Are Anemia and Hypotension Causally Related to Perioperative Ischemic Optic Neuropathy?.

No abstract available

http://ift.tt/2hOAwV0

Long-term Results of 18 Fat Injections in Unilateral Vocal Fold Paralysis

The purposes of this study were to assess the long-term efficacy of medialization laryngoplasty via injection of autologous fat in patients with unilateral laryngeal paralysis, and to discuss the results based on the volume of fat injected and the size of the initial glottic gap.

http://ift.tt/2hUjXXm

Unilateral Vocal Fold Paralysis: A Systematic Review of Speech-Language Pathology Management

Dysphonia due to unilateral vocal fold paralysis (UVFP) can be characterized by hoarseness and weakness, resulting in a significant impact on patients' activity and participation. Voice therapy provided by a speech-language pathologist is designed to maximize vocal function and improve quality of life. The purpose of this paper is to systematically review literature surrounding the effectiveness of speech-language pathology intervention for the management of UVFP in adults.

http://ift.tt/2hPh10F

Continuous Peripheral Nerve Blocks: An Update of the Published Evidence and Comparison With Novel, Alternative Analgesic Modalities

A continuous peripheral nerve block (CPNB) consists of a percutaneously inserted catheter with its tip adjacent to a target nerve/plexus through which local anesthetic may be administered, providing a prolonged block that may be titrated to the desired effect. In the decades after its first report in 1946, a plethora of data relating to CPNB was published, much of which was examined in a 2011 Anesthesia & Analgesia article. The current update is an evidence-based review of the CPNB literature published in the interim. Novel insertion sites include the adductor canal, interpectoral, quadratus lumborum, lesser palatine, ulnar, superficial, and deep peroneal nerves. Noteworthy new indications include providing analgesia after traumatic rib/femur fracture, manipulation for adhesive capsulitis, and treating abdominal wall pain during pregnancy. The preponderance of recently published evidence suggests benefits nearly exclusively in favor of catheter insertion using ultrasound guidance compared with electrical stimulation, although little new data are available to help guide practitioners regarding the specifics of ultrasound-guided catheter insertion (eg, optimal needle–nerve orientation). After some previous suggestions that automated, repeated bolus doses could provide benefits over a basal infusion, there is a dearth of supporting data published in the past few years. An increasing number of disposable infusion pumps does now allow a similar ability to adjust basal rates, bolus volume, and lockout times compared with their electronic, programmable counterparts, and a promising area of research is communicating with and controlling pumps remotely via the Internet. Large, prospective studies now document the relatively few major complications during ambulatory CPNB, although randomized, controlled studies demonstrating an actual shortening of hospitalization duration are few. Recent evidence suggests that, compared with femoral infusion, adductor canal catheters both induce less quadriceps femoris weakness and improve mobilization/ambulation, although the relative analgesia afforded by each remains in dispute. Newly published data demonstrate that the incidence and/or severity of chronic, persistent postsurgical pain may, at times, be decreased with a short-term postoperative CPNB. Few new CPNB-related complications have been identified, although large, prospective trials provide additional data regarding the incidence of adverse events. Lastly, a number of novel, alternative analgesic modalities are under development/investigation. Four such techniques are described and contrasted with CPNB, including single-injection peripheral nerve blocks with newer adjuvants, liposome bupivacaine used in wound infiltration and peripheral nerve blocks, cryoanalgesia with cryoneurolysis, and percutaneous peripheral nerve stimulation.

http://ift.tt/2i1WbM9

From Contact to Contactless Pulse Oximetry: Can You Measure Me Now?

No abstract available

http://ift.tt/2hNswDG

Capturing Essential Information to Achieve Safe Interoperability

In this article, we describe the role of "clinical scenario" information to assure the safety of interoperable systems, as well as the system's ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore, improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheetsa and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a "patient-controlled analgesia safety interlock" are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a learning health system to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A Web-based research tool for implementing a means of acquiring and managing this information, the Clinical Scenario Repository™ (MD PnP Program), is described.

http://ift.tt/2hBM93j

Active and Passive Optical Imaging Modality for Unobtrusive Cardiorespiratory Monitoring and Facial Expression Assessment

Because of their obvious advantages, active and passive optoelectronic sensor concepts are being investigated by biomedical research groups worldwide, particularly their camera-based variants. Such methods work noninvasively and contactless, and they provide spatially resolved parameter detection. We present 2 techniques: the active photoplethysmography imaging (PPGI) method for detecting dermal blood perfusion dynamics and the passive infrared thermography imaging (IRTI) method for detecting skin temperature distribution. PPGI is an enhancement of classical pulse oximetry. Approved algorithms from pulse oximetry for the detection of heart rate, heart rate variability, blood pressure-dependent pulse wave velocity, pulse waveform-related stress/pain indicators, respiration rate, respiratory variability, and vasomotional activity can easily be adapted to PPGI. Although the IRTI method primarily records temperature distribution of the observed object, information on respiration rate and respiratory variability can also be derived by analyzing temperature change over time, for example, in the nasal region, or through respiratory movement. Combined with current research areas and novel biomedical engineering applications (eg, telemedicine, tele-emergency, and telemedical diagnostics), PPGI and IRTI may offer new data for diagnostic purposes, including assessment of peripheral arterial and venous oxygen saturation (as well as their differences). Moreover, facial expressions and stress and/or pain-related variables can be derived, for example, during anesthesia, in the recovery room/intensive care unit and during daily activities. The main advantages of both monitoring methods are unobtrusive data acquisition and the possibility to assess vital variables for different body regions. These methods supplement each other to enable long-term monitoring of physiological effects and of effects with special local characteristics. They also offer diagnostic advantages for intensive care patients and for high-risk patients in a homecare/outdoor setting. Selected applications have been validated at our laboratory using optical PPGI and IRTI techniques in a stand-alone or hybrid configuration. Additional research and validation is required before these preliminary results can be introduced for clinical applications.

http://ift.tt/2hBJAOM

Applying Computer Models to Realize Closed-Loop Neonatal Oxygen Therapy

BACKGROUND: Within the context of automating neonatal oxygen therapy, this article describes the transformation of an idea verified by a computer model into a device actuated by a computer model. Computer modeling of an entire neonatal oxygen therapy system can facilitate the development of closed-loop control algorithms by providing a verification platform and speeding up algorithm development. METHODS: In this article, we present a method of mathematically modeling the system's components: the oxygen transport within the patient, the oxygen blender, the controller, and the pulse oximeter. Furthermore, within the constraints of engineering a product, an idealized model of the neonatal oxygen transport component may be integrated effectively into the control algorithm of a device, referred to as the adaptive model. Manual and closed-loop oxygen therapy performance were defined in this article by 3 criteria in the following order of importance: percent duration of SpO2 spent in normoxemia (target SpO2 ± 2.5%), hypoxemia (less than normoxemia), and hyperoxemia (more than normoxemia); number of 60-second periods 95% SpO2; and number of manual adjustments. RESULTS: Results from a clinical evaluation that compared the performance of 3 closed-loop control algorithms (state machine, proportional-integral-differential, and adaptive model) with manual oxygen therapy on 7 low-birth-weight ventilated preterm babies, are presented. Compared with manual therapy, all closed-loop control algorithms significantly increased the patients' duration in normoxemia and reduced hyperoxemia (P

http://ift.tt/2hNu2Fy

The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems

Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account these systems' perspective. In this article, we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate standards development groups, some of which focus on safety and effectiveness and others focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development.

http://ift.tt/2hBEja4

Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients

Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (SpO2). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, SpO2 can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a SpO2/FIO2 diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real-time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency—mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals—and the analysis of arterial impedance, which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry.

http://ift.tt/2hBIVgn

Effect of Tapentadol on Splenic Cytokine Production in Mice.

BACKGROUND: Opioid drugs affect immunity, but not all opioid drugs share the same immunomodulatory properties. Tapentadol is an analgesic drug with a dual synergistic mechanism of action: [micro]-opioid receptor agonism and noradrenaline reuptake inhibition. Weaker [micro]-opioid receptor agonism combined with noradrenaline reuptake inhibition results in potent analgesia with reduced opioid side effects. We evaluated the impact of tapentadol on splenic cytokine in normal and in hyperalgesia/allodynia mice, comparing it with morphine and reboxetine, a noradrenaline reuptake inhibitor. METHODS: Tapentadol, reboxetine, and morphine were injected subcutaneously into naive and mice that underwent sciatic nerve chronic constriction injury, and their effect on splenic cytokines (interferon-[gamma] [IFN-[gamma]], interleukin [IL]-2, IL-10, and IL-4) was measured by enzyme-linked immunosorbent assay after acute or chronic treatment. Nociceptive thresholds, thermal hyperalgesia, and allodynia also were assessed. Data were analyzed with 2-way analysis of variance (behavior) or 1-way analysis of variance (cytokines) followed by Bonferroni post hoc test. RESULTS: Primary outcomes of our study were the effects of drugs on splenic cytokines. Our data indicate that acute tapentadol did not modify cytokine production in comparison with animals that received saline, whereas morphine suppressed all the cytokines: saline versus morphine 10 mg/kg (mean difference [MD], 95% confidence interval [CI]: IFN-[gamma] = 12,400 [7760, 17,040], P

http://ift.tt/2hUm9ht

Customized Minimally Invasive Orbital Decompression Surgery Improves Lower Eyelid Retraction and Contour in Thyroid Eye Disease.

Purpose: To investigate the outcome of a customized approach with targeted zygomatic basin bone removal orbital decompression in lower eyelid retraction and contour of patients with thyroid eye disease. Methods: In a comparative case series, clinical charts and photos of a consecutive sample of 92 patients with thyroid eye disease submitted to different types orbital decompression were studied. Exophthalmos, midpupil to lower eyelid margin distances (MRD2) at 11 meridians, and globe position were measured and compared according to the types of decompression. Each eyelid was also labeled as within or outside normal limits regarding both contour pattern analysis and MRD2 compared with a control normal range. Eyelid contour and globe position from patients with orbital decompression with zygomatic basin removal were compared with those without basin removal. Results: A total of 105 orbits from 57 patients met the study inclusion criteria. Ninety-eight orbits had lateral orbital wall decompression and in 53% of these cases, bone in the zygomatic basin was removed. Removal of the zygomatic basin did not significantly enhance decrease in proptosis, but significantly induced vertical globe descent and improved MRD2 (p

http://ift.tt/2h53ZuN

Outcomes of Endoscopic Dacryocystorhinostomy in Secondary Acquired Nasolacrimal Duct Obstruction: A Case-Control Study.

Introduction: Secondary acquired nasolacrimal duct obstruction (SANDO), where the obstruction is caused by a known process, is becoming more commonly treated by endoscopic dacryocystorhinostomy (endoDCR). This study evaluates outcomes of endoDCR for cases of SANDO in comparison to endoDCR outcomes treating primary acquired nasolacrimal duct obstruction (PANDO). Methods: All patients undergoing endoDCR from 2006 to 2015 at a tertiary referral center were reviewed for etiology of nasolacrimal duct obstruction (NLDO) and success of procedure. Inclusion criteria were preoperative determination of NLDO via probing and irrigation, greater than 60-day follow up with assessment of duct patency via probing and irrigation after silicone tube removal, and postoperative survey for recurrent epiphora. Exclusion criteria were cases treating partial NLDO, patients undergoing concurrent conjunctivodacryocystorhinostomy, and patients lost to follow up or with incomplete records. Preanalysis stratification was performed for the following preexisting conditions: PANDO, granulomatosis with polyangiitis, sarcoidosis, midfacial radiotherapy, radioactive iodine therapy, severe prolonged sinusitis, prior failed DCR, and midface trauma. The primary outcome was postoperative anatomical patency of the nasolacrimal system with resolution of epiphora. Fisher-Freeman-Halton exact tests were performed comparing each SANDO group to the PANDO group with statistical significance set at p

http://ift.tt/2i9TYdt

Evaluation of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Fellowship Program Website Content and Quality.

Purpose: The qualities that applicants value in the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellowship programs have been studied, but the availability of this information on program websites has not yet been reviewed. The authors evaluated the availability of resident-valued ASOPRS fellowship program information on the Internet. Methods: The authors performed an Internet search of the 53 ASOPRS fellowship program websites and evaluated websites for 20 characteristics of interest to ASOPRS fellowship applicants such as teaching faculty, program description, rotation schedule, operative cases, and interview information. Results: Of the 53 ASOPRS fellowship programs, 43 (81.1%) had a fellowship program-dedicated website. The fellowship websites contained a mean 7.6 characteristics (38.1%, range 0-15). Faculty listing, program description, and case diversity were the most commonly included data (74.4%, 72.1%, and 69.8%, respectively). Fellow selection process, interview information, and graduate job placement were least commonly included (7.0%, 2.3%, and 0.0%, respectively). There was no significant difference in website inclusiveness based on fellowship region or faculty number. Programs affiliated with an ophthalmology residency were more complete than those that were not (40.3% vs. 20.0%, p = 0.0098). Conclusions: This review found that most programs had websites and contained a reasonable number of characteristics. However, applicant-valued information regarding surgical volume, procedure variety, application information, and postgraduate employment history were often missing. American Society of Ophthalmic Plastic and Reconstructive Surgery fellowship programs may improve match outcomes by providing and enhancing program websites with details that their applicants seek. (C) 2016 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

http://ift.tt/2h57HES

Upper Eyelid Response to Topical 0.5% Apraclonidine.

Purpose: To describe the change in upper eyelid position in a self-reportedly normal population after the administration of topical 0.5% apraclonidine in each eye. Methods: One hundred self-reportedly normal subjects received a 1-time administration of topical 0.5% apraclonidine in each eye. Digital photographs were taken at baseline and then 30 and 45 minutes following apraclonidine instillation. Marginal reflex distance 1 was determined via image analysis of acquired digital photographs (image-derived measurements are given the prefix "i" in this study). The horizontal corneal diameter was used as a constant measurement scale in each photograph. Results: The mean increase in i-marginal reflex distance 1 post-administration of 0.5% apraclonidine was +0.70 +/- 0.60 mm (range, -0.94 to +2.66 mm) after 30 minutes and +0.68 +/- 0.59 mm (range, -0.69 to +2.54 mm) after 45 minutes. Of the 200 total eyelids in 100 subjects, 181 (90.5%) had an increase in i-marginal reflex distance 1 at 30 minutes. Of the 100 subjects, 85 (85%) had a bilateral increase in i-marginal reflex distance 1, 4 (4%) had a bilateral decrease, and 11 (11%) had a unilateral increase with a contralateral decrease. Conclusions: Given its predominant small-amplitude upper eyelid elevating effect, topical apraclonidine may be a useful off-label alternative treatment for mild upper eyelid ptosis and in eyelid asymmetry due to eyelid retraction through use in the contralateral eye. (C) 2016 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

http://ift.tt/2i9RImz

Influence of possible predictor variables on the outcome of primary oral squamous cell carcinoma: a retrospective study of 392 consecutive cases at a single centre

The successful treatment of oral squamous cell carcinoma (OSCC) depends on the treatment strategy. The prognosis is most often linked to the stage at initial presentation, but the effect of patient-related parameters on overall survival remains uncertain. In this study, 392 consecutive cases of OSCC seen between 2007 and 2013 at a single centre were analyzed retrospectively. Overall survival was assessed and univariate and multivariate Cox proportional hazards regression was used to identify associations between possible tumour-specific and patient-related variables and survival.

http://ift.tt/2hllFjK

Effects of Hypericum perforatum on the healing of xenografts: a histomorphometric study in rabbits

The aim of this study was to investigate effects of the Hypericum perforatum (St John's Wort) on bone healing in rabbit calvarium. Ten male New Zealand rabbits each had three bicortical defects made in the calvarial bones, which were filled with xenograft, xenograft+H perforatum oil extract, and autogenous graft. Four weeks postoperatively all rabbits were killed and the bony defects examined histomorphometrically. Tissue compartments including new bone (p<0.001), marrow space (p<0.001), and residual bone grafts (p=0.014) differed significantly among groups (p=0.00?).

http://ift.tt/2gWsUgY

Infant Oral Mutilation – a Child Protection Issue?

Background: Infant oral mutilation (IOM) is a traditional practice involving "gouing out" of infant healthy tooth buds using crude methods in non-sterile conditions. It is usually performed by village healers in low income countries as an accepted remedy for common childhood illness, potentially leading to dento-alveolar and systemic complications including death.

http://ift.tt/2i3WwxU

Open surgery of the TMJ – What are the real Indications?

Open joint TMJ surgery is undertaken for a variety of reasons, and not all of these are associated with positive outcomes.

http://ift.tt/2gWplaM

The effect of deprivation on the Incidence of Mandibular fractures in a British city

Aim: To examine the relationship between social and material deprivation and mandibular fractures.

http://ift.tt/2i3Zd2A

To biopsy or not to biopsy? That is the question...

Introduction: Non melanoma skin cancers (NMSC) are common cancers affecting nearly 100,000 people in the UK every year.

http://ift.tt/2gWpueh

Sentinel lymph node biopsy for head and neck melanoma - a multi-centre study examining efficacy and safety

Introduction: Sentinel lymph node biopsy (SLNB) is a highly accurate staging procedure for malignant melanoma (MM). The use of SLNB in head and neck melanoma has recently gained popularity as it is thought to offer useful prognostic information as upstaging of disease can allow patients to enter novel trial based targeted therapies.

http://ift.tt/2i3Ww0S

Urgent or Not? Analysis of referrals to Oral and Maxillofacial Surgery in NHS Lanarkshire in a 1 month period

Background: New patient referrals are largely from GPs and GDPs and at times are inappropriate in content or nature (marked urgent unnecessarily). Whilst vital some patients are seen urgently, others must be seen routinely for time management and fairness.

http://ift.tt/2gWsTJW

Sentinel node biopsy for primary salivary gland tumours; feasibility study of a new technique

Introduction/Aims: There is no consensus on management of the N0 neck in patients with primary salivary neoplasms. Lymphatic drainage of the salivary glands is not well understood and elective neck dissection may miss the at risk lymph nodes. Sentinel node biopsy (SNB) is an accurate staging tool in other solid tumours but has not been widely described in salivary gland disease. We show that lymphatic drainage from primary salivary malignancy can be accurately mapped using a combination of SPECT/CT and navigational surgery.

http://ift.tt/2gWnQJw

Do new NICE oral cancer referral guidelines (NG12) risk delay in cancer diagnosis? An audit comparing outcomes of the new guidelines against old guidelines

Introduction: The National Institute for Health and Care Excellence (NICE) publish referral guidance for two week wait (2WW) suspected cancer referrals (CG27 2005, NG12 2015). NG12 updated CG27 and now recommends certain presentations, if identified by a GP, should be referred to a dentist for assessment (criterion 1.8.4). We compared NG12 to CG27 in a cohort of patients referred to an Oral and Maxillofacial Surgery department to assess likely impact on outcomes.

http://ift.tt/2i3Pn0C

The use of a skin regeneration system for multiple intra-oral purposes

Objective: To trial the use of Integra© skin regeneration system intra-orally to avoid the necessity for mucosal flaps, free flaps or skin grafts

http://ift.tt/2gWodnz

Quality of Informed Consent Given to Surgical Skin Cancer Patients at Gloucester Royal Hospital

Background: The Oral and Maxillofacial Department at Gloucester Royal Hospital provides on average 500 surgical removals of skin cancer lesions per year.

http://ift.tt/2i3W1Uz

Injuries to the head and neck in Homer's Odyssey

The odyssey is one of the most famous and influential poems ever conceived and together with the Iliad are considered to be the most prominent and representative works of the ancient Greek epic poetry. Our purpose was to retrieve and systematically record the head and neck injuries mentioned in the Odyssey.

http://ift.tt/2gWprz7

A Clinical Audit on the Management of Oral Lichen Planus within the Oral and Maxillo-facial Department at the University Hospital of Manchester

Introduction: Lichen planus is an inflammatory, autoimmune mucocutaneous disease. Oral lichen planus (OLP) has a documented malignant transformation risk of 1-3%, therefore it is important that patients are followed up appropriately.

http://ift.tt/2i41n2f

Impact of malignant cerebral artery infarction guidelines on the profile of the cranioplasty service

Background: Early decompressive craniectomy (DC) for malignant middle cerebral artery (MCA) infarction leads to improved survival, as demonstrated by three multicenter randomized controlled trials (DECIMAL, DESTINY, HAMLET). The survivors of a malignant MCA stroke manifest complex medical and neurological problems along with extensive calvarial defects that require cranioplasty.

http://ift.tt/2gWrvXz

The Inclusion of Mandibular Condyles in Orthopantomogram radiographs for Trauma cases: a retrospective audit at a Regional Maxillofacial Unit

Aims: In this retrospective study, we aim to analyse Orthopantomogram (OPG) x-rays taken for mandibular fractures at a major trauma facility. This is to determine their overall diagnostic viability and particularly the inclusion of the mandibular condyles.

http://ift.tt/2i3SBRU

Unilateral and bilateral temporomandibular joint reconstruction in children using autogenous costochondral grafting: An outcome study of 60 patients over a 28-year period

Costochondral grafting (CCG) for temporomandibular joint (TMJ) reconstruction can be diversely used for both congenital and acquired TMJ absence or malfunction. Using a CCG gained increasing popularity in children due to its growth potential and autogenous origin. The disadvantages are its unpredictable growth pattern and ankylosis risks.

http://ift.tt/2gWeKfK

An audit to assess handover techniques at Sheffield Teaching Hospitals

Introduction: Effective clinical handover is paramount in a successful patient journey, ensuring excellence in health-care quality and safety. Studies have shown that poor handover can result in patient harm and this is no different for dental core trainees on the maxillofacial ward.

http://ift.tt/2i3ZS3W

Implant Rehabilitation of Hypodontia Patients: Surgical Considerations

Aims: To evaluate the surgical and clinical outcomes of hypodontia patients undergoing surgical management and implant rehabilitation between the Queen Elizabeth Hospital Birmingham (QEHB) and the Birmingham Dental Hospital (BDH)

http://ift.tt/2gWkQNc

Throat packs; are we compliant with NPSA guidelines?

The use of throat packs can be contentious with the decision undertaken by surgeon, anaesthetist or both. Blackburn and Knepil undertook a national BAOMS questionnaire on throat pack usage in 2008. Afterwards National Patient Safety Advice (NPSA) guidelines followed with no subsequent update. We report an audit of compliance with these in Hull Royal Infirmary.

http://ift.tt/2i3Ya2t

Early Alterations of Hippocampal Neuronal Firing Induced by Abeta42

We studied the effect of Amyloid β 1-42 oligomers (Abeta42) on Ca²⁺ dependent excitability profile of hippocampal neurons. Abeta42 is one of the Amyloid beta peptides produced by the proteolytic processing of the amyloid precursor protein and participates in the initiating event triggering the progressive dismantling of synapses and neuronal circuits. Our experiments on cultured hippocampal network reveal that Abeta42 increases intracellular Ca²⁺ concentration by 46% and inhibits firing discharge by 19%. More precisely, Abeta42 differently regulates ryanodine (RyRs), NMDA receptors (NMDARs), and voltage gated calcium channels (VGCCs) by increasing Ca²⁺ release through RyRs and inhibiting Ca²⁺ influx through NMDARs and VGCCs. The overall increased intracellular Ca²⁺ concentration causes stimulation of K⁺ current carried by big conductance Ca²⁺ activated potassium (BK) channels and hippocampal network firing inhibition. We conclude that Abeta42 alters neuronal function by means of at least 4 main targets: RyRs, NMDARs, VGCCs, and BK channels. The development of selective modulators of these channels may in turn be useful for developing effective therapies that could enhance the quality of life of AD patients during the early onset of the pathology.

http://ift.tt/2hUcpDT

Spatiotemporal Dynamics of Attention Networks Revealed by Representational Similarity Analysis of EEG and fMRI

The fronto-parietal attention networks have been extensively studied with functional magnetic resonance imaging (fMRI), but spatiotemporal dynamics of these networks are not well understood. We measured event-related potentials (ERPs) with electroencephalography (EEG) and collected fMRI data from identical experiments where participants performed visual and auditory discrimination tasks separately or simultaneously and with or without distractors. To overcome the low temporal resolution of fMRI, we used a novel ERP-based application of multivariate representational similarity analysis (RSA) to parse time-averaged fMRI pattern activity into distinct spatial maps that each corresponded, in representational structure, to a short temporal ERP segment. Discriminant analysis of ERP-fMRI correlations revealed 8 cortical networks—2 sensory, 3 attention, and 3 other—segregated by 4 orthogonal, temporally multifaceted and spatially distributed functions. We interpret these functions as 4 spatiotemporal components of attention: modality-dependent and stimulus-driven orienting, top-down control, mode transition, and response preparation, selection and execution.

http://ift.tt/2hPdG1D

Delta-Band Oscillations in Motor Regions Predict Hand Selection for Reaching

Current models hold that action selection is achieved by competitive interactions between co-existing motor representations associated with each potential action. Critically, selection via competition requires biasing signals to enable one of these alternatives to be selected. This study tested the hypothesis that selection is related to the prestimulus excitability of neuronal ensembles in which movements are encoded, as assessed through the phase of delta-band oscillations (2–4 Hz). Electroencephalography was recorded while participants performed speeded reaches toward appearing visual targets using the hand of their choice. The target locations were controlled such that only targets for which the left and right hands were selected equally often were used for analysis. Results revealed that hand selection as well as reach reaction times strongly depended upon the instantaneous phase of delta at the moment of target onset. This effect was maximal over contralateral motor regions, and occurred in the absence of prestimulus alpha- (8–12 Hz) and beta-band (15–30 Hz) amplitude modulations. These findings demonstrate that the excitability of motor regions acts as a modulatory factor for hand choice during reaching. They extend current models by showing that action selection is related to the underlying brain state independently of previously known decision variables.

http://ift.tt/2hUnWmK

Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development

Neuronal survival and morphological maturation depends on the action of the transcription factor calcium responsive element binding protein (CREB), which regulates expression of several target genes in an activity-dependent manner. However, it remains largely unknown whether CREB-mediated transcription could play a role at early stages of neuronal differentiation, prior to the establishment of functional synaptic contacts. Here, we show that CREB is phosphorylated at very early stages of neuronal differentiation in vivo and in vitro, even in the absence of depolarizing agents. Using genetic tools, we also show that inhibition of CREB-signaling affects neuronal growth and survival in vitro without affecting cell proliferation and neurogenesis. Expression of A-CREB or M-CREB, 2 dominant-negative inhibitors of CREB, decreases cell survival and the complexity of neuronal arborization. Similar changes are observed in neurons treated with protein kinase A (PKA) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitors, which also show decreased levels of pCREBSer133. Notably, expression of CREB-FY, a Tyr134Phe CREB mutant with a lower Km for phosphorylation, partly rescues the effects of PKA and CaMKII inhibition. Our data indicate that CREB-mediated signaling play important roles at early stages of cortical neuron differentiation, prior to the establishment of fully functional synaptic contacts.

http://ift.tt/2i9XSDu

Letter to the editor regarding cardiac arrest with vagal stimulation during intraoperative nerve monitoring

http://ift.tt/2hObViY

Reply to letter to the editor regarding cardiac arrest after vagal stimulation in intraoperative neuromonitoring

http://ift.tt/2hCjfjB

Letter to the editor regarding cardiac arrest with vagal stimulation during intraoperative nerve monitoring

http://ift.tt/2hObViY

Reply to letter to the editor regarding cardiac arrest after vagal stimulation in intraoperative neuromonitoring

http://ift.tt/2hCjfjB

Renal complications of immune checkpoint blockade

Publication date: Available online 19 December 2016
Source:Current Problems in Cancer
Author(s): Naoka Murakami, Shveta Motwani, Leonardo V. Riella
Immune checkpoint inhibitors have been approved for a variety of cancer species. Renal complications in use of these agents are not very common compared with other immune related adverse events (irAE). However, it is crucial for physicians to recognize and manage renal manifestations of irAE. In this review, we will summarize the up-to-date knowledge of the clinical presentation, pathological features and management of renal irAE. In addition, we will discuss the safety of immune checkpoint inhibitors in patients with chronic kidney disease as well as in kidney transplant recipients.



http://ift.tt/2hPbvey

Toxicity of concurrent stereotactic radiotherapy and targeted therapies or immunotherapy: a systematic review.

Publication date: Available online 19 December 2016
Source:Cancer Treatment Reviews
Author(s): Stephanie G.C. Kroeze, Corinna Fritz, Morten Hoyer, Simon S. Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
Background and PurposeBoth stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.Material and MethodsPubMed and EMBASE databases were searched for English literature published up to april 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK". Studies performing SRT during or within 30 days of targeted/immunotherapy, reporting severe (⩾Grade 3) toxicity were included.ResultsConcurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra-cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT.ConclusionsThis review gives a best-possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field.



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Reliability and minimal detectable change of transcranial magnetic stimulation outcomes in healthy adults: A systematic review

Publication date: Available online 19 December 2016
Source:Brain Stimulation
Author(s): Louis-David Beaulieu, Véronique H. Flamand, Hugo Massé-Alarie, Cyril Schneider
BackgroundTranscranial magnetic stimulation (TMS) is used worldwide for noninvasively testing human motor systems but its psychometric properties remain unclear.Objective/Hypothesis. This work systematically reviewed studies on the reliability of TMS outcome measures of primary motor cortex (M1) excitability in healthy humans, with an emphasis on retrieving minimal detectable changes (MDC).MethodsThe literature search was performed in three databases (Pubmed, CINAHL, Embase) up to June 2016 and additional studies were identified through hand-searching. French and English-written studies had to report the reliability of at least one TMS outcome of M1 in healthy humans. Two independent raters assessed the eligibility of potential studies, and eligible articles were reviewed using a structured data extraction form and two critical appraisal scales.ResultsA total of 34 articles met the selection criteria, which tested the intra- and inter-rater reliability (relative and absolute subtypes) of several TMS outcomes. However, our critical appraisal of studies raised concerns on applicability and generalization of results because of methodological and statistical pitfalls. Importantly, MDC were generally large and likely affected by various factors, especially time elapsed between sessions and number of stimuli delivered.ConclusionsThis systematic review underlined that the evidence about the reliability of TMS outcomes is scarce and affected by several methodological and statistical problems. Data and knowledge of the review provided however relevant insights on the ability of TMS outcomes to track plastic changes within an individual or within a group, and recommendations were made to level up the quality of future work in the field.



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The critical role of the dorsomedial frontal cortex in voluntary action inhibition: a TMS study

Publication date: Available online 19 December 2016
Source:Brain Stimulation
Author(s): Stefania C. Ficarella, Lorella Battelli
BackgroundAction inhibition is a complex decision process that can be triggered by external factors (exogenous) or internal decisions (endogenous). While the neuronal underpinnings of exogenous action inhibition have been extensively investigated, less is known about the brain areas responsible for endogenous action inhibition. Objective. We used inhibitory repetitive transcranial magnetic stimulation (rTMS) to test the causal role of two brain areas, the left dorsal Frontal Medial Cortex (dFMC) and the right Inferior Frontal Cortex (rIFC) in exogenous and endogenous action inhibition. Methods. The exogenous condition was a modified version of the Go/NoGo paradigm, where a green stimulus served as a cue to perform an action (a button press, Exogenous-Go), while a magenta stimulus indicated that action should be withheld (Exogenous-NoGo). Crucially, for the endogenous condition we psychophysically generated a shade of color that participants randomly categorized as green or magenta. This unique stimulus, randomly intermixed with green and magenta stimuli, forced participants to perform an endogenous (internally-driven) choice to either execute or inhibit the action. Results. In the endogenous condition, at baseline participants executed the action on half the trials; however, after 1-Hz rTMS over the dFMC they responded significantly more frequently, indicating a reduced response inhibition. The effect was selective for the dFMC stimulation and sustained in time. Moreover, no significant effects were found in the exogenous condition. Conclusions. These results support the causal role of the left dFMC in endogenous action inhibition and, more generally, the notion of separate brain circuits for endogenous and exogenous action inhibition.



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Graphene oxide destabilizes myoglobin and alters its conformation

Publication date: Available online 19 December 2016
Source:Carbon
Author(s): Zhaohua Zhu, Yanqing Wang, Yijun Kang, Hongmei Zhang, Zhengming Zhang, Zhenghao Fei, Jian Cao
In this work, a series of biophysical assays were performed in order to analyze the effects of a novel two-dimensional carbon nano-material graphene oxide (GO) on the conformational changes of myoglobin (Mb). This study, for the first time, reveals the molecular interactions of GO with Mb. The conformation of the protein is obviously affected due to the binding interaction of GO with Mb. GO has high ability in disturbing the secondary of Mb by forming the Mb-GO conjunction. Multi-noncovalent interactions including hydrophobic, hydrogen bonds, van der Waals interactions and electrostatic forces contribute to the formation of Mb-GO conjunction. Our findings also show that the existence of GO can obviously decrease the thermal stability of protein. In addition, molecular modeling was used to analyze the lowest energy binding mode of GO with Mb. Taken together, this work can provide an insight into the biological interaction GO-heme protein in some biological applications.

Graphical abstract

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Influences of O2 and O3 on the heterogeneous photochemical reaction of NO2 with humic acids

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Chong Han, Wangjin Yang, He Yang, Xiangxin Xue
Oxidizing components in the atmosphere may play competitive roles in the heterogeneous photochemical reaction of NO2 with humic acids (HA). Effects of O2 and O3 on the conversion of NO2 to HONO on HA under simulated sunlight were investigated using a flow tube reactor. The uptake coefficient (γ) of NO2 and the HONO formation rate decreased with the increase of the O2 content (0%–20%) and the O3 concentration (0–100 ppb). The HONO yield was observed to be independent of the O2 content, whereas it inversely depended on the O3 concentration. In addition, the aging process of HA by O2 and O3 under irradiation resulted in the decrease in the reactivity of HA toward NO2, as shown by lower γ and HONO formation rate, while it has little influence on the HONO yield. Finally, the mechanism of role of O2 and O3 in the photochemical reaction of NO2 with HA was discussed in detail.



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Genesis of the Zinkgruvan stratiform Zn-Pb-Ag deposit and associated dolomite-hosted Cu ore, Bergslagen, Sweden

Publication date: April 2017
Source:Ore Geology Reviews, Volume 82
Author(s): N.F. Jansson, A. Zetterqvist, R.L. Allen, K. Billström, L. Malmström
Zinkgruvan, a major stratiform Zn-Pb-Ag deposit in the Paleoproterozoic Bergslagen region, south-central Sweden, was overprinted by polyphase ductile deformation and high-grade metamorphism (including partial melting of the host succession) during the 1.9–1.8Ga Svecokarelian orogeny. This complex history of post-ore modification has made classification of the deposit difficult. General consensus exists on a syngenetic-exhalative origin, yet the deposit has been variably classified as a volcanogenic massive sulfide (VMS) deposit, a sediment-hosted Zn (SEDEX) deposit, and a Broken Hill-type (BHT) deposit. Since 2010, stratabound, cobaltiferous and nickeliferous Cu ore, comprising schlieren and impregnations of Cu, Co and Ni sulfide minerals in dolomitic marble, is mined from the stratigraphic footwall to the stratiform Zn-Pb-Ag ore. This ore type has not been fully integrated into any of the existing genetic models. Based on a combination of 1) widespread hematite-staining and oxidizing conditions (Fe2O3>FeO) in the stratigraphic footwall, 2) presence of graphite and reducing conditions (Fe2O3<FeO) in the ore horizon and hangingwall and 3) intense K-feldspar alteration and lack of feldspar-destructive alteration in the stratigraphic footwall, we suggest that both the stratiform Zn-Pb-Ag and the dolomite-hosted Cu ore can be attributed to the ascent and discharge of an oxidized, saline brine at near neutral pH. Interaction of this brine with organic matter below the seafloor, especially within limestone, formed stratabound, disseminated Cu ore, and exhalation of the brine into a reduced environment on the sea floor produced a brine pool from which the regionally extensive (>5km) Zn-Pb-Ag ore was precipitated.Both ore types are characterized by significant spread in δ³⁴S, with the sulfur in the Cu ore and associate marble-hosted Zn mineralization on average being somewhat heavier (δ³⁴S=−4.7 to +10.5‰, average 3.9‰) than that in the stratiform Zn-Pb-Ag ore (δ³⁴S=−6 to +17‰, average 2.0‰). The ranges in δ³⁴S are significantly larger than those observed in syn-volcanic massive sulfide deposits in Bergslagen, for which simple magmatic/volcanic sulfur sources have been invoked. Mixing of magmatic-volcanic sulfur leached from underlying volcanic rocks and sulfur sourced from abiotic or bacterial sulfate reduction in a mixing zone at the seafloor could explain the range observed at Zinkgruvan.A distinct discontinuity in the stratigraphy, at which key stratigraphic units stop abruptly, is interpreted as a syn-sedimentary fault. Metal zonation in the stratiform ore (decreasing Zn/Pb from distal to proximal) and the spatial distribution of Cu mineralization in underlying dolomitic marble suggest that this fault was a major feeder to the mineralization. Our interpretation of ore-forming fluid composition and a dominant redox trap rather than a pH and/or temperature trap differs from most VMS models, with Selwyn-type SEDEX models, and most BHT models. Zinkgruvan has similarities to both McArthur-type SEDEX deposits and sediment-hosted Cu deposits in terms of the inferred ore fluid chemistry, yet the basinal setting has more similarities to BHT and felsic-bimodal VMS districts. We speculate that besides an oxidized footwall stratigraphy, regionally extensive banded iron formations and limestone horizons in the Bergslagen stratigraphy may have aided in buffering ore-forming brines to oxidized, near-neutral conditions. In terms of fluid chemistry, Zinkgruvan could comprise one of the oldest known manifestations of Zn and Cu ore-forming systems involving oxidized near-neutral brines following oxygenation of the Earth's atmosphere.

Graphical abstract

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Fabrication and properties of pure-phase Cu2O co-doped with zinc and indium

Publication date: 15 March 2017
Source:Journal of Alloys and Compounds, Volume 697
Author(s): Xing-Min Cai, Xiao-Qiang Su, Fan Ye, V.A.L. Roy, Dong-Ping Zhang, Jing-Ting Luo, Ping Fan, Zhuang-Hao Zheng, Guang-Xing Liang, Jun-Jun Xiao
Cuprous oxide (Cu2O) thin films co-doped with zinc (Zn) and indium (In) were fabricated with direct current (DC) magnetron sputtering. The sputtering voltage of the Cu target was fixed while that of the alloy target of Zn and In was varied. It is found that when the alloy target voltage is below 310 V, pure-phase Cu2O can be obtained while a further increase in the alloy target voltage will result in the presence of metallic copper. The surface morphologies, the atomic ratios of the Zn and In, and the grain size do not have a linear dependence on the sputtering voltage of the alloy target. Higher concentration doping will decrease the lattice constant of Cu2O. Pure-phase samples doped with Zn and In have relatively higher transmittance and larger optical band gaps. The n-type conduction of Cu2O co-doped with Zn and In is realized when the sputtering voltage of the alloy target is 310 V. Zn and In atoms are found to exist as Zn²⁺ and In³⁺ in the films and they are possible donors for the n-type conduction.



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INF-{gamma} encoding plasmid administration triggers bone loss and disrupts bone marrow microenvironment

IFN- is a pleotropic cytokine produced in the bone microenvironment. Although IFN- is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN- recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN- encoding plasmid (pIFN-) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis. Ovariectomy produced a dramatic decrease of bone mineral density (BMD). pINF- injected mice showed a pathologic bone and bone marrow phenotype; the disrupted cortical and trabecular bone microarchitecture was accompanied by an increased release of pro-inflammatory cytokine by bone marrow cells. Moreover, mesenchymal stem cells' (MSCs) commitment to osteoblast was found impaired, as evidenced by the decline of osterix-positive (Osx⁺) cells within the mid-diaphyseal area of femurs. For instance, a reduction and redistribution of CXCL12 cells have been found, in accordance with bone marrow morphological alterations. As similar effects were observed both in sham-operated and in ovariectomized mice, our studies proved that an increased IFN- synthesis in bone marrow might be sufficient to induce inflammatory and catabolic responses even in the absence of pathologic predisposing substrates. In addition, the obtained data might raise questions about pIFN-'s safety when it is used as vaccine adjuvant.

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Islet adaptations in fetal sheep persist following chronic exposure to high norepinephrine

Complications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α₂-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion after chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at 129 ± 1 days of gestation, fetuses were continuously infused for seven days with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS studies were performed again on days 8 and 12. Adrenergic sensitivity was determined in pancreatic islets collected at day 12. NE infusion increased (P < 0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P < 0.05) in NE-infused fetuses compared to controls at both one and five days after discontinuing the infusion. Glucose-potentiated arginine-induced insulin secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than controls, but islet insulin content and intracellular calcium signaling were not different between treatments. The half-maximal inhibitory concentration for NE was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These findings show that chronic NE exposure and not hyperglycemia produce persistent adaptations in pancreatic islets that augment β-cell responsiveness in part through decreased adrenergic sensitivity.

http://ift.tt/2hNY0cI

17{beta}-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B

Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17β-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects. In ovariectomized (OVX) rats (half of which were treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and function, increased oxidative stress, and defective lipid metabolism, but was counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing mitochondrial biogenesis and function was confirmed. These effects were unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was knocked down by specific siRNA. Our results reveal a widespread protective role of E2 in hepatocytes, which is explained by enhanced mitochondrial content and oxidative capacity, lower hepatic lipid accumulation, and a reduction of oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a modulator of E2 effects on mitochondrial biogenesis and function supporting activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders.

http://ift.tt/2hNTomJ

11{beta}-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet

The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched 'Western' diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae. Our results demonstrate that (i) genetic effects on host–microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency.

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Mohawk transcription factor regulates homeostasis of the periodontal ligament [RESEARCH ARTICLE]

Naoki Koda, Tempei Sato, Masahiro Shinohara, Shizuko Ichinose, Yoshiaki Ito, Ryo Nakamichi, Tomohiro Kayama, Kensuke Kataoka, Hidetsugu Suzuki, Keiji Moriyama, and Hiroshi Asahara

The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well-known. We report that Mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and 12 months. In Mkx^–/– mice, age-dependent expansion of the PDL at the maxillary 1^st molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx^–/– mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx^+/+ mice. PDL cells lost their shape in Mkx^–/– mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx^–/– PDL revealed an increase in osteogenic gene expression and no change in PDL- and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkx-overexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis.

http://ift.tt/2gW815K

The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine-cell specification and postnatal {beta}-cell maturation [RESEARCH ARTICLE]

Yu-Ping Yang, Mark A. Magnuson, Roland Stein, and Christopher V.E. Wright

Much evidence supports the idea that the Pdx1 transcription factor is required for multiple aspects of pancreatic organogenesis, including early growth of the entire pancreatic epithelium, islet β-cell lineage allocation, and maintenance of fate and function in adult β cells. It remains unclear, however, to what extent Pdx1 expression and function depend upon trans-activation focused through 5' upstream conserved cis-regulatory regions and, in particular, if the mammal-specific Area II (located at -2139 to -1958 bp) affects minor or major aspects of organogenesis. We show that Area II is a primary effector of endocrine-selective transcription in epithelial multipotent cells, nascent endocrine progenitors, and differentiating and mature β cells in vivo. Pdx1^AREAII/NULL mice exhibited a massive reduction in endocrine progenitor cells and progeny hormone-producing cells, indicating Area II activity as fundamental to mounting an effective endocrine lineage-specification program within the multipotent cell population. Moreover, creating an Area II-deleted state within already-specified Neurog3-expressing endocrine-progenitor cells increased the proportion of glucagon⁺ α relative to insulin⁺β cells, associated with the transcriptional and epigenetic derepression of the α-cell-determining Arx gene in endocrine progenitors. There were also glucagon/insulin coexpressing cells, and β cells that were incapable of maturation. Creating the Pdx1^AREAII state after cells entered an insulin-expressing stage also led to immature and dysfunctional islet β cells carrying abnormal chromatin marking in vital β-cell-associated genes. Therefore, trans-regulatory integration through the mammal-restricted Area II mediates a surprisingly extensive range of progenitor and β-cell-specific functions of the Pdx1 gene.

http://ift.tt/2gVV4ZA

MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocyte [RESEARCH ARTICLE]

Qian-Qian Sha, Xing-Xing Dai, Yujiao Dang, Fuchou Tang, Junping Liu, Yin-Li Zhang, and Heng-Yu Fan

Mammalian oocyte maturation depends on the translational activation of stored maternal mRNAs upon meiotic resumption. Cytoplasmic polyadenylation element binding protein-1 (CPEB1) is a key oocyte factor that regulates maternal mRNA translation. However, the signal that triggers CPEB1 activation at the onset of mammalian oocyte maturation is not known. We provide evidence that a mitogen-activated protein kinase (MAPK) cascade couples maternal mRNA translation to meiotic cell cycle progression in mouse oocytes, by triggering CPEB1 phosphorylation and degradation. Mutations of the phosphorylation sites or ubiquitin E3 ligase binding sites in CPEB1 have a dominant negative effect in oocytes, and mimic the phenotype of ERK1/2 knockout, by impairing spindle assembly and mRNA translation. Overexpression of the CPEB1-downstream translation activator DAZL in ERK1/2-deficient oocytes partially rescued the meiotic defects, indicating that ERK1/2 is essential for spindle assembly, metaphase II arrest, and maternal-zygotic transition (MZT) primarily by triggering the translation of key maternal mRNAs. Taken together, ERK1/2-mediated CPEB1 phosphorylation/degradation is a major mechanism of maternal mRNA translational activation, and is crucial for mouse oocyte maturation and MZT.

http://ift.tt/2i3ExaK

TAEL: A zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control [TECHNIQUES AND RESOURCES ARTICLE]

Anna Reade, Laura B. Motta-Mena, Kevin H. Gardner, Didier Y. Stainier, Orion D. Weiner, and Stephanie Woo

Here we describe an optogenetic gene expression system optimized for use in zebrafish. This system overcomes the limitations of current inducible expression systems by enabling robust spatial and temporal regulation of gene expression in living organisms. Because existing optogenetic systems show toxicity in zebrafish, we re-engineered the blue-light activated EL222 system, renamed TAEL, for minimal toxicity while exhibiting a large range of induction, fine spatial precision, and rapid kinetics. We validate several strategies to spatially restrict illumination and thus gene induction with the TAEL system. As a functional example, we show that TAEL is able to induce ectopic endodermal cells in the presumptive ectoderm via targeted sox32 induction. We also demonstrate that TAEL can be used to resolve multiple roles of Nodal signaling at different stages of embryonic development. Finally, we show how inducible gene editing can be achieved by combining the TAEL and CRISPR/Cas9 systems. This toolkit should be a broadly useful resource for the fish community.

http://ift.tt/2gWbdhI

Patterning of brain precursors in ascidian embryos [RESEARCH REPORT]

Rosaria Esposito, Hitoyoshi Yasuo, Cathy Sirour, Antonio Palladino, Antonietta Spagnuolo, and Clare Hudson

In terms of their embryonic origins, the anterior and posterior parts of the ascidian central nervous system (CNS) are associated with distinct germ layers. The anterior part of the sensory vesicle, or brain, originates from ectoderm lineages following a neuro-epidermal binary fate decision. In contrast, a large part of the remaining posterior CNS is generated following neuro-mesodermal binary fate decisions. Here, we address the mechanisms that pattern the anterior brain precursors along the medial-lateral axis (future dorsal-ventral) at neural plate stages. Our functional studies show that Nodal signals are required for induction of lateral genes including Delta-like, Snail, Msxb and Trp. Delta-like/Notch signalling induces intermediate (Gsx) over medial (Meis) gene expression in intermediate cells, while the combinatorial action of Snail and Msxb prevents the expression of Gsx in lateral cells. We conclude that despite the distinct embryonic lineage origins within the larval CNS, the mechanisms that pattern neural precursors are remarkably similar.

http://ift.tt/2i3EkV7

A vertebrate specific and essential role for sp7/osterix in osteogenesis revealed by gene knock-out in the teleost medaka [RESEARCH REPORT]

Tingsheng Yu, Martin Graf, Joerg Renn, Manfred Schartl, Daria Larionova, Ann Huysseune, Paul Eckhard Witten, and Christoph Winkler

Sp7/osterix (osx) encodes a zinc-finger transcription factor that controls osteoblast differentiation in mammals. Although identified in all vertebrate lineages, its role in non-mammalian bone formation remains elusive. Here we show that an osx mutation in medaka results in severe bone defects and larval lethality. Pre-osteoblasts fail to differentiate leading to severe intramembranous and perichondral ossification defects. The notochord sheath mineralizes normally supporting the idea of an osteoblast-independent mechanism for teleost vertebral centra formation. This study establishes a key role for Sp7/Osx for bone formation also in a non-mammalian species, and reveals conserved and non-conserved features in vertebrate bone formation.

http://ift.tt/2gW6yfL

mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis [RESEARCH ARTICLE]

Philippe Foerster, Marie Daclin, Shihavuddin Asm, Marion Faucourt, Alessandra Boletta, Auguste Genovesio, and Nathalie Spassky

Radial glial cells (RCG) are self-renewing progenitor cells that give rise to neurons and glia during embryonic development. Throughout neurogenesis, these cells contact the cerebral ventricles and bear a primary cilium. Although the role of the primary cilium in embryonic patterning has been studied, its role in brain ventricular morphogenesis is poorly characterized. Using conditional mutants, we show that the primary cilia of radial glia determine the size of the surface of their ventricular apical domain through regulation of the mTORC1 pathway. In cilium-less mutants, the orientation of the mitotic spindle in radial glia is also significantly perturbed and associated with an increased number of basal progenitors. The enlarged apical domain of RGC leads to dilatation of the brain ventricles during late embryonic stages (ventriculomegaly), which initiates hydrocephalus during postnatal stages. These phenotypes can all be significantly rescued by treatment with the mTORC1 inhibitor rapamycin. These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus.

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Ascl2 inhibits myogenesis by antagonizing the transcriptional activity of myogenic regulatory factors [RESEARCH ARTICLE]

Chao Wang, Min Wang, Justine Arrington, Tizhong Shan, Feng Yue, Yaohui Nie, Weiguo Andy Tao, and Shihuan Kuang

Myogenic regulatory factors (MRFs) including Myf5, MyoD and Myog are muscle-specific transcriptional factors orchestrating myogenesis. Although MRFs are essential for myogenic commitment and differentiation, timely repression of their activity is necessary for self-renewal and maintenance of muscle stem cells (satellite cells). Here we define a novel inhibitor of MRFs: the achaete-scute homologue 2 (Ascl2). During development, Ascl2 is transiently detected in a subpopulation of Pax7⁺MyoD⁺ progenitors (myoblasts) that become Pax7⁺MyoD^– satellite cells prior to birth, but not detectable in postnatal satellite cells. Knockout of Ascl2 in embryonic myoblasts decreases both the number of Pax7⁺ cells and the proportion of Pax7⁺MyoD^– cells. Conversely, overexpression of Ascl2 inhibits the proliferation and differentiation of cultured myoblasts, and impairs regeneration of injured muscles. At the molecular level, Ascl2 competes with MRFs for binding to E-boxes in the promoters of muscle genes, without activating gene transcription. Ascl2 also forms heterodimer with classical E-proteins to sequester their transcriptional activity on MRFs. Accordingly, MyoD or Myog expression rescues myogenic differentiation despite Ascl2 overexpression. Finally, Ascl2 expression is regulated by Notch signaling, a key governor of satellite cell self-renewal. These data together demonstrate that Ascl2 inhibits myogenic differentiation by targeting MRFs, and facilitates generation of postnatal satellite cells.

http://ift.tt/2gWfp0F

An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation [RESEARCH ARTICLE]

Melanie Rothe, Noreen Kanwal, Petra Dietmann, Franziska Seigfried, Annemarie Hempel, Desiree Schütz, Dominik Reim, Rebecca Engels, Alexander Linnemann, Michael J. Schmeisser, Juergen Bockmann, Michael Kühl, Tobias M. Boeckers, and Susanne J. Kühl

The signal-induced proliferation associated family of proteins comprises four members, SIPA1 and SIPA1L1-1L3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts up-stream of Sipa1l3 during eye development. Both, Sipa1l3 and Epha4 are required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax. We demonstrated that canonical Wnt signaling is inhibited downstream of Epha4/Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an up-regulation of axin2 expression, a direct Wnt/β-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/β-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells resulting in congenital cataracts.

http://ift.tt/2gVX3Nm

Prdm16 is critical for progression of the multipolar phase during neural differentiation of the developing neocortex [RESEARCH ARTICLE]

Mayuko Inoue, Ryota Iwai, Hidenori Tabata, Daijiro Konno, Mariko Komabayashi-Suzuki, Chisato Watanabe, Hiroko Iwanari, Yasuhiro Mochizuki, Takao Hamakubo, Fumio Matsuzaki, Koh-ichi Nagata, and Ken-ichi Mizutani

The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in mitochondrial reactive oxygen species (mtROS) levels, depending on cell requirements. We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone. However, Prdm16 expression declined during the transition into NeuroD1-positive multipolar cells. Subsequently, repression of Prdm16 expression by NeuroD1 on the periphery of ventricular zone was crucial for appropriate progression of the multipolar phase and was required for normal cellular development. Furthermore, time-lapse imaging experiments revealed abnormal migration and morphological changes in Prdm16-overexpressing and -knockdown cells. Reporter assays and mtROS determinations demonstrated that PGC-1α is a major downstream effector of Prdm16 and NeuroD1, and is required for regulation of the multipolar phase and characteristic modes of migration. Taken together, these data suggest that Prdm16 plays an important role in dynamic cellular redox changes in developing neocortex during neural differentiation.

http://ift.tt/2i3Ba3L

Genetic mosaics and time-lapse imaging identify functions of H3.3 residues in mouse oocytes and embryos [TECHNIQUES AND RESOURCES ARTICLE]

Liquan Zhou, Boris Baibakov, Bertram Canagarajah, Bo Xiong, and Jurrien Dean

During development from oocyte to embryo, genetic programs in mouse germ cells are reshaped by chromatin remodeling to orchestrate the onset of development. Epigenetic modifications of specific amino-acid residues of core histones and their isoforms can dramatically alter activation and suppression of gene expression. H3.3 is a histone H3 variant that plays essential roles in mouse oocytes and early embryos, but the functional role of individual amino acid residues has been unclear because of technical hurdles. Here, we describe two strategies that successfully investigated the functions of three individual H3.3 residues in oogenesis, cleavage-stage embryogenesis and early development. We first generated genetic mosaic ovaries and blastocysts with stochastic expression of wild-type or mutant H3.3 alleles to document dominant negative effects of H3.3R26 and H3.3K27 in modulating oogenesis and partitioning cells to the inner cell mass of the early embryo. We also established time-lapse imaging assays to document essential roles of H3.3K56 in efficient H2B incorporation and paternal pronuclei formation. We demonstrate that application of these strategies can be extended to investigate roles of additional H3.3 residues and have implications for use in other developmental systems.

http://ift.tt/2gVWWRW

Derivation of a robust mouse mammary organoid system for studying tissue dynamics [RESEARCH REPORT]

Paul R. Jamieson, Johanna F. Dekkers, Anne C. Rios, Nai Yang Fu, Geoffrey J. Lindeman, and Jane E. Visvader

Advances in stem cell research have enabled the generation of mini-organs or organoids that recapitulate phenotypic traits of the original biological specimen. Although organoids have been demonstrated for multiple organ systems, there are more limited options for studying mouse mammary gland formation in vitro. Here we have built upon previously described culture assays to define culture conditions that enable the efficient generation of clonal organoid structures from single-sorted basal mammary epithelial cells (MECs). Analysis of Confetti-reporter mice revealed the formation of uni-coloured structures and thus the clonal nature of these organoids. High resolution 3D imaging demonstrated that basal cell-derived, complex organoids comprised an inner compartment of polarized luminal cells with milk-producing capacity and an outer network of elongated myoepithelial cells. Conversely, structures generated from luminal MECs rarely contained basal/myoepithelial cells. Moreover, flow cytometry and 3D microscopy of organoids generated from lineage-specific reporter mice established the bipotent capacity of basal cells and the restricted potential of luminal cells. In summary, we describe optimized in vitro conditions for the efficient generation of mouse mammary organoids that recapitulate features of mammary tissue architecture and function, and can be applied to understand tissue dynamics and cell-fate decisions.

http://ift.tt/2gW7u3p

CenpH regulates meiotic G2/M transition by modulating the APC/CCdh1-cyclin B1 pathway in oocytes [RESEARCH ARTICLE]

Teng Zhang, Yang Zhou, Li Li, Zhen-Bo Wang, Wei Shen, Heide Schatten, and Qing-Yuan Sun

Meiotic resumption (G2/M transition) and progression through meiosis I (MI) are two critical stages for producing fertilization-competent eggs. Here, we report that CenpH, a component of the kinetochore inner plate protein, is responsible for the G2/M transition in meiotic mouse oocytes. Depletion of CenpH using morpholino injection decreased cyclin B1 levels, resulting in an attenuation of MPF activation, and severely compromised the meiotic resumption. CenpH protects cyclin B1 from destruction by competing actions of APC/C^Cdh1. Impaired G2/M transition after CenpH depletion could be rescued by expression of exogenous cyclin B1. Unexpectedly, blocking of CenpH did not affect spindle organization and meiotic cell cycle progression after germinal vesicle breakdown. Our findings reveal a novel role of CenpH in regulating meiotic G2/M transition by acting via the APC/C^Cdh1-cyclin B1 pathway.

http://ift.tt/2i3CZhb

Osteocrin, a peptide secreted from the heart and other tissues, contributes to cranial osteogenesis and chondrogenesis in zebrafish [RESEARCH ARTICLE]

Ayano Chiba, Haruko Watanabe-Takano, Kenta Terai, Hajime Fukui, Takahiro Miyazaki, Mami Uemura, Hisashi Hashimoto, Masahiko Hibi, Shigetomo Fukuhara, and Naoki Mochizuki

The heart is an endocrine organ, because cardiomyocytes (CMs) secrete natriuretic peptide (NP) hormones. Since the discovery of NPs, no peptide hormones that affect remote organs have been identified from the heart. We identified osteocrine (Ostn) as an osteogenesis/chondrogenesis regulatory hormone secreted from CMs in zebrafish. The ostn mutant larvae exhibited impaired membranous and chondral bone formation. The impaired bones were recovered by CM-specific overexpression of Ostn. We analyzed parasphenoid (ps) as a representative of membranous bones. In the shortened ps of the ostn morphants, nuclear Yap1/Wwtr1-dependent transcription was increased, suggesting that Ostn might induce the nuclear export of Yap1/Wwtr1 in osteoblasts. Although OSTN is proposed to bind to NPR3 (clearance receptor for NPs) to enhance the binding of NPs to NPR1 or NPR2, OSTN enhanced C-type NP-dependent nuclear export of YAP1/WWTR1 of cultured osteoblasts stimulated with saturable CNP. OSTN, therefore, might activate unidentified receptors that augment protein kinase G signaling mediated by a CNP-NPR2 signaling axis. These data demonstrate that Ostn secreted from the heart contributes to bone formation as an endocrine hormone.

http://ift.tt/2gVXBTz

Direct induction of neural progenitor cells transiently passes through a partially reprogrammed state

Publication date: March 2017
Source:Biomaterials, Volume 119
Author(s): Rui Gao, Wenchao Xiu, Linfeng Zhang, Ruge Zang, Lei Yang, Chenfei Wang, Min Wang, Mingzhu Wang, Li Yi, Yuanyuan Tang, Yawei Gao, Hong Wang, Jiajie Xi, Wenqiang Liu, Yixuan Wang, Xuejun Wen, Yongchun Yu, Yong Zhang, Liang Chen, Jiayu Chen, Shaorong Gao
The generation of functional neural progenitor cells (NPCs) holds great promise for both research and clinical applications in neurodegenerative diseases. Traditionally, NPCs are derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), or NPCs can be directly converted from somatic cells by sets of transcription factors or by a combination of chemical cocktails and/or hypoxia. However, the ethical issues of ESCs, the risk of tumorigenesis from iPSCs and transgenic integration from exogenous genes as well as complicated manipulation and time-consuming of chemical induced NPCs (ciNPCs) limit the applications of these strategies. Here, we describe a novel method for generating growth factor-induced neural progenitor cells (giNPCs) from mouse embryonic and adult fibroblasts by using inductive and/or permissive signaling culture conditions. These giNPCs closely resemble brain-derived NPCs in terms of transcription networks and neural lineage differentiation potentials. Moreover, this somatic cell to NPC induction is a gradual process that includes initiation, intermediate, maturation and stabilization stages. Importantly, gene expression and histone modification analyses further indicate a partially reprogrammed state during the generation process of induced NPCs, in which lineage specific genes and pluripotency associated genes are transiently activated. Our study therefore describes the potential safety problems that also exist in the transgene-free direct induction strategy and highlights the importance of excluding the possibility of residual partially reprogrammed and/or teratoma-like cells from the generated NPCs for future clinical trials.



http://ift.tt/2hibuMB

Different doses of dexmedetomidine reduce plasma cytokine production, brain oxidative injury, PARP and caspase expression levels but increase liver oxidative toxicity in cerebral ischemia-induced rats

Publication date: Available online 19 December 2016
Source:Brain Research Bulletin
Author(s): Orhan Akpınar, Mustafa Nazıroğlu, Hatice Akpınar
Cerebral ischemia-induced progression of brain, liver, and erythrocyte oxidative injuries might be modulated by dexmedetomidine (DEX) as a potent antioxidant and anti-inflammatory drug. The present study was conducted to explore whether two different doses of DEX protect against plasma cytokine and brain, liver and erythrocyte oxidative toxicity and apoptosis in cerebral ischemia-induced rats.Forty-two rats were equally divided into 7 groups. The first and second groups were used as untreated and sham controls, respectively. The third (DEX4) and fourth (DEX40) groups received 4mg/kg and 40mg/kg DEX treatments. The fifth, sixth and seventh group were operated on to induce cerebral ischemia. The fifth, sixth and seventh groups are used to represent cerebral ischemia, cerebral ischemia+DEX4, and cerebral ischemia+DEX40, respectively. DEX was intraperitoneally given to the DEX groups at the 3rd, 24th and 48th hour.Brain and erythrocyte lipid peroxidation (MDA) levels and plasma IL-1β and TNF-α levels were high in the cerebral ischemia group although they were low in the DEX4 and DEX40 groups. Decreased glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) values in the brain and erythrocyte of the cerebral ischemia group were increased by the DEX treatments, although PARP, and the caspase 3 and 9 expressions in the brain were further decreased. Conversely, the cerebral ischemia-induced decrease in the liver vitamin A, vitamin E, GSH, and GSH-Px were further decreased by the DEX treatments, although MDA level, PARP, and caspase 3 and 9 expressions were further increased by the DEX treatments.In conclusion, DEX induced protective effects against cerebral ischemia-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production. However, both doses of DEX induced oxidative toxicity and apoptotic effects in the rats' livers.



http://ift.tt/2hBZ0m6

Resuscitation Science in Circulation: A Timely Topic.

Author: Diercks, Deborah B. MD; Al-Khatib, Sana M. MD, MHS; Link, Mark S. MD

Page: 2033-2034

http://ift.tt/2h5X71W

Stop Randomizing All Cardiac Arrests.

Author: Weisfeldt, Myron L. MD

Page: 2035-2036

http://ift.tt/2hlanvW

Doubling Cardiac Arrest Survival by 2020: Achieving the American Heart Association Impact Goal.

Author: Neumar, Robert W. MD, PhD

Page: 2037-2039

http://ift.tt/2h62X3F

Improving Care of Out-of-Hospital Cardiac Arrest: Next Steps.

Author: Jollis, James G. MD; Granger, Christopher B. MD

Page: 2040-2042

http://ift.tt/2hl3ryZ

Measured Progress in Cardiopulmonary Resuscitation.

Author: Hazinski, Mary Fran RN, MSN

Page: 2043-2045

http://ift.tt/2h5X4U4

Duration of Prehospital Cardiopulmonary Resuscitation and Favorable Neurological Outcomes for Pediatric Out-of-Hospital Cardiac Arrests: A Nationwide, Population-Based Cohort Study.

Author: Goto, Yoshikazu MD, PhD; Funada, Akira MD, PhD; Goto, Yumiko MD, PhD

Page: 2046-2059

http://ift.tt/2h61H0k

Conventional Versus Compression-Only Versus No-Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest.

Author: Fukuda, Tatsuma MD, PhD; Ohashi-Fukuda, Naoko MD; Kobayashi, Hiroaki MD; Gunshin, Masataka MD; Sera, Toshiki MD, PhD; Kondo, Yutaka MD, PhD; Yahagi, Naoki MD, PhD

Page: 2060-2070

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Is It Time to Stop Teaching Bystanders Ventilation as Part of Pediatric Cardiopulmonary Resuscitation?.

Author: de Caen, Allan MD; Tijssen, Janice A. MD

Page: 2071-2073

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Identifying Patients at Risk for Prehospital Sudden Cardiac Arrest at the Early Phase of Myocardial Infarction: The e-MUST Study (Evaluation en Medecine d'Urgence des Strategies Therapeutiques des infarctus du myocarde).

Author: Karam, Nicole MD, MPH; Bataille, Sophie MD; Marijon, Eloi MD, PhD; Giovannetti, Olivier MD, MPH; Tafflet, Muriel MPH; Savary, Dominique MD; Benamer, Hakim MD; Caussin, Christophe MD; Garot, Philippe MD; Juliard, Jean-Michel MD; Pires, Virginie MD; Boche, Thevy MD; Dupas, Francois MD; Le Bail, Gaelle MD; Lamhaut, Lionel MD, MPH; Laborne, Francois MD; Lefort, Hugues MD; Mapouata, Mireille MD; Lapostolle, Frederic MD; Spaulding, Christian MD, PhD; Empana, Jean-Philippe MD, PhD; Jouven, Xavier MD, PhD; Lambert, Yves MD; For the e-MUST Study Investigators

Page: 2074-2083

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Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation.

Author: Reynolds, Joshua C. MD, MS; Grunau, Brian E. MD; Rittenberger, Jon C. MD, MS; Sawyer, Kelly N. MD, MS; Kurz, Michael C. MD, MS; Callaway, Clifton W. MD, PhD

Page: 2084-2094

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Association of Bystander Cardiopulmonary Resuscitation and Survival According to Ambulance Response Times After Out-of-Hospital Cardiac Arrest.

Author: Rajan, Shahzleen MD; Wissenberg, Mads MD, PhD; Folke, Fredrik MD, PhD; Hansen, Steen Moller MD; Gerds, Thomas A. PhD; Kragholm, Kristian MD, PhD; Hansen, Carolina Malta MD, PhD; Karlsson, Lena MD; Lippert, Freddy K. MD; Kober, Lars MD, DSc; Gislason, Gunnar H. MD, PhD; Torp-Pedersen, Christian MD, DSc

Page: 2095-2104

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Hospital Variation in Time to Epinephrine for Nonshockable In-Hospital Cardiac Arrest.

Author: Khera, Rohan MD; Chan, Paul S. MD, MSc; Donnino, Michael MD; Girotra, Saket MD, SM; For the American Heart Association's Get With The Guidelines-Resuscitation Investigators

Page: 2105-2114

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Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial.

Author: Wiberg, Sebastian MD; Hassager, Christian MD, DMSc; Schmidt, Henrik MD, DMSc; Thomsen, Jakob Hartvig MD; Frydland, Martin MD; Lindholm, Matias Greve MD, PhD; Hofsten, Dan Eik MD, PhD; Engstrom, Thomas MD, PhD, DMSc; Kober, Lars MD, DMSc; Moller, Jacob Eifer MD, PhD, DMSc; Kjaergaard, Jesper MD, PhD, DMSc

Page: 2115-2124

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Late-Breaking Clinical Trial Abstracts From the American Heart Association's Scientific Sessions 2016.

Author:

Page: e702-e708

http://ift.tt/2hkZhXu

Late-Breaking Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016.

Author:

Page: e709-e715

http://ift.tt/2h64FSr

Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Author:

Page: e716-e720

http://ift.tt/2h5S2qG

Factors Associated With Pulmonary Embolism-Related Sudden Cardiac Arrest.

Author: Bougouin, Wulfran MD; Marijon, Eloi MD, PhD; Planquette, Benjamin MD; Karam, Nicole MD; Dumas, Florence MD, PhD; Celermajer, David S. PhD; Jost, Daniel MD; Lamhaut, Lionel MD, PhD; Beganton, Frankie MS; Cariou, Alain MD, PhD; Meyer, Guy MD, PhD; Jouven, Xavier MD, PhD; On behalf of the Sudden Death Expertise Center

Page: 2125-2127

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Ticagrelor Versus Clopidogrel in Comatose Survivors of Out-of-Hospital Cardiac Arrest Undergoing Percutaneous Coronary Intervention and Hypothermia: A Randomized Study.

Author: Steblovnik, Klemen MD, PhD; Blinc, Ales MD, PhD; Mijovski, Mojca Bozic PhD; Fister, Misa MD, PhD; Mikuz, Ursa MD; Noc, Marko MD, PhD

Page: 2128-2130

http://ift.tt/2h5ZIcl

Association of Mechanical Cardiopulmonary Resuscitation Device Use With Cardiac Arrest Outcomes: A Population-Based Study Using the CARES Registry (Cardiac Arrest Registry to Enhance Survival).

Author: Buckler, David G. NRP; Burke, Rita V. PhD, MPH; Naim, Maryam Y. MD; MacPherson, Andrew MD; Bradley, Richard N. MD; Abella, Benjamin S. MD, MPhil; Rossano, Joseph W. MD, MS; For the CARES Surveillance Group

Page: 2131-2133

http://ift.tt/2hl31Zr

Advantages of time-resolved fluorescent nanobeads compared with fluorescent submicrospheres, quantum dots, and colloidal gold as label in lateral flow assays for detection of ractopamine

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Li-Ming Hu, Kai Luo, Jun Xia, Guo-Mao Xu, Cheng-Hui Wu, Jiao-Jiao Han, Gang-Gang Zhang, Miao Liu, Wei-Hua Lai
Label selection is a critical factor for improving the sensitivity of lateral flow assay. Time-resolved fluorescent nanobeads, fluorescent submicrospheres, quantum dots, and colloidal gold-based lateral flow assay (TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA) were first systematically compared for the quantitative detection of ractopamine in swine urine based on competitive format. The limits of detection (LOD) of TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA were 7.2, 14.7, 23.6, and 40.1pg/mL in swine urine samples, respectively. The sensitivity of TRFN-LFA was highest. In the quantitative determination of ractopamine (RAC) in swine urine samples, TRFN-LFA exhibited a wide linear range of 5pg/mL to 2500pg/mL with a reliable coefficient of correlation (R²=0.9803). Relatively narrow linear ranges of 10–500pg/mL (FM-LFA) and 25–2500pg/mL (QD-LFA and CG-LFA) were acquired. Approximately 0.005µg of anti-RAC poly antibody (pAb) was used in each TRFN-LFA test strip, whereas 0.02, 0.054, and 0.15µg of pAb were used in each of the FM-LFA, QD-LFA, and CG-LFA test strips, respectively. In addition, TRFN-LFA required the least RAC-BSA antigens and exhibited the shortest detection time compared with the other lateral flow assays. Analysis of the RAC in swine urine samples showed that the result of TRFN-LFA was consistent with that of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a commercial enzyme-linked immunosorbent assay (ELISA) kit.



http://ift.tt/2gW5esV

Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Chun Xiao, Qingping Wu, Jumei Zhang, Yizhen Xie, Wen Cai, Jianbin Tan
Ethnopharmacological relevanceGanoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action.Materials and methodsFour polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC–MS spectroscopy,ResultsF31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin.ConclusionData suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These results strongly suggest that F31 has antidiabetic potential.

Graphical abstract

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Spasmogenic and spasmolytic activities of Agastache mexicana ssp. mexicana and A. mexicana ssp. xolocotziana methanolic extracts on the guinea pig ileum

Publication date: 20 January 2017
Source:Journal of Ethnopharmacology, Volume 196
Author(s): Rosa Ventura-Martínez, Rodolfo Rodríguez, María Eva González-Trujano, Guadalupe E. Ángeles-López, Myrna Déciga-Campos, Claudia Gómez
Ethnopharmacological relevanceAgastache mexicana has been used in traditional medicine for relief of abdominal pain and treatment of other diseases. Two subspecies have been identified: A. mexicana ssp. mexicana (AMM) and A. mexicana ssp. xolocotziana (AMX) and both are used traditionally without distinction or in combination.Aim of the studyTo determine the effect of methanol extracts of A. mexicana ssp. mexicana and A. mexicana ssp. xolocotziana on gut motility and their possible mechanism of action.Materials and methodsThe effect of AMM and AMX methanol extracts were tested on the spontaneous activity in the isolated guinea pig ileum and on tissues pre-contracted with KCl, electrical field stimulation (EFS) or ACh. In addition, the possible mechanism of action of each subspecies on gut motility was analyzed in the presence of hexametonium, indomethacin, L-NAME, verapamil, atropine or pyrylamine. A comparative chromatographic profile of these extracts was also done to indicate the most abundant flavonoids presents in methanol extracts of both subspecies.ResultsAMM, but not AMX, induced a contractile effect in the guinea pig ileum. This spasmogenic effect was partially inhibited by atropine, antagonist of muscarinic receptors; and pyrilamine, antagonist of H1 receptors. In contrast, AMX, but not AMM, diminished the contractions induced by KCl, EFS or ACh. The spasmolytic activity of AMX was partially inhibited by hexamethonium, ganglionic blocker; and indomethacin, inhibitor of the synthesis of prostaglandins; but not by L-NAME, inhibitor of nitric oxide synthase. In addition, AMX diminished the maximal contraction induced by CaCl2 in a calcium-free medium. Chromatographic analyses of these methanol extracts showed the presence of acacetin and tilanin in both.ConclusionsThese results suggest that in folk medicine only AMX should be used as spasmolytic, and not in combination with AMM as traditionally occurs, due to the spasmogenic effects of the latter. In addition, activation of nicotinic receptors, prostaglandins and calcium channels, but not nitric oxide mechanisms, could be responsible for the spasmolytic activity of AMX. On the other hand, release of ACh and histamine could be involved in the spasmogenic effect induced by AMM. Acacetin and tilanin are present in methanol extracts of both subspecies and both flavonoids were more abundant in AMX than AMM. Our findings contribute to the validation of the traditional use of Agastache mexicana in relieving gastrointestinal disorders, but indicate that the subspecie that should be used for this effect is A. mexicana ssp. xolocotziana.

Graphical abstract

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A Decade of Experience of Management of Thyroglossal Duct Cyst in a Tertiary Care Hospital: Differentiation Between Children and Adults

Abstract

Variations in thyroglossal duct cysts (TGDCs) between children and adult are mentioned very little in literature. The lesion mostly found in children but adult population also possesses this anomaly. The aim of this study was to determine the differences in clinical presentations and surgical outcomes of TGDC between children and adults. A retrospective chart review of all patients with TGDCs managed in our hospital from July 2004 to June 2014. All records were reviewed for age, sex, location of cyst in neck and with relation to hyoid bone, size, postoperative complication and recurrence rates. Differences between children and adults were assessed. A total of 39 patients (21 children and 18 adults) were treated for TGDC. Of the pediatric group, 71.4% were male and 28.5% were female, whereas 72.2% of the adults were male and 27.7% were female. Adults were more likely to develop other complaints like neck pain, dysphagia and dyspnea. Position was almost similar in both age groups with midline and infrahyoid location while laterality was seen in adult only. Size of Cyst was found to be larger in adults. The recurrence and post operative complication rates between children and adults were not significantly different. TGDC has male predominance. Clinical presentations were almost similar in both age groups. Although lateral deviation, increase size of cyst and recurrences were seen in adults only, Sistrunk procedure is recommended as a safe and standard surgical treatment in both age groups.

http://ift.tt/2hTAsCJ

A Decade of Experience of Management of Thyroglossal Duct Cyst in a Tertiary Care Hospital: Differentiation Between Children and Adults

Abstract

Variations in thyroglossal duct cysts (TGDCs) between children and adult are mentioned very little in literature. The lesion mostly found in children but adult population also possesses this anomaly. The aim of this study was to determine the differences in clinical presentations and surgical outcomes of TGDC between children and adults. A retrospective chart review of all patients with TGDCs managed in our hospital from July 2004 to June 2014. All records were reviewed for age, sex, location of cyst in neck and with relation to hyoid bone, size, postoperative complication and recurrence rates. Differences between children and adults were assessed. A total of 39 patients (21 children and 18 adults) were treated for TGDC. Of the pediatric group, 71.4% were male and 28.5% were female, whereas 72.2% of the adults were male and 27.7% were female. Adults were more likely to develop other complaints like neck pain, dysphagia and dyspnea. Position was almost similar in both age groups with midline and infrahyoid location while laterality was seen in adult only. Size of Cyst was found to be larger in adults. The recurrence and post operative complication rates between children and adults were not significantly different. TGDC has male predominance. Clinical presentations were almost similar in both age groups. Although lateral deviation, increase size of cyst and recurrences were seen in adults only, Sistrunk procedure is recommended as a safe and standard surgical treatment in both age groups.

http://ift.tt/2hTAsCJ

Thyroid High-Impact Articles

FREE ACCESS through January 2, 2017.
Read Now:

Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions
Carolin Stephanie Hoefig, Riccardo Zucchi, Josef Köhrle

Circulating 3-T1AM and 3, 5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study
Lies Langouche, Ina Lehmphul, Sarah Vander Perre, Josef Köhrle, Greet Van den Berghe

Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis
Johanna Wichman, Kristian Hillert Winther, Steen Joop Bonnema, Laszlo Hegedüs

Cervical Lymph Node Metastases After Thyroidectomy for Papillary Thyroid Carcinoma Usually Remain Stable for Years
Chisato Tomoda, Kiminori Sugino, Kenichi Matsuzu, Takashi Uruno, Keiko Ohkuwa, Wataru Kitagawa, Mitsuji Nagahama, Koichi Ito

Reference Intervals of Thyroid Function During Pregnancy: Self-Sequential Longitudinal Study Versus Cross-Sectional Study
Xiaomei Zhang, Baoting Yao, Chenyan Li, Jinyuan Mao, Weiwei Wang, Xiaochen Xie, Xiaochun Teng, Cheng Han, Weiwei Zhou, Chenyang Li, Bin Xu, Lihua Bi, Tao Meng, Jianling Du, Shaowei Zhang, Zhengnan Gao, Liu Yang, Chenling Fan, Weiping Teng, Zhongyan Shan

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Thyroid High-Impact Articles

FREE ACCESS through January 2, 2017.
Read Now:

Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions
Carolin Stephanie Hoefig, Riccardo Zucchi, Josef Köhrle

Circulating 3-T1AM and 3, 5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study
Lies Langouche, Ina Lehmphul, Sarah Vander Perre, Josef Köhrle, Greet Van den Berghe

Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis
Johanna Wichman, Kristian Hillert Winther, Steen Joop Bonnema, Laszlo Hegedüs

Cervical Lymph Node Metastases After Thyroidectomy for Papillary Thyroid Carcinoma Usually Remain Stable for Years
Chisato Tomoda, Kiminori Sugino, Kenichi Matsuzu, Takashi Uruno, Keiko Ohkuwa, Wataru Kitagawa, Mitsuji Nagahama, Koichi Ito

Reference Intervals of Thyroid Function During Pregnancy: Self-Sequential Longitudinal Study Versus Cross-Sectional Study
Xiaomei Zhang, Baoting Yao, Chenyan Li, Jinyuan Mao, Weiwei Wang, Xiaochen Xie, Xiaochun Teng, Cheng Han, Weiwei Zhou, Chenyang Li, Bin Xu, Lihua Bi, Tao Meng, Jianling Du, Shaowei Zhang, Zhengnan Gao, Liu Yang, Chenling Fan, Weiping Teng, Zhongyan Shan

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