicits a greater dopamine response relative to a distinct cue that always follows the preceding reward with a long wait time. Differences in the dopamine response between short wait and long wait cues were evident even when these cues were never experienced together within the same context. Conditioned responding updated accordingly with a change in cue-evoked dopamine release but was unrelated to a difference in the dopamine response between cues. Collectively, these findings illustrate that the cue-evoked dopamine response conveys a subjective estimation of the relative reward rate.
Graphical abstract
Teaser
Fonzi et al. demonstrate that cue-evoked dopamine release encodes retrospective time-related information. They find that the dopamine system can discern differences between cues that have never been experienced together in the same context.http://ift.tt/2w1iXbq
The Proprioceptive System Regulates Morphologic Restoration of Fractured Bones
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Ronen Blecher, Sharon Krief, Tal Galili, Eran Assaraf, Tomer Stern, Yoram Anekstein, Gabriel Agar, Elazar Zelzer
Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed "natural reduction." Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity.
Graphical abstract
Teaser
Blecher et al. report that natural reduction, the process whereby fractured bones are realigned, fails in mutant mice lacking functional proprioceptive circuitry. Surprisingly, natural reduction was more rapid and effective in 3-month-old mice than in newborns. These findings suggest a physiological role for proprioception in non-autonomous regulation of skeletal integrity.http://ift.tt/2w1iWEo
Constitutive Immune Activity Promotes Tumorigenesis in Drosophila Intestinal Progenitor Cells
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Kristina Petkau, Meghan Ferguson, Silvia Guntermann, Edan Foley
Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity disrupts expression of homeostatic regulators such as Notch pathway components and induces hyperplasia throughout the gut. Consistent with these observations, we found that persistent immune signals interfere with progenitor cell differentiation and exacerbate the formation of Notch-dependent intestinal tumors. These findings uncover a link between constitutive immune activity and tumorigenesis in intestinal stem cells.
Graphical abstract
Teaser
Petkau et al. show that persistent immune activity in gut progenitor cells promotes tumorigenesis in adult flies.http://ift.tt/2w1iW7m
Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Min Xia, Kun Chen, Xiao Yao, Yichi Xu, Jiaying Yao, Jun Yan, Zhen Shao, Gang Wang
DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases.
Graphical abstract
Teaser
Xia et al. find that MED23 controls Mitf expression by modulating its enhancer function, thus connecting DNA repair to pigmentation.http://ift.tt/2vWQIMl
Coronary Artery Formation Is Driven by Localized Expression of R-spondin3
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Fabio Da Silva, Ana Sofia Rocha, Fariba Jian Motamedi, Filippo Massa, Cem Basboga, Harris Morrison, Kay Dietrich Wagner, Andreas Schedl
Coronary arteries are essential to support the heart with oxygen, and coronary heart disease is one of the leading causes of death worldwide. The coronary arteries form at highly stereotyped locations and are derived from the primitive vascular plexus of the heart. How coronary arteries are remodeled and the signaling molecules that govern this process are poorly understood. Here, we have identified the Wnt-signaling modulator Rspo3 as a crucial regulator of coronary artery formation in the developing heart. Rspo3 is specifically expressed around the coronary stems at critical time points in their development. Temporal ablation of Rspo3 at E11.5 leads to decreased β-catenin signaling and a reduction in arterial-specific proliferation. As a result, the coronary stems are defective and the arterial tree does not form properly. These results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation.
Graphical abstract
Teaser
Coronary arteries supply the heart with blood, and coronary diseases are one of the leading causes of death worldwide. Da Silva et al. find that RSPO3 is specifically expressed around the developing stems of the left and right coronaries, where it promotes their formation by stimulating arterial-specific proliferation through Wnt/β-catenin signaling.http://ift.tt/2vWJAzN
Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Alba Torrents de la Peña, Jean-Philippe Julien, Steven W. de Taeye, Fernando Garces, Miklos Guttman, Gabriel Ozorowski, Laura K. Pritchard, Anna-Janina Behrens, Eden P. Go, Judith A. Burger, Edith E. Schermer, Kwinten Sliepen, Thomas J. Ketas, Pavel Pugach, Anila Yasmeen, Christopher A. Cottrell, Jonathan L. Torres, Charlotte D. Vavourakis, Marit J. van Gils, Celia LaBranche, David C. Montefiori, Heather Desaire, Max Crispin, Per Johan Klasse, Kelly K. Lee, John P. Moore, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders
The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).
Graphical abstract
Teaser
Native-like HIV-1 envelope trimers are a platform for efforts to induce broadly neutralizing antibodies. Torrents de la Peña et al. design HIV-1 envelope trimers with enhanced stability and reduced flexibility. These modified trimers improve the induction of neutralizing antibodies and provide new opportunities toward elicitation of broadly neutralizing antibodies.http://ift.tt/2vX5NO3
PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Maria Gato-Cañas, Miren Zuazo, Hugo Arasanz, Maria Ibañez-Vea, Laura Lorenzo, Gonzalo Fernandez-Hinojal, Ruth Vera, Cristian Smerdou, Eva Martisova, Imanol Arozarena, Claudia Wellbrock, Diana Llopiz, Marta Ruiz, Pablo Sarobe, Karine Breckpot, Grazyna Kochan, David Escors
PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway. Moreover, somatic mutations found in human carcinomas within these PDL1 sequence motifs disrupted motif regulation, resulting in PDL1 molecules with enhanced protective activities from type I and type II IFN cytotoxicity. Overall, our results reveal a mode of action of PDL1 in cancer cells as a first line of defense against IFN cytotoxicity.
Graphical abstract
Teaser
Gato-Cañas et al. find that PDL1 protects cancer cells from interferon toxicity by counteracting interferon signaling through the activities of two non-classical conserved motifs. Human cancers acquire somatic mutations within these motifs that enhance PDL1 anti-interferon activities, favoring tumor progression.http://ift.tt/2vWnugz
Triggering of NOD2 Receptor Converts Inflammatory Ly6Chigh into Ly6Clow Monocytes with Patrolling Properties
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Anne-Julie Lessard, Manon LeBel, Benoit Egarnes, Paul Préfontaine, Peter Thériault, Arnaud Droit, Alexandre Brunet, Serge Rivest, Jean Gosselin
The signals that regulate the fate of circulating monocytes remain unknown. In the present study, we demonstrate that triggering of the NOD2 receptor by muramyl dipeptide (MDP) converts inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Administration of MDP to Nr4a1−/− mice, which lack Ly6Clow monocytes, or to Ly6Clow-depleted mice led to the emergence of blood-patrolling monocytes with a profile similar to that of Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Using intravital microscopy in animal models of inflammatory diseases, we also found that converted Ly6Chigh monocytes patrol the endothelium of blood vessels and that their presence contributes to a reduction in the inflammatory response following MDP injection. Our results demonstrate that NOD2 contributes to the regulation of blood monocytes and suggest that it could be therapeutically targeted to treat inflammatory diseases.
Graphical abstract
Teaser
The signals that regulate the conversion of inflammatory monocytes into patrolling subset(s) remain unknown. Here, Lessard et al. demonstrate that triggering NOD2 transforms inflammatory Ly6Chigh monocytes into Ly6Clow monocytes that look and function like patrolling cells.http://ift.tt/2vWFcAx
Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Zheng-Quan Tang, Laurence O. Trussell
Many studies have explored how neuromodulators affect synaptic function, yet little is known about how they modify computations at the microcircuit level. In the dorsal cochlear nucleus (DCN), a region that integrates auditory and multisensory inputs from two distinct pathways, serotonin (5-HT) enhances excitability of principal cells, predicting a generalized reduction in sensory thresholds. Surprisingly, we found that when looked at from the circuit level, 5-HT enhances signaling only from the multisensory input, while decreasing input from auditory fibers. This effect is only partially explained by an action on auditory nerve terminals. Rather, 5-HT biases processing for one input pathway by simultaneously enhancing excitability in the principal cell and in a pathway-specific feed-forward inhibitory interneuron. Thus, by acting on multiple targets, 5-HT orchestrates a fundamental shift in representation of convergent auditory and multisensory pathways, enhancing the potency of non-auditory signals in a classical auditory pathway.
Graphical abstract
Teaser
Neuromodulators may alter sensory processing upon changes in behavioral state. Tang and Trussell demonstrate that the neuromodulator serotonin shifts the representation of convergent auditory and multisensory pathways at a microcircuit level, enhancing the potency of non-auditory signals in a classical auditory brain region.http://ift.tt/2vWMHYp
Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Brian O. Orr, David Gorczyca, Meg A. Younger, Lily Y. Jan, Yuh-Nung Jan, Graeme W. Davis
The homeostatic control of presynaptic neurotransmitter release stabilizes information transfer at synaptic connections in the nervous system of organisms ranging from insect to human. Presynaptic homeostatic signaling centers upon the regulated membrane insertion of an amiloride-sensitive degenerin/epithelial sodium (Deg/ENaC) channel. Elucidating the subunit composition of this channel is an essential step toward defining the underlying mechanisms of presynaptic homeostatic plasticity (PHP). Here, we demonstrate that the ppk1 gene encodes an essential subunit of this Deg/ENaC channel, functioning in motoneurons for the rapid induction and maintenance of PHP. We provide genetic and biochemical evidence that PPK1 functions together with PPK11 and PPK16 as a presynaptic, hetero-trimeric Deg/ENaC channel. Finally, we highlight tight control of Deg/ENaC channel expression and activity, showing increased PPK1 protein expression during PHP and evidence for signaling mechanisms that fine tune the level of Deg/ENaC activity during PHP.
Graphical abstract
Teaser
Orr et al. define the subunit composition of an essential Deg/ENaC channel that controls the rapid induction and sustained expression of presynaptic homeostatic plasticity. The demonstration that PPK1 incorporates into DEG/ENaC channels with diverse physiological activities highlights the potential for tremendous DEG/ENaC channel diversity in Drosophila.http://ift.tt/2vX0BJZ
Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Oliver H. Miller, Andreas Bruns, Imen Ben Ammar, Thomas Mueggler, Benjamin J. Hall
The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT)→mPFC circuit that controls depression-like behavior.
Graphical abstract
Teaser
In these experiments, Miller et al. show that GluN2B-containing NMDARs are enriched at synapses between the medial dorsal thalamus and medial prefrontal cortex. They also show that post-developmental deletion of these receptors in the mPFC enhances synaptic connectivity and that direct activation of this circuit in vivo drives strong antidepressant-like behavior in mice.http://ift.tt/2vWlEwk
Neurotensin Receptor-1 Identifies a Subset of Ventral Tegmental Dopamine Neurons that Coordinates Energy Balance
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Hillary L. Woodworth, Hannah M. Batchelor, Bethany G. Beekly, Raluca Bugescu, Juliette A. Brown, Gizem Kurt, Patrick M. Fuller, Gina M. Leinninger
Dopamine (DA) neurons in the ventral tegmental area (VTA) are heterogeneous and differentially regulate ingestive and locomotor behaviors that affect energy balance. Identification of which VTA DA neurons mediate behaviors that limit weight gain has been hindered, however, by the lack of molecular markers to distinguish VTA DA populations. Here, we identified a specific subset of VTA DA neurons that express neurotensin receptor-1 (NtsR1) and preferentially comprise mesolimbic, but not mesocortical, DA neurons. Genetically targeted ablation of VTA NtsR1 neurons uncouples motivated feeding and physical activity, biasing behavior toward energy expenditure and protecting mice from age-related and diet-induced weight gain. VTA NtsR1 neurons thus represent a molecularly defined subset of DA neurons that are essential for the coordination of energy balance. Modulation of VTA NtsR1 neurons may therefore be useful to promote behaviors that prevent the development of obesity.
Graphical abstract
Teaser
Woodworth et al. identify a subset of VTA dopamine neurons that express neurotensin receptor-1. Ablation of these neurons leads to enhanced physical activity and energy expenditure that protect mice from diet-induced obesity, revealing an important role for VTA NtR1 neurons in the regulation of body weight.http://ift.tt/2vWPGQw
Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Mikkel Roland Holst, Maite Vidal-Quadras, Elin Larsson, Jie Song, Madlen Hubert, Jeanette Blomberg, Magnus Lundborg, Maréne Landström, Richard Lundmark
Cellular blebbing, caused by local alterations in cell-surface tension, has been shown to increase the invasiveness of cancer cells. However, the regulatory mechanisms balancing cell-surface dynamics and bleb formation remain elusive. Here, we show that an acute reduction in cell volume activates clathrin-independent endocytosis. Hence, a decrease in surface tension is buffered by the internalization of the plasma membrane (PM) lipid bilayer. Membrane invagination and endocytosis are driven by the tension-mediated recruitment of the membrane sculpting and GTPase-activating protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) to the PM. Disruption of this regulation by depleting cells of GRAF1 or mutating key phosphatidylinositol-interacting amino acids in the protein results in increased cellular blebbing and promotes the 3D motility of cancer cells. Our data support a role for clathrin-independent endocytic machinery in balancing membrane tension, which clarifies the previously reported role of GRAF1 as a tumor suppressor.
Graphical abstract
Teaser
Holst et al. show that clathrin-independent endocytosis facilitates the rearrangement of the cell surface in response to a decrease in cell volume. This regulation, mediated by the protein GRAF1, suppresses cellular blebbing and the invasiveness of cancer cells, clarifying why GRAF1 acts as a tumor suppressor.http://ift.tt/2vWKpby
Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Marco R. Cosenza, Anna Cazzola, Annik Rossberg, Nicole L. Schieber, Gleb Konotop, Elena Bausch, Alla Slynko, Tim Holland-Letz, Marc S. Raab, Taronish Dubash, Hanno Glimm, Sven Poppelreuther, Christel Herold-Mende, Yannick Schwab, Alwin Krämer
Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.
Graphical abstract
Teaser
Extra centrosomes are frequent in human cancers and cause chromosome missegregation via clustering into a pseudo-bipolar mitotic spindle array. Cosenza et al. now demonstrate that centriole rosettes, a transient stage of extra centrosome formation, drive chromosome missegregation in addition to centrosome clustering and are frequently found in primary tumors.http://ift.tt/2vWlzJ2
SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Waaqo Daddacha, Allyson E. Koyen, Amanda J. Bastien, PamelaSara E. Head, Vishal R. Dhere, Geraldine N. Nabeta, Erin C. Connolly, Erica Werner, Matthew Z. Madden, Michele B. Daly, Elizabeth V. Minten, Donna R. Whelan, Ashley J. Schlafstein, Hui Zhang, Roopesh Anand, Christine Doronio, Allison E. Withers, Caitlin Shepard, Ranjini K. Sundaram, Xingming Deng, William S. Dynan, Ya Wang, Ranjit S. Bindra, Petr Cejka, Eli Rothenberg, Paul W. Doetsch, Baek Kim, David S. Yu
DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.
Graphical abstract
Teaser
SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection and is dysregulated in Aicardi-Goutières syndrome and cancer. Daddacha et al. define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.http://ift.tt/2vWJtEn
Zscan4 Inhibits Maintenance DNA Methylation to Facilitate Telomere Elongation in Mouse Embryonic Stem Cells
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Jiameng Dan, Philippe Rousseau, Swanand Hardikar, Nicolas Veland, Jiemin Wong, Chantal Autexier, Taiping Chen
Proper telomere length is essential for embryonic stem cell (ESC) self-renewal and pluripotency. Mouse ESCs (mESCs) sporadically convert to a transient totipotent state similar to that of two-cell (2C) embryos to recover shortened telomeres. Zscan4, which exhibits a burst of expression in 2C-like mESCs, is required for telomere extension in these cells. However, the mechanism by which Zscan4 extends telomeres remains elusive. Here, we show that Zscan4 facilitates telomere elongation by inducing global DNA demethylation through downregulation of Uhrf1 and Dnmt1, major components of the maintenance DNA methylation machinery. Mechanistically, Zscan4 recruits Uhrf1 and Dnmt1 and promotes their degradation, which depends on the E3 ubiquitin ligase activity of Uhrf1. Blocking DNA demethylation prevents telomere elongation associated with Zscan4 expression, suggesting that DNA demethylation mediates the effect of Zscan4. Our results define a molecular pathway that contributes to the maintenance of telomere length homeostasis in mESCs.
Graphical abstract
Teaser
Mouse embryonic stem cells sporadically convert to a transient totipotent (2C-like) state in which shortened telomeres are extended dependent on Zscan4. Dan et al. demonstrate that Zscan4 facilitates telomere elongation by inducing Uhrf1-dependent Uhrf1 and Dnmt1 degradation, leading to global DNA demethylation.http://ift.tt/2vX3k66
Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Margot Martinez-Moreno, Timothy Mark O'Shea, John P. Zepecki, Alexander Olaru, Jennifer K. Ness, Robert Langer, Nikos Tapinos
Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS) biology.
Graphical abstract
Teaser
Martinez-Moreno et al. report a role for a long non-coding RNA antisense to the promoter of Egr2, Egr2-AS-RNA, during the response to peripheral nerve injury. Inhibition of Egr2-AS-RNA following sciatic nerve injury reverts EGR2-mediated gene expression and delays demyelination.http://ift.tt/2vWPD7i
Peptide-Based Scaffolds Support Human Cortical Progenitor Graft Integration to Reduce Atrophy and Promote Functional Repair in a Model of Stroke
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Fahad A. Somaa, Ting-Yi Wang, Jonathan C. Niclis, Kiara F. Bruggeman, Jessica A. Kauhausen, Haoyao Guo, Stuart McDougall, Richard J. Williams, David R. Nisbet, Lachlan H. Thompson, Clare L. Parish
Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form "bio-bridges" within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV), thereby mimicking the brain's major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair.
Graphical abstract
Teaser
Somaa et al. examine the capacity of peptide-based scaffolds to structurally and functionally support human pluripotent stem cell-derived neural transplants in the stroke-injured brain. Scaffolds promoted graft maturation and integration and reduced host tissue atrophy, resulting in improved motor function over a period of 9 months.http://ift.tt/2vXdIuY
Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics
Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Nigel G. Kooreman, Patricia E. de Almeida, Jonathan P. Stack, Raman V. Nelakanti, Sebastian Diecke, Ning-Yi Shao, Rutger-Jan Swijnenburg, Veronica Sanchez-Freire, Elena Matsa, Chun Liu, Andrew J. Connolly, Jaap F. Hamming, Paul H.A. Quax, Michael A. Brehm, Dale L. Greiner, Leonard D. Shultz, Joseph C. Wu
There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.
Graphical abstract
Teaser
Kooreman et al. use various types of humanized mice for the modeling of pluripotent stem cell alloimmunity. They report the development of a wasting disease-like syndrome within these mice over time, limiting their functionality, and provide ways to address this by using an immune reconstituted "allogenized" mouse model.http://ift.tt/2vWMBjv
Terminating the criminal collaboration in pancreatic cancer: Nanoparticle-based synergistic therapy for overcoming fibroblast-induced drug resistance
Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Liying Wang, Xiangrui Liu, Quan Zhou, Meihua Sui, Zipeng Lu, Zhuxian Zhou, Jianbin Tang, Yi Miao, Min Zheng, Weilin Wang, Youqing Shen
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a dismal overall prognosis mainly unchanged over the past decades. PDAC is generally refractory to conventional treatments, and thus novel therapies are urgently needed. Recently, accumulating evidence has indicated that human pancreatic stellate cells (PSCs) facilitate PDAC development and drug resistance through paracrine activation of hedgehog pathway. Here, we report that smart SN38 (active metabolite of irinotecan) polymeric prodrug-based nanoparticles effectively encapsulate the commercial hedgehog pathway inhibitor GDC-0449 for co-delivery. More intriguingly, we obtained size-tunable nanoparticles with increased GDC-0449 loading efficiency by simply extending the chain length of the hydrophobic SN38 block. To better evaluate the efficacy and investigate the synergistic mechanisms, we immortalized human PSCs and established fibroblast-containing models in vitro and in vivo. In PSCs, BxPC-3 cells and MIA PaCa-2 cells, GDC-0449 suppressed the co-culture induced up-regulations of the two drug resistance contributors: sonic hedgehog transcription factor glioma-associated protein1 (GLI-1) and UGT1A glucuronosyltransferase. Importantly, the nanoparticle-mediated co-delivery system exhibited potent antitumor efficacy with enhanced apoptosis and reduced collagen, α-SMA and GLI-1 expression in tumor tissues. These findings reveal a potential strategy to utilize nanoparticle-mediated drug co-delivery platform as an effective combination therapy for fibroblast-enriched PDAC.
http://ift.tt/2w11UWF
Utility of Tc-99m MDP bone SPECT in evaluation of osseous involvement in craniofacial malignancies
To assess the role of technetium-99m methoxy diphosphonate (Tc-99m MDP) single photon emission tomography (SPECT) imaging for the detection of osseous invasion in craniofacial malignancies.
http://ift.tt/2v3OFHt
Clinical study of splint therapeutic efficacy for the relief of temporomandibular joint discomfort
This study aimed to evaluate the relationship between displacement of the mandibular condyle/disc due to occlusal splint insertion with splint therapy and changes in discomfort of the temporomandibular joint (TMJ), and to clarify the relationships between the outcomes over time of temporomandibular discomfort and TMJ magnetic resonance imaging (MRI) findings at the initiation of splint therapy.
http://ift.tt/2v3R84R
Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Abstract
Background
Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry.
Methods
Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006–2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days.
Results
Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1–2 (OR 6.42 P < 0.0004 and OR 8.87, P < 0.0042), pre-operative transfusion of > 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008).
Conclusions
This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk.
http://ift.tt/2wlzcCv
Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort
Abstract
Background
Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry.
Methods
Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006–2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days.
Results
Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1–2 (OR 6.42 P < 0.0004 and OR 8.87, P < 0.0042), pre-operative transfusion of > 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008).
Conclusions
This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk.
http://ift.tt/2wlzcCv
Gender Perception After Raising Vowel Fundamental and Formant Frequencies: Considerations for Oral Resonance Research
Voice feminization therapy for male-to-female transgender women typically targets increasing fundamental frequency (F0). Increasing vowel formant frequencies (FFs) has also been proposed. To better understand formant conditions that shift listeners' perception of gender from male to "not-male," individual and combined vowel FFs were incrementally raised, whereas F0 was held constant at a gender-ambiguous level.
http://ift.tt/2vXjk8p
Convex Bone Deformity after Closed Reduction of Nasal Bone Fracture
Nasal fractures are the most common type of facial fracture treated by plastic surgeons. Here, we clarify the postoperative deformities that frequently remain after closed reduction of fresh nasal bone fracture by three-dimensional computed tomography (3D-CT).
http://ift.tt/2vcN2TR
Clinical Outcomes for Minimally Invasive Primary and Secondary Orbital Reconstruction using an Advanced Synergistic Combination of Navigation and Endoscopy
Sequelae of inadequate orbital reconstruction include enophthalmos, hypoglobus, and diplopia. Accuracy of orbital reconstruction is largely subjective and especially difficult to achieve due to anatomic distortion in secondary or late reconstruction and in extensive injury. We combined computer navigation and endoscopy to perform accurate, aesthetic, and safe minimal-access primary and secondary orbital reconstruction.
http://ift.tt/2wCP0k7
Sentinel lymph node biopsy for thin melanomas under the American Joint Committee on Cancer 8th edition cancer staging system
The American Joint Committee on Cancer (AJCC) will implement the 8th edition of their cancer staging system on the 1st January 2018, with changes to the way in which thin melanomas are classified. Our understanding of these criteria contrasts with previous correspondence in this journal.1 Tumours with a Breslow thickness <0.8mm will be classified as T1a if they do not exhibit ulceration, and as T1b if they do exhibit ulceration. All tumours measuring 0.8-1.0mm thick will be reclassified as T1b regardless of ulceration.
http://ift.tt/2vcZ8N5
Preventing the Complications of Tissue Expansion Using Fat Grafting Under Expanded Skin
We read with great interest the brief clinical report entitled "Preventing the complications of tissue expansion using fat grafting under expanded skin" by Jiang et al.1 The authors demonstrate for the first time a technique improving the texture of expanded skin and preventing expansion failure by lipofilling into the ischemic region of the expanded flap. We would like to congratulate the authors for their primary work to make the skin expansion can be smoothly completed. Improving expansion efficiency and decreasing complications of expansion are always the subjects that we have thought a great deal about and worked intensively on.
http://ift.tt/2wCmzTq
Motor Nerve to the Masseter: A Pediatric Anatomic Study and the “3:1 Rule”
The motor nerve to the masseter (masseteric nerve) provides a robust local neural source for facial reanimation and nerve transfer. Its intraoperative identification is well-described in adults. The purpose of this study was to determine the location of the motor nerve to the masseter in the pediatric population using surgical landmarks.
http://ift.tt/2vcQBti
Non-living microvascular training models: Face validity of liquid latex and the challenge of structural vs. “physiological” patency assessment
Microvascular anastomosis training increasingly uses assessment tools to objectively evaluate the surgeons' performance and to track progression in this challenging learning curve. The first steps in microvascular skills acquisition are accomplished via a variety of training models in a safe simulation training environment1, with an increasing use of non-living biological models over living animal models, in line with the ethical considerations of replacement, reduction and refinement.
http://ift.tt/2wlo2xO
Development of a Universal Nutritional Screening Platform for Plastic Surgery Patients
Background: Plastic surgeons routinely see patients with complex or chronic wounds of all etiology. In a previous study, we found that up to 1 in 4 of these patients is at risk for malnutrition, which may be influencing their ability to heal. The goal of this study was to develop and validate a universal screening protocol that would be fast and accurate and allow for effective intervention and optimization of nutrition before plastic surgery. Methods: To accomplish these goals, we adopted a 2-part screening algorithm using the Canadian Nutritional Screening Tool (CNST) to triage patients in our outpatient clinics and then further screened those identified as being at risk using the Subjective Global Assessment (SGA) tool and blood work. Results: We screened 111 patients with diagnoses related to breast cancer (n = 10; 9.01%), elective surgery (n = 38; 34.23%), emergency surgery (n = 8; 7.21%), fractures (n = 15; 13.51%), and wounds (n = 40; 36.04%). Of the screened subjects, 15.32% (n = 17) were found to be at nutritional risk using the CNST, and 13 were confirmed to be moderately or severely malnourished using the SGA. Importantly, there were no positive correlations between nutritional status and smoking, diabetes, body mass index, or age, indicating that a universal screening protocol is needed to effectively screen a diverse plastic surgery population for malnutrition. Conclusions: Screening patients with both the CNST and the SGA is an effective way to identify patients before surgery to improve outcomes.http://ift.tt/2g3LyJ0
Temporomandibular joint reconstruction after condylar fracture complication related to osteosynthesis material
Total condylar resorption and the failure of bone synthesis material as postoperative complications of condyle fracture are seldom reported in the literature. When these occur, they may severely limit temporomandibular joint (TMJ) function. In such cases, a reconstruction of the joint is indicated, which can be achieved by means of an alloplastic prosthesis. This article reports a rare case of impaction of osteosynthesis material in the region of the base of the skull associated with a mandibular condyle fracture treated with rigid internal fixation, which resulted in complications.
http://ift.tt/2g4kwkJ
Epinephrine use as a measure of successful food allergy management
In their recent article "Impact of school peanut-free policies on epinephrine administration," Bartnikas et al1 examine the effect of peanut-free policies on epinephrine administration in Massachusetts Public Schools, as a proxy for the effect of peanut-free policies on rates of allergic reactions.
http://ift.tt/2g2u5AR
Reply
We thank Ford et al1 for their correspondence and for raising the consideration that use of epinephrine autoinjectors may not be a reliable measure of food allergic reactions. As we acknowledged in the Discussion section of our article, "We used epinephrine administration as a proxy for anaphylaxis. However, allergic reactions can vary in severity and there may be heterogeneity in treatment."2
http://ift.tt/2ini5dQ
Changes in tonal audiometry in children with progressive sensorineural hearing loss and history of Neonatal Intensive Care Unit discharge. A 20 year long-term follow-up
Newborns from Neonatal intensive care units (NICU) are at high-risk for sensorineural hearing loss (SNHL) a follow-up is needed for early diagnosis and intervention. Our objective here was to describe the features and changes of SNHL at different periods during a follow-up of almost 20 years.
http://ift.tt/2xaQY9m
Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?
To update our knowledge regarding the effectiveness of voice therapy for the treatment of vocal disturbance associated with benign vocal fold lesions, including vocal polyps, nodules and cysts, and for determining the utility of voice therapy in treating organic voice disorders, while highlighting problems for the future development of this clinical field.
http://ift.tt/2vWvZs6
Risk factors for the occurrence of epistaxis: Prospective study
Analyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors.
http://ift.tt/2xamQKZ
A case of ectopic salivary gland of the larynx
A 46-year-old man presented with sore throat. Laryngoscopic findings revealed a smooth yellow mass occupying the anterior portion of the false vocal fold on the left side. The authors performed biopsy under general anesthesia. The histopathological diagnosis was ectopic salivary gland. Because salivary glands are usually not found under the false vocal fold mucosa, ectopic salivary gland of the larynx was diagnosed.It is necessary to consider the possibility of ectopic salivary gland for mass lesions if swelling of the provisional vocal cord is found.
http://ift.tt/2vWKmwL
Severe Ocular Myositis After Ipilimumab Treatment for Melanoma: A Report of 2 Cases
Ipilimumab binds and blocks cytotoxic T-lymphocyte-associated antigen-4, causing enhanced T-cell reaction, antitumor response, and significant improvement of the overall survival of patients with metastatic melanoma. Patients treated with ipilimumab can develop immune-related adverse effects, primarily dermatitis, colitis, hepatitis, and hypophysitis. Although, in phase I–III studies, 64.2% of all patients suffered from immune-related adverse effects, ocular adverse effects occurred in 1.3% only. In the cases reported below, 2 patients with metastatic melanoma developed severe ocular myositis after treatment with ipilimumab. These are the first 2 reports of successful treatment of this condition by use of a combination of methylprednisolone and mycophenolate mofetil, and, in 1 of the cases, additional medication with intravenous immunoglobulin.http://ift.tt/2wwtTk6
NK Cell–derived Exosomes From NK Cells Previously Exposed to Neuroblastoma Cells Augment the Antitumor Activity of Cytokine-activated NK Cells
Immune cell–derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells. Moreover, we have studied the NB-derived exosomes on NK cell function. The molecular load of the characterized exosomes (by means of nanoparticle-tracking analysis, flow cytometry, scanning electron microscopy, and western blot) from NK cells exposed to the NB cell revealed their expression of natural killer cell receptors in addition to CD56, NKG2D, and KIR2DL2 receptors. These exosomes were used to treat NK cells and thereafter administered to NB tumor cells both in vitro and in vivo. Our results showed some kind of NK cells' education by the exosomes. This education from NK cells previously exposed to NB cell–derived exosomes caused efficient and greater cytotoxicity against NB tumors, but NB-derived exosomes act as tumor promoters by providing a tumor supporting niche. Hence, this method of preparing the exosomes has a dramatic effect on activation of anti-NK cells against NB cells.http://ift.tt/2wwDsjh
Ex Vivo Induction of Multiple Myeloma-specific Immune Responses by Monocyte-derived Dendritic Cells Following Stimulation by Whole-tumor Antigen of Autologous Myeloma Cells
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo–generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation. Twenty patients with MM were enrolled in the study. Following stimulation and maturation, moDCs were tested for their capacity to induce T-helper 1 and cytotoxic T lymphocyte responses in vitro. Both strategies were effective in the induction of myeloma-specific cytotoxic T lymphocyte and T-helper 1 cells, as demonstrated by cytotoxicity and ELISpot assays. On the whole, T-cell responses were observed in 18 cases by either method of DC pulsing. We conclude that both whole-tumor antigen approaches are efficient in priming autologous antimyeloma T-cell responses and warrant further study aiming at the development of individualized DC vaccines for MM patients.http://ift.tt/2wwmKAo
Immune Checkpoint Inhibitors in Organ Transplant Patients
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. Excluding these patients was deliberate due to concern that immune checkpoint inhibitor therapy could lead to graft rejection. The PD-1 and CTLA-4 pathways are essential to downregulate our immune system in the setting of T-cell activation to prevent autoimmunity. Furthermore, both pathways are implicated in transplanted organ tolerance and modulation of the pathways may inadvertently lead to peripheral transplant rejection. Currently, there are no guidelines for the treatment of patients with immune checkpoint inhibitors in the setting of a prior organ transplant. Thus far, there are only 10 reported cases of patients in the literature who were treated in this setting. Two additional cases are reported herein, including 1 patient with a prior cardiac transplant receiving nivolumab for non–small cell lung cancer. Of the 12 cases, 4 patients experienced organ rejection. From these observations, the authors hypothesize factors that affect safety and of this treatment modality in this patient population. These factors include the integral role of the PD-1 pathway compared with the CTLA-4 pathway in organ acceptance, sequential implementation of different immune checkpoint inhibitor classes, length of time with a transplant before therapy, strength of immunosuppressive agents to prevent organ transplant rejection, and immunogenicity of the particular organ grafted. Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation.http://ift.tt/2wwz6bH
Immune-related Neurological Symptoms in an Adolescent Patient Receiving the Checkpoint Inhibitor Nivolumab
Immune checkpoint inhibitors are a novel group of immunotherapeutic agents for the treatment of cancer. Immune-related adverse events, including neurological symptoms, have been associated with these agents. We present the case of an adolescent with refractory Hodgkin lymphoma treated with nivolumab, a PD1 inhibitor, who developed Hashimoto thyroiditis, posterior reversible encephalopathy syndrome causing seizures, as well as urinary retention, truncal/appendicular spasticity, dysphagia, and a progressive encephalopathy that was clinically consistent with a diagnosis of progressive encephalopathy with rigidity and myoclonus, a stiff-person-syndrome spectrum disorder. He showed response and ultimately full recovery to a combination of intravenous steroids, intravenous immunoglobulin, and plasma exchange. To our knowledge, this is the first documented report of an immune-related neurological reaction to nivolumab in an adolescent patient and expands the spectrum of known nivolumab-associated toxicities.
http://ift.tt/2wwgCs4
http://ift.tt/2wwgCs4
Is voice therapy effective for the treatment of dysphonic patients with benign vocal fold lesions?
To update our knowledge regarding the effectiveness of voice therapy for the treatment of vocal disturbance associated with benign vocal fold lesions, including vocal polyps, nodules and cysts, and for determining the utility of voice therapy in treating organic voice disorders, while highlighting problems for the future development of this clinical field.
http://ift.tt/2vWvZs6
Risk factors for the occurrence of epistaxis: Prospective study
Analyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors.
http://ift.tt/2xamQKZ
A case of ectopic salivary gland of the larynx
A 46-year-old man presented with sore throat. Laryngoscopic findings revealed a smooth yellow mass occupying the anterior portion of the false vocal fold on the left side. The authors performed biopsy under general anesthesia. The histopathological diagnosis was ectopic salivary gland. Because salivary glands are usually not found under the false vocal fold mucosa, ectopic salivary gland of the larynx was diagnosed.It is necessary to consider the possibility of ectopic salivary gland for mass lesions if swelling of the provisional vocal cord is found.
http://ift.tt/2vWKmwL
Re: Re: Mandibular Wing Osteotomy: technical modification
We thank Dr Brusco for his interest in our recent paper and for his valuable comments on the use of 3-dimensional printed cutting guides for use with the chin wing technique of osteotomy. His concerns are well-founded, but while we also wish to gain the best aesthetic result, we think that the introduction of new techniques to minimise the risk of permanent damage to the inferior alveolar nerve should not be avoided, particularly at a tertiary centre that trains residents as one of its main purposes.
http://ift.tt/2vcQNso
Re: Mandibular wing osteotomy: technical modification
My compliments to Coopman et al on their recent paper.1 I am familiar with the "chin wing" and its technical issues because I worked with Albino Triaca in the Klinik Pyramide in Zürich while it was being developed, and I wish to raise a point that is crucial for the success of the operation.
http://ift.tt/2wCfaDG
If trainers regularly validate trainees’ eLogbook records, they will spot a trainee who is not keeping theirs up-to-date
The months of June and July are the season of the Annual Review of Competence Progression. During the last few weeks we have both participated in two different processes of review, during which a trainee in Oral and Maxillofacial Surgery had entered NO procedures into the eLogbook during the previous six months.
http://ift.tt/2vcIrRE
Customised instrument to retract alveolar subperiosteal flap during the placement of dental implants: new technique
Retraction of subperiosteal flaps on the buccolingual aspect of the alveolar ridge is important for the proper insertion of dental implants. The width and height of alveolar bone should be felt clearly to prevent misdirection of the implant or penetration of bony walls.1 Recently the Thudichum nasal speculum was described for retraction during the procedure,1 and here we describe a self-retaining instrument that we designed to retract the alveolar subperiosteal flap.
http://ift.tt/2wCh8nD
A Call for Federal Regulation of Obstructive Sleep Apnea in Transportation Workers
In a continuing quest to achieve regulatory consistency for diagnosing and treating obstructive sleep apnea in transportation workers, several sleep dentists took their concerns to Capitol Hill.
Drs. Elliott Alpher, Neal Seltzer and Michael Baylin met with a legislative aide for Senator Chris Van Hollen. (D – MD). Dr. Alpher and Dr. Baylin are Maryland residents. The three expressed concerns over the recent federal decision to halt work on a rule that would have regulated the diagnosis and treatment of obstructive sleep apnea in truck drivers and railway workers. Two weeks ago, the Federal Motor Carrier Safety Administration (FMCSA) and the Federal Railway Administration (FRA) discontinued the plan to establish a federal regulation. Instead the two agencies said that companies could develop their own standards.
The goal of the meeting with Senator Van Hollen's legislative aide for health issues was to ask the Senator to seek renewal of the formal regulatory rule-making. In addition, the doctors requested that a dental sleep medical practitioner be appointed to the FMCSA Medical Review Board, which establishes medical standards for transportation workers and sets training policy for certified medical examiners.
During the 45-minute session, the doctors explained that transportation workers endure long hours and irregular sleep patterns making them at higher risk of suffering from obstructive sleep disorders. They added that an estimated 18 million people suffer but are undiagnosed or treated.
"The health and well-being of truck drivers is critical to everyone on the highway," said Dr. Neal Seltzer of Long Island Smile.
"The lack of sleep and obstructive breathing are epidemics that will affect at least the next few generations," said Dr. Elliott Alpher.
"This lack affects your entire health and well-being," said Dr. Michael Baylin.
In a separate action, several senators called for Trump Administration to explain why it cancelled the rule-making. In a letter to the Department of Transportation on Monday, August 21, several senators asked for an explanation and all the documents that were used to cancel the rule-making process. The senators called on the Administration to reverse its decision.
"We strongly believe that DOT should immediately reconsider the decision to help avoid future fatigue-related tragedies."
The letter details several deadly railway crashes that were linked to undiagnosed sleep disorders. These included a 2013 Metro-North train derailment in New York and a New Jersey Transit crash last year. The letter is signed by Sens. Cory Booker (N.J.), Chuck Schumer (N.Y.), Bob Menendez (N.J.) and Kirsten Gillibrand (N.Y.).
For several years, The American Sleep and Breathing Academy has advocated for science-based diagnostic and treatment guidelines for the commercial trucking industry. In 2016, ASBA members submitted more than 1,000 pages of expert comments to a proposed federal rulemaking that would have established incomplete, confusing and inconsistent regulations for the diagnosis and treatment of obstructive sleep apnea.
Establishing consistent, science-based guidelines for the diagnosis and treatment of obstructive sleep apnea will improve the health of the workers and make the roads safer.
Current FMSCA Medical Review Board guidelines base a diagnosis upon three criteria, while the ASBA standard includes 14 scientific and medical points, including intraoral exams and measurements and allows for a home sleep study.
Further, the FMCSA guidelines require the driver to stop working, go to a sleep lab and return to work only conditionally until there is a diagnosis and treatment. This is costly, time-consuming and by the estimates of one trucking association, can cost the driver $5,000 to $7,000 each time.
FMCSA guidelines dictate that the continuous airway device, CPAP, is the preferred method of treatment. Patients are required to wear the CPAP for only four hours during their sleep periods. Dental sleep appliances are allowed only after the failure of CPAP therapy to improve the patient's breathing.
Pilot Sleep Program Needs Dental Sleep Expertise
In addition to the obstructive sleep apnea rule-making, the trio asked that a dental sleep medicine practitioner be allowed to help establish the proper protocol and data analysis methods for a proposed FMCSA pilot program called "Split Berth." It will examine whether allowing drivers to divide their current 14-hour work schedule and 10-hour consecutive sleep requirements into periods they manage would be beneficial. Currently the pilot program is under consideration.
While the split berth idea is favored by truck drivers, Drs. Alpher, Baylin and Seltzer expressed concerns that the pilot program is being established without the expertise of dental sleep medicine specialists.
http://ift.tt/2xasv3M
Effects of river-lake interactions in water and sediment on phosphorus in Dongting Lake, China
Abstract
As a large river connected lake, Dongting Lake is influenced by anthropogenic activities and the discharge from its upstream tributaries in the lake basin and by the water recharge via a connection to the Yangtze River (YR) outside the basin. This makes the lake phosphorous cycle more complex than that in other disconnected lakes. Here, we calculated section fluxes and ran a hydrodynamic model to investigate the phosphorus (P) variations in response to the changing interactions in the water and sediment between the YR, four tributaries, and the lake. Results show that particulate P was the dominant form with a significant linear relationship with suspended sediment (r 2 = 0.906). The sediment input reduction from the YR through three water inlets, which is closely related to the Three Gorges Reservoir operation since 2003, led to a decrease in the total P (TP) concentration in the western Dongting Lake. However, the impact and range of this decrease were fairly limited. Compared with the limited effect of the YR, the raised TP flux from the Yuanjiang tributary controlled the TP concentration at the outlet of the western Dongting Lake. Apart from the influence of the YR and the tributaries, anthropogenic activities (sand dredging) in the eastern Dongting Lake also contributed to a high TP concentration around the S10 area through sediment resuspension. We suggest that, compared with the reduction in TP flux and sediment load from the connected Yangtze River outside the basin, the elements within the basin (increased TP input from tributaries and sand dredging) have a greater effect on the variations of TP in Dongting Lake.
http://ift.tt/2vmrJhY
Εγγραφή σε:
Αναρτήσεις (Atom)