The neural bases of ictal tachycardia in temporal lobe seizures

Temporal lobe epilepsy (TLE) can lead to intense changes in cardiac autonomic functions during both interictal and ictal periods (Lotufo et al., 2012; Eggleston et al., 2014). Tachycardia, defined as a decrease in the ECG R-R intervals (RR) (increase in heart rate), is the most common cardiac change occurring during epileptic seizures (Opherk and Hirsch, 2002; O'Regan and Brown, 2005; Toth et al., 2010) whereas bradycardia occurs in only 2% of them (Moseley et al., 2010). Tachycardia was proposed as a biomarker providing a somatic indicator of temporal lobe (TL) seizure onset (Osorio, 2014; Schiecke et al., 2014; Osorio and Manly, 2014; Jeppesen et al., 2015; Osorio and Manly, 2015; Behbahani et al., 2016; Van de Vel et al., 2016), opening the way to automatized and noninvasive seizure detection and treatment delivery prior to, or at the onset of, a TL seizure.

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Reversal of long term potentiation-like plasticity in primary motor cortex in patients with progressive supranuclear palsy

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder due to the deposition of tau-protein aggregates in several brain regions leading to parkinsonism, oculomotor abnormalities, early postural instability and falls. To date, the pathophysiological mechanisms of PSP are still poorly understood (Colosimo et al., 2014; Wenning et al., 2013).

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Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy

Nerve conduction studies (NCS) are a very useful tool in diagnosing polyneuropathy (PNP) both with respect to confirming the PNP and classifying it as primarily demyelinating or axonal (Donofrio and Albers, 1990; Tankisi et al., 2005). Since most PNPs follow a length dependent pattern, the sensory nerves of the feet are usually affected in the early stages (Oh et al., 2001; Park et al., 2003; Singleton et al., 2008; Singleton, 2005). The sural nerve is the most frequently examined nerve in the electrodiagnosis of PNP (Burke et al., 1974).

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Female Runner with Painful Left Thigh Swelling: A Case of May-Thurner Syndrome

We present a case of a female runner who presented with burning left groin and thigh pain and positional swelling following a long run. The workup revealed May-Thurner syndrome. May-Thurner syndrome anatomy is a common anatomical variant present in approximately 20% of the population. Compression of the iliac vein may result in venous stasis in the lower limb with a predisposition to deep venous thrombosis. We identify four reported cases of May-Thurner syndrome in female runners and review the importance of diagnosis and appropriate treatment of this condition.

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Measuring physical and cognitive fatigue in people with Post Polio Syndrome: development of the Neurological Fatigue Index for Post Polio Syndrome (NFI-PP)

Fatigue in Post Polio Syndrome (PPS) has been shown to adversely affect quality of life. There is currently no disease-specific measure of fatigue for PPS.

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Change of an Injured Corticospinal Tract During 3 Weeks' Rehabilitation After Putaminal Hemorrhage.

No abstract available

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Regarding: Radial Extracorporeal Shockwave Therapy Is No More Effective Than Placebo in the Management of Lateral Epicondylitis: A Double-Blind, Randomized, Placebo-Controlled Trial.

No abstract available

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What Is the Effect of Strength Training on Pain and Sleep in Patients With Fibromyalgia?.

Objective: The study aimed to investigate the effect of an 8-wk structured strength training program on pain and sleep quality in patients with fibromyalgia. Design: Fifty-two patients with fibromyalgia were evaluated; 31 submitted to strength training and 21 comprised the control group. The instruments used were the Fibromyalgia Impact Questionnaire and The Pittsburgh Sleep Quality Index. The questionnaires were applied before the first training session, at 12 sessions, and after 24 sessions. Descriptive statistics (mean, SD, and frequency) and inferential tests were used. Results: After 8 wks of intervention, significant differences were found between groups in subjective quality of sleep (P = 0.03), sleep disturbance (P = 0.02), daytime dysfunction (P = 0.04), and total sleep score (P

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Effects of Transcranial Direct Current Stimulation Plus Physical Therapy on Gait in Patients With Parkinson Disease: A Randomized Controlled Trial.

Objective: The aim of the study was to study the combined effects of transcranial direct current stimulation (tDCS) and physical therapy on the walking ability of patients with Parkinson disease (PD). Study Design: The study used an experimental, double-blinded, randomized controlled trial. Results: After intervention, group 1 (only tDCS) demonstrated a significant increase in gait speed by 0.13 to 0.14 m/sec (17.8%-19.2%) and an increase in step length by 5.9 to 6.1 cm (14.0%-14.5%), whereas group 2 (tDCS and physical therapy) revealed a significant increase in gait speed by 0.10 to 0.13 m/sec (14.9%-19.4%) and step length by 4.5 to 5.4 cm (10.6%-12.8%) and group 3 (sham tDCS and physical therapy) showed a significant increase in gait speed by 0.09 to 0.14 m/sec (13.0%-20.3%) and step length by 3.0 to 5.4 cm (6.8%-12.3%). All these results lasted for at least 8 wks after intervention. Upon comparing the parameters of gait among the three groups at every follow-up visit, no significant difference was observed. Conclusions: Anodal tDCS or physical therapy could be used alone or together as a combination treatment to improve the walking speed of patients with Parkinson disease. The effects lasted for approximately 8 wks. The combination treatment was not superior to the use of tDCS or physical therapy alone. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Moving into poverty during childhood is associated with later sleep problems

A social gradient in sleep has been demonstrated across the life span, but previous studies have been cross-sectional and used self-reported socioeconomic status (SES) indicators. Using registry-based data on family income trajectories, the current study examined the association between relative poverty in childhood and subsequent sleep in adolescence.

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Utility of new-generation pacemakers in sleep apnea screening

Patients with cardiac pacemakers present a high prevalence of undiagnosed sleep apnea syndrome (SAS). New-generation pacemakers have algorithms that identify sleep respiratory events. Our aim was to evaluate their accuracy in the diagnosis of SAS.

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Validation of the screening tool ApneaLink® in comparison to polysomnography for the diagnosis of sleep-disordered breathing in children and adolescents

While out-of-center testing was introduced as an alternative for the diagnosis of obstructive sleep apnea in adults, polysomnography (PSG) is still considered mandatory in the diagnosis of sleep-disordered breathing (SDB) in children. The purpose of this study was to validate the outpatient screening device ApneaLink® in comparison to PSG in children and adolescents for the diagnosis of SDB.

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Relationship between stress coping and sleep disorders among the general Japanese population: a nationwide representative survey

To clarify the prevalence of stress, and examine the relationship between sleep disorders and stress coping strategies among highly stressed individuals in the general Japanese population.

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Relationship between obstructive sleep apnea and neuroimaging signatures of cerebral small vessel disease in community-dwelling older adults. The Atahualpa Project

/Objectives: Evidence of a relationship between obstructive sleep apnea (OSA) and neuroimaging signatures of cerebral small vessel disease (SVD) is limited. The present study aimed to evaluate this association in older adults living in rural Ecuador, where small vessel disease is a major pathogenetic mechanism underlying stroke.

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Post-traumatic headache in patients with minimal traumatic intracranial hemorrhage after traumatic brain injury: a retrospective matched case-control study

No evidence is available on the risks of neurologically asymptomatic minimal traumatic intracranial hemorrhage (mTIH) in patients with traumatic brain injury (TBI) for post-traumatic headache (PTH). The purpos...

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Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know.

Summary: Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Pain Management in Abdominal Wall Reconstruction.

Background: In abdominal wall reconstruction, adequate pain control and minimization of narcotic consumption are essential to improving patient outcomes and satisfaction. Previous studies have examined the role of individual strategies, such as neuraxial analgesia and multimodal analgesia. However, there has not been a study that examined all potential determinants of postoperative narcotic requirements, including intraoperative strategies. Methods: Consecutive patients who underwent abdominal wall reconstruction were reviewed. Preoperative factors (chronic preoperative narcotic usage, indication for abdominal wall reconstruction, administration of neuraxial analgesia), intraoperative factors (intraoperative narcotics administered, method of mesh fixation), and postoperative factors (multimodal analgesia, complications) were collected. The main outcomes were daily amount of opioids used and length of hospital stay. Results: Ninety-three patients were included in the study. Patients who had an epidural required lower doses of opioids postoperatively, while those on chronic preoperative opioids, those whose mesh was fixated using transfascial sutures, and those who received large doses of opioids intraoperatively required higher doses of postoperative opioids. Hospital length of stay was longer in patients who received transfascially sutured mesh and those on chronic opioids preoperatively. Conclusions: This study provides potential strategies to improve pain control and minimize narcotic consumption postoperatively in patients undergoing abdominal wall reconstruction. Intraoperative administration of opioids should be minimized to avoid the development of tolerance. Epidural analgesia reduces postoperative narcotic requirement and may be especially beneficial in patients at highest risk for postoperative pain, including those on chronic opioids, and those in whom transfascial sutures are used for mesh fixation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Using the Venous Pectoral Branch from the Thoracoacromial System as a Lifeboat in Autologous Breast Reconstruction.

Summary: The most common recipient vessels for autologous free flap breast reconstruction are the internal mammary vessels. At times, there are problems with the exposed internal mammary vein (IMV) that require other options such as using the contralateral IMV, superior rib resection to access proximal IMV, retrograde IMV use, and thoracodorsal vein access with or without a vein graft. This case demonstrates using the pectoral branch of the thoracoacromial venous system without a vein graft as a lifeboat option when the IMV is not suitable for anastomosis. C.W. was a 65-year-old female who underwent right-sided mastectomy with placement of a tissue expander. After adjuvant radiation therapy, C.W. underwent deep inferior epigastric perforator free flap breast reconstruction. During exposure of the internal mammary artery and IMV, an iatrogenic venotomy occurred that precluded the use of this vessel as a reliable recipient. The deep inferior epigastric perforator flap pedicle was then dissected proximal to isolate the artery and vein, and the vein was successfully anastomosed to the venous pectoral branch of the thoracoacromial system. The postoperative course was uneventful and patient was discharged home on postoperative day 4. Using the venous pectoral branch of the thoracoacromial is a safe and valuable option that can be considered in difficult situations when the IMV is not a suitable option. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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A Unique Lymphaticovenous Supermicrosurgery Training Curriculum: Reflections on Validation and Competency Thresholds.

Summary: Supermicrosurgery is becoming a commonly used technique in various subspecialties of reconstructive surgery. However, there is a lack of standardization and validation in novel supermicrosurgical training. Current simulation training programs are not adequately focused on the challenges encountered during clinical supermicrosurgery practice. This article describes the authors' experience utilizing a supermicrosurgery competency-based training curriculum, in a simulation-based environment, toward safe clinical practice for lymphatic submillimeter supermicrovascular surgery. This article demonstrates the senior authors' (I.K.) Halstedian competency-based curriculum for lymphaticovenous anastomosis training. Further, a step-by-step training utilizing the chicken thigh and the living rat high fidelity simulation models, which subsequently allows supervised one-to-one clinical training with verified clinical competency outcomes, are demonstrated. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Gender Confirmation Surgery: Cosmetic or Reconstructive Procedure?.

No abstract available

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Unilateral Internal Mammary Recipient Vessels for Bilateral DIEP Flap Breast Reconstruction.

Summary: The deep inferior epigastric perforator flap has become increasingly popular for breast reconstruction with the most common recipient vessels being the internal mammary artery and vein. In certain cases, however, these recipient vessels are inadequate due to an absent or diminutive vein. Moreover, patients at high risk for future coronary artery disease may sacrifice the best conduit for coronary revascularization if the internal mammary recipients are used. Alternative recipient vessels, including the thoracodorsal, thoracoacromial, external jugular, and cephalic vessels have significant limitations. In this report, we describe a novel technique using unilateral internal mammary recipient vessels for bilateral free flap breast reconstruction. Two cases are presented that represent distinct indications for this technique: (1) absence or inadequacy of unilateral recipient vessels and (2) preservation of the left internal mammary system for future bypass in patients at high risk for coronary artery disease. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Spike threshold dynamics in spinal motoneurons during scratching and swimming

Abstract

During functional spinal neural network activity motoneurons receive intense synaptic input, and this could modulate the threshold for action potential generation, providing the ability to dynamically adjust the excitability and recruitment order for functional needs. In the present study we investigated the dynamics of action potential threshold during motor network activity. Intracellular recordings from spinal motoneurons in an ex vivo carapace-spinal cord preparation from adult turtles were performed during two distinct types of motor behaviour – fictive scratching and fictive swimming. We found that the threshold of the first spike in episodes of scratching and swimming was the lowest. The threshold potential depolarizes by about 10 mV within each burst of spikes generated during scratch and swim network activity and recovers between bursts to a slightly depolarized level. Depolarization of the threshold potential results in decreased excitability of motoneurons. Synaptic inputs do not modulate the threshold of the first action potential during episodes of scratching or of swimming. There is no correlation between changes in spike threshold and interspike intervals within bursts. Slow synaptic integration that results in a wave of membrane potential depolarization rather than fast synaptic events preceding each spike is the factor influencing the threshold potential within firing bursts during motor behaviours.

This article is protected by copyright. All rights reserved

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Angiotensin 1-7 inhibits angiotensin II-stimulated head and neck cancer progression

Angiotensin II (Ang II) is the product of the proteolytic action of angiotensin-converting enzyme (ACE) on the precursor peptide, angiotensin I (Ang I). In addition to its vasoactive properties, Ang II is able to stimulate angiogenesis and act as a mitogen, promoting cellular proliferation. Recently, evidence has emerged that Ang II is also able to promote tumour invasion, a key step in the metastatic cascade, although the mechanisms by which it does so remain largely obscure. Here we show that Ang II is able to promote the invasion and migration of head and neck squamous cell carcinoma (HNSCC) cells both in an autocrine manner and by triggering stromal tumour-paracrine interactions. The effects of Ang II on autocrine and paracrine signalling pathways are mediated by angiotensin receptor 1 (AT₁R) and inhibited by angiotensin 1-7 (Ang 1-7), a peptide produced from Ang II by the action of angiotensin-converting enzyme 2 (ACE2). These data are the first to demonstrate a role for the renin–angiotensin system in oral carcinogenesis and raise the possibility of utilizing AT₁R receptor antagonists and/or Ang 1-7 as novel therapeutic agents for HNSCC.

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Oral problems and quality of life of preschool children: self-reports of children and perception of parents/caregivers

The purpose of this study was to evaluate the association between oral health problems and oral health-related quality of life (OHRQoL) of preschool children according to both self-reports and the reports of parents/caregivers. A school-based, cross-sectional study was conducted with 769 preschool children and their parents/caregivers. The OHRQoL was evaluated using the Scale of Oral Health Outcomes for Five-Year-Old Children (SOHO-5). Based on logistic regression for complex samples, the following variables were found to be associated with poorer OHRQoL in the parent/caregiver version: toothache (OR = 6.77; 95% CI: 3.95–11.59); consequences of untreated dental caries (OR = 2.69; 95% CI: 1.27–5.70); and anterior open bite (OR = 2.01; 95% CI: 1.13–3.56). The following variables were associated with poorer OHRQoL in the child self-report version: toothache (OR = 3.34; 95% CI: 2.11–5.29); cavitated lesions (anterior teeth) (OR = 2.20; 95% CI: 1.26–3.84); occurrence of traumatic dental injury (OR = 1.77; 95% CI: 1.19–2.61); and anterior open bite (OR = 1.95; 95% CI: 1.16–3.29). We conclude that children with dental caries (or its sequelae) had poorer OHRQoL. Having experienced a traumatic dental injury and having a malocclusion were also associated with a poorer OHRQoL.

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Antibiotic-prescribing habits among Norwegian dentists: a survey over 25 years (1990–2015)

Bacterial antibiotic resistance is a steadily growing global problem, which today is compared with issues such as global warming, ozone depletion, and extinction of species. Consequently, calls come from global, Pan-European, and national authorities to gain insight into, limit, and stringently qualify the use of antibiotics in human and veterinary medicine, as well as in food production. Dentists are not considered to be frequent prescribers of antibiotics. However, few studies have identified how much, and in which situations, dentists prescribe such drugs. The aims of the present study were to survey Norwegian dentists’ antibiotic-prescribing habits in 2015 and to compare the findings with previous studies (1990 and 2004) and with the actual numbers of dispensed prescriptions obtained from the ‘Norwegian National Prescription Register’. The results from 1990 to 2004 show that there was a general increase in antibiotic prescriptions by Norwegian dentists, followed by a reduction or flattening of the prescription volume curve from 2004 to 2015. Despite this, possibilities for further improvements have been identified and recommendations given for targeted campaigns to reduce the prescription volume in dentistry by a further 30%, which has been ordered by the Norwegian National Assembly.

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Treatment of laryngopharyngeal reflux using a sleep positioning device: A prospective cohort study

Laryngopharyngeal reflux (LPR) symptoms are often resistant to management and cause significant quality of life impairment to patients with this disease. This study assesses the utility of a sleep-positioning device (SPD) in treating LPR.

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Lateral cervical approach for supracricoid partial laryngectomy

The supracricoid partial laryngectomy has been described for the treatment of T3 laryngeal glottic and supraglottic tumors as well as upfront and salvage surgery. Good oncological and functional outcomes are expected, while the post-operative rehabilitation can be quite difficult for the patient. Early and late complications can occur especially in salvage surgery. Neck dissection according to the T stage is often associated with the resection of the primary tumor.

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An amazing cause of false pet positivity: Diagnosed after a lung cancer surgery

Abstract

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has an effective role in both diagnosis and management of patients with lung cancer. There are many reasons could cause false positivity on PET/CT.A 60-year-old man was admitted a mass on thorax CT and diagnosed as squamous cell carcinoma. Lobectomy with lymph node dissection was performed after evaluation of distant metastases. There were pathological lymph nodes detected on PET/CT at six month following period. Endobronchial ultrasonography guided transbronchial needle aspiration was performed for differantial diagnosis. The pathologic diagnosis was granuloma which developed in response to suture material. We interpreted this granulomatous reaction as gossypiboma which developed against long-left or forgotten suture material. In conclusion, based on this case, gossypiboma (or granulomatous inflammation in response to foreign bodies) should be also considered in differential diagnosis of intrathoracic lymph nodes with PET positivity in a previously operated patient.

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Current Controversies on Wernicke’s Area and its Role in Language

Abstract

Purpose of Review

The aim of the study is to assess historical anatomical and functional definitions of Wernicke’s area in light of modern lesion and neuroimaging data.

Recent Findings

“Wernicke’s area” has become an anatomical label usually applied to the left posterior superior temporal gyrus and adjacent supramarginal gyrus. Recent evidence shows that this region is not critical for speech perception or for word comprehension. Rather, it supports retrieval of phonological forms (mental representations of phoneme sequences), which are used for speech output and short-term memory tasks. Focal damage to this region produces phonemic paraphasia without impairing word comprehension, i.e., conduction aphasia. Neuroimaging studies in recent decades provide evidence for a widely distributed temporal, parietal, and frontal network supporting language comprehension, which does not include the anatomically defined Wernicke area.

Summary

The term Wernicke’s area, if used at all, should not be used to refer to a zone critical for speech comprehension.

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Barcelona Clinic Liver Cancer (BCLC) Staging: Does It Cover All Our Expectation

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Neuroendocrine Tumors of the Esophagus: State of the Art in Diagnostic and Therapeutic Management

Abstract

Introduction

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms composed of cells containing dense-core neuroendocrine secretory granules in their cytoplasm. NETs of the esophagus are exceedingly uncommon, with a parallel absence of data published on clinical features, prognosis, and proposed treatment strategies.

Methods

As relevant classification is not well-established, knowledge acquired in NETs of lung and gastrointestinal sites usually guides esophageal NET management. Associated subtypes are divided based upon shared neuroendocrine features into small and large cell NET, typical and atypical carcinoid.

Results

Common presenting symptoms include dysphagia, abdominal discomfort, weight loss, melena, and on occasion, signs of carcinoid syndrome. Endoscopic findings describe a polypoid, nodular elevated lesion with an overlying surface depicted as mostly smooth and glistening. Disease metastasis is assessed using anatomical imaging, including computed tomography (CT), endoscopic ultrasonography (EUS), and positron emission tomography (PET)-CT. Prognosis is influenced by the extent of lymph node metastasis and potential lymphovascular invasion. Furthermore, proliferative activity, estimated using mitotic count or Ki-67 immunostaining, has been suggested as a significant prognostic parameter.

Conclusion

Therapeutic approach depends on clinical staging. Nevertheless, currently, a specific treatment algorithm for esophageal NETs has not been elucidated. Endoscopic resection has been proposed in NETs less than 1 cm in size with absence of regional lymph node metastasis, while surgical excision combined with adjuvant chemotherapy remains the treatment of choice.

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Is there an advantage in onset of action with mixing lignocaine and bupivacaine?

Ever since Lidocaine (lignocaine) was first synthesised in 1943 and Bupivacaine first synthesised in 1957, surgeons have been mixing these two local anaesthetics. Lidocaine with its shorter duration of action has been linked (inaccurately) with a more rapid onset of action while the longer duration of Bupivacaine has again been suggested to have a slower onset of action. This erroneous extrapolation has led to many mixing the two to have an anaesthetic solution which might have rapid onset and long duration.

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IgG3 Subclass: a possible trigger of mixed cryoglobulin cascade in hepatitis C virus chronic infection

HCV is a hepatotropic and lymphotropic virus and is the most frequent cause of "benign" mono-oligoclonal B-lymphocyte proliferation, observed in mixed cryoglobulinemia (MC). The study aims to investigate the presence, prevalence and characteristics of the subclasses of cryoglobulins in HCV-patients to look for a relationship with MC. Fifty HCV-infected patients with cryoglobulins were enrolled. IgG subclasses were characterized in cryoprecipitate, and serum IgG and IgM Rheumatoid Factor (RF) were determined.

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Optimized DNA Vaccine Enhanced by Adjuvant IL28B Induces Protective Immune Responses Against Herpes Simplex Virus Type 2 in Mice

Viral Immunology , Vol. 0, No. 0.


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Multidrug-Resistant Enterobacteriaceae in Lebanese Hospital Wastewater: Implication in the One Health Concept

Microbial Drug Resistance , Vol. 0, No. 0.


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Coordinated Expression of acrAB-tolC and Eight Other Functional Efflux Pumps Through Activating ramA and marA in Salmonella enterica serovar Typhimurium

Microbial Drug Resistance , Vol. 0, No. 0.


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Healthy Bovines as Reservoirs of Major Pathogenic Lineages of Staphylococcus aureus in Portugal

Microbial Drug Resistance , Vol. 0, No. 0.


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Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Susceptibility to Dengue Virus Infection in a Mexican Population

Viral Immunology , Vol. 0, No. 0.


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Descendens vagohypoglossi: rare variant of the superior root of ansa cervicalis

Knowledge of variants in the formation and position of the ansa cervicalis is important in head and neck surgery, specifically in reconstructions of the tongue that use the infrahyoid muscles, and in the anastomosis of the ansa cervicalis to the recurrent laryngeal nerve when the laryngeal muscles have been paralysed. We describe a rare variant of the superior root of the ansa cervicalis, which had a contribution from the vagus and hypoglossal nerves. The inferior root was formed by the C2 and C3 ventral rami, but it passed medial to the internal jugular vein before it joined the superior root to form the loop.

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Panton-Valentine leukocidin-producing Staphylococcus aureus infection of the neck that mimicked disseminated malignancy

A 50-year-old man presented to the emergency department of a teaching hospital in the UK with a midline swelling of the neck, chest pain, and fever. The swelling had been incised at another hospital two weeks previously, but after initial improvement it had increased in size and become more inflamed. He was taking flucloxacillin and phenoxymethylpenicillin prescribed by a general practitioner. His medical history included repair of a patent ductus arteriosus as a child. His temperature was 38.6°C and oxygen saturation 95% on air.

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Seven-year review of dental foundation year 2/senior house officer training at the Oral and Maxillofacial Surgery Unit in Oxford

The dental senior house officer (SHO)/dental foundation year 2 (DF2) posts in Oxford have provided hospital-based training for dentists, but in 2013 the Oral and Maxillofacial Surgery (OMFS) Unit withdrew from DF2 training because persistent negative feedback from the dental deanery varied from that obtained internally. We sent questionnaires to a consecutive group of 62 dentists who had worked at the John Radcliffe Hospital, Oxford, between 2006 and 2013 to find out about their experience of the posts.

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Guided bone regeneration at zirconia and titanium dental implants: a pilot histological investigation

Abstract

Aim

To test whether guided bone regeneration (GBR) of peri-implant defects at zirconia (ZrO₂) implants differs from GBR at titanium (Ti) implants regarding the bone integration of the implant and of the grafting material.

Materials and methods

Maxillary premolars and molars were extracted in seven dogs. After 5 months, four semi-saddle bone defects were created in each maxilla. Implant placement and simultaneous GBR were performed using the following randomly assigned modalities: (1) ZrO₂ implant + deproteinized bovine bone mineral (DBBM) granules + a collagen membrane (CM), (2) ZrO₂ implant + DBBM with 10% collagen matrix + CM, (3) ZrO₂ implant + DBBM block + CM, and (4) Ti implant + DBBM granules + CM. After 3 months, one central histological section of each site was prepared. Histomorphometrical assessments were performed evaluating the augmented area (AA) within the former bone defect (primary outcome), the area of new bone (NB), bone substitute (BS), and non-mineralized tissue (NMT) within AA in mm². In addition, the distance between the most coronal bone-to-implant contact and the margin of the former bone defect (fBIC-DEF), and the bone-to-implant contact fraction (BIC) were measured in mm.

Results

AA measured 8.6 ± 4.0 mm² for ZrO₂ implant + DBBM granules, 4.7 ± 1.6 mm² for ZrO₂ implant + DBBM-collagen, 5.1 ± 1.9 mm² for ZrO₂ implant + DBBM block, and 7.6 ± 2.8 mm² for Ti implant + DBBM granules. There were no statistically significant differences between the treatment modalities (P > 0.05). NB reached 2.0 ± 1.7 mm² for ZrO₂ implant + DBBM granules, 0.9 ± 0.9 mm² for ZrO₂ implant + DBBM-collagen, 2.1 ± 0.9 mm² for ZrO₂ implant + DBBM block, and 0.8 ± 0.6 mm² for Ti implant + DBBM granules. fBIC-DEF amounted to 2.1 ± 1.7 mm² for ZrO₂ implant + DBBM granules, to 2.7 ± 1.1 mm² for ZrO₂ implant + DBBM-collagen, to 2.9 ± 1.2 mm² for ZrO₂ implant + DBBM block, and to 3.4 ± 0.4 mm² for Ti implant + DBBM granules. BIC measured 70 ± 19% for ZrO₂ implant + DBBM granules, 69 ± 22% for ZrO₂ implant + DBBM-collagen, 77 ± 30% for ZrO₂ implant + DBBM block, and 66 ± 27% for Ti implant + DBBM granules.

Conclusions

The findings of the present pilot study suggest that zirconia and titanium implants grafted with DBBM granules and covered with a collagen membrane do not perform differently regarding the augmented ridge contour, the NB formation, and the implant osseointegration.

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Parinaud syndrome: Any clinicoradiological correlation?

Introduction

The significance of MRI findings of patients with Parinaud syndrome (PS) with respect to clinical characteristics is poorly defined. Over the past decades, all patients with PS undergo magnetic resonance imaging which allows a better identification of the lesion localization. We compared the neuro-ophthalmological findings of patients with PS caused by intrinsic (intra-axial) vs extrinsic (pineal gland tumor) brainstem lesions.

Methods

Medical records of patients with PS evaluated between 2000 and 2016 were retrospectively reviewed.

Results

Twenty-six patients with PS were included. Eight patients had pineal gland tumors and hydrocephalus. Two patients had hydrocephalus due to aqueduct stenosis and fourth ventricle tumor. Sixteen patients suffered from an intrinsic brainstem lesion and seven associated with hydrocephalus.

The neuro-ophthalmological findings did not differ between patients with extrinsic and intrinsic brainstem lesions. No correlation was found between the grade of hydrocephalus and number of clinical findings except for more findings in low-grade hydrocephalus in intrinsic (40%) vs extrinsic (0%) lesions (P=.003). Patients with moderate brainstem lesions and hydrocephalus had more clinical findings (65%) than patients with the same grade of brainstem involvement without hydrocephalus (29%) (P=.03). The resolution rate of ophthalmological findings was comparable in all groups of patients.

Conclusions

Our results did not show differences in neuro-ophthalmological findings between intra- and extra-axial lesions causing PS. However, the presence of hydrocephalus was an important factor influencing clinical findings. The prognosis of PS was less favorable than generally reported.

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Association between Parkinson's disease and diabetes: Data from NEDICES study

Background

Despite growing evidence showing an association between Parkinson's disease (PD) and diabetes, epidemiological studies have shown conflicting results.

Aims of the study

To evaluate the association between PD and diabetes and the impact of diabetes duration in this association in an elderly (≥65 years) Spanish population.

Methods

Data for this cross-sectional population-based analysis were obtained from NEDICES study. Subjects were identified from census list. Diagnosis of PD was confirmed by neurological examination. Diabetes was defined by self-report, being on antidiabetic medication or diagnosis on medical records. Logistic regression analysis adjusted by potential confounders was performed to estimate the association between both conditions and also after dividing patients into short-duration (<10 years) and long-duration (≥10 years) diabetes.

Results

A total of 4998 subjects were included (79 PD and 4919 controls). Univariate analysis did not show any association between prevalence of PD and diabetes (OR 1.89, 95% CI 0.90-3.98, P=.09), although subgroup analysis showed a positive association in those with long-duration diabetes (3.27, 95% CI 1.21-8.85, P=.02).

Conclusions

Diabetes duration might be an important factor in the association between PD and diabetes, and the risk might be limited to those with longer disease duration.

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Names and phenotypes of CD163 positive macrophages in oral precancerous lesions

We are quite interested in the recently published article entitled “Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: Implications for patients with oral precancerous lesions” [1]. The authors had explored the PD-L1 expression in the stoma cells in oral precancerous lesions and investigated the relationships among PD-L1 positive cells and malignant transformation of these cells. We have two questions on this article.

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Ocular vestibular evoked myogenic potential in patients with myasthenia gravis

Myasthenia gravis (MG) is an archetypic disorder of neuromuscular junctions (NMJs) and autoantibody-mediated disease causing fatigable weakness of skeletal muscles with an ocular onset in up to 85%. The aim of this study was to detect extra ocular muscles (EOMs) abnormalities in MG patients using ocular vestibular evoked myogenic potential (oVEMP) n10 response.

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Prospective analysis of 231 elective neck dissections in oral squamous cell carcinoma with node negative neck—To decide the extent of neck dissection

To evaluate the incidence of level IIB and IV lymph node metastases in patients of oral carcinoma with N0 necks. This study will help to decide the extent and need of routine comprehensive removal of these specific lymph node groups in selective neck dissection.

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Characterization of Chronic Axonal Degeneration Using Diffusion Tensor Imaging in Canine Spinal Cord Injury: A Quantitative Analysis of Diffusion Tensor Imaging Parameters According to Histopathological Differences

Journal of Neurotrauma , Vol. 0, No. 0.


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Impact of Therapy on Recovery during Rehabilitation in Patients with Traumatic Spinal Cord Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Names and phenotypes of CD163 positive macrophages in oral precancerous lesions

We are quite interested in the recently published article entitled “Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: Implications for patients with oral precancerous lesions” [1]. The authors had explored the PD-L1 expression in the stoma cells in oral precancerous lesions and investigated the relationships among PD-L1 positive cells and malignant transformation of these cells. We have two questions on this article.

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Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb

Future Oncology Ahead of Print.


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Letter in reply: Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases

Future Oncology Ahead of Print.


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Robotic-assisted radical cystectomy versus open radical cystectomy for management of bladder cancer: review of literature and randomized trials

Future Oncology Ahead of Print.


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Highlights of the San Antonio Breast Cancer Symposium 2016

Future Oncology Ahead of Print.


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Re: Gaskill CS, Awan JA, Watts CR, Awan SN. Acoustic and perceptual classification of within-sample normal, intermittently dysphonic, and consistently dysphonic voice types. J Voice. 2016;31:218–228

The recently published study of Gaskill et al constitutes a remarkable contribution to the understanding of time-variance of dysphonic voice quality, because time-variance is often neglected in the description of voice quality. This circumstance may cause problems in clinical voice quality evaluation. We acknowledge the authors' contributions to clarify the different semantic levels of voice quality description, which are the speech level, the segmental level, the signal frame level, and the level of cycles.

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Characterization of Chronic Axonal Degeneration Using Diffusion Tensor Imaging in Canine Spinal Cord Injury: A Quantitative Analysis of Diffusion Tensor Imaging Parameters According to Histopathological Differences

Journal of Neurotrauma , Vol. 0, No. 0.


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Impact of Therapy on Recovery during Rehabilitation in Patients with Traumatic Spinal Cord Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Upper-airway flow limitation and transcutaneous carbon dioxide during sleep in normal pregnancy

Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Ville Rimpilä, Riina Jernman, Katariina Lassila, Jukka Uotila, Heini Huhtala, Johanna Mäenpää, Olli Polo
ObjectiveSleep during pregnancy involves a physiological challenge to provide sufficient gas exchange to the fetus. Enhanced ventilatory responses to hypercapnia and hypoxia may protect from deficient gas exchange, but sleep-disordered breathing (SDB) may predispose to adverse events. The aim of this study was to analyze sleep and breathing in healthy pregnant women compared to non-pregnant controls, with a focus on CO2 changes and upper-airway flow limitation.MethodsHealthy women in the third trimester and healthy non-pregnant women with normal body mass index (BMI) were recruited for polysomnography. Conventional analysis of sleep and breathing was performed. Transcutaneous carbon dioxide (TcCO2) was determined for each sleep stage. Flow-limitation was analyzed using the flattening index and TcCO2 values were recorded for every inspiration.ResultsEighteen pregnant women and 12 controls were studied. Pregnancy was associated with shorter sleep duration and more superficial sleep. Apnea–hypopnea index, arterial oxyhemoglobin desaturation, flow-limitation, snoring or periodic leg movements were similar in the two groups. Mean SaO2 and minimum SaO2 were lower and average heart rate was higher in the pregnant group. TcCO2 levels did not differ between groups but variance of TcCO2 was smaller in pregnant women during non-rapid eye movement (NREM). TcCO2 profiles showed transient TcCO2 peaks, which seem specific to pregnancy.ConclusionsHealthy pregnancy does not predispose to SDB. Enhanced ventilatory control manifests as narrowing threshold of TcCO2 between wakefulness and sleep. Pregnant women have a tendency for rapid CO2 increases during sleep which might have harmful consequences if not properly compensated.



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Predictors of sleep disturbances in the first year of life: a longitudinal study

Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Stefania Sette, Emma Baumgartner, Raffaele Ferri, Oliviero Bruni
ObjectiveThe aim of this study was to identify early predictors of nocturnal awakenings and short sleep duration during the first year of life, in terms of sleep habits and patterns. We also analyzed the trend of nocturnal awakenings and total sleep duration from 3 to 12 months of age.MethodsThe parents of 704 infants (49.3% female) were interviewed during their first year of life. The interview included questions on infant sleep (eg, sleep habits, sleep duration, number of nocturnal awakenings) and maternal perception of infant sleep difficulties.ResultsThe study results indicate that most of the infants at risk, with three or more nocturnal awakenings or ≤10 h of total sleep duration in the early months of life, tend to display a similar pattern of sleep problems at 12 months. The main early predictors of sleep problems at 12 months were sleep duration, sleep initiation method, and nocturnal awakenings. More specifically, infants with three or more nocturnal awakenings or ≤10 h of total sleep duration at 12 months were those with a higher number of awakenings during the night and a shorter sleep duration, at both three and six months. In addition, infants at risk for sleep problems at 12 months had an independent sleep initiation method at three months, whereas these same infants had a nonindependent sleep initiation method at six months.ConclusionsOur study identified the early predictors of sleep problems at 12 months. Caregivers should identify these early symptoms in infants to prevent possible sleep difficulties in later years.



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Overlap Parasomnia Disorder in a case of Creutzfeldt-Jakob Disease

Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Monica Puligheddu, Patrizia Congiu, Ilaria Laccu, Michela Figorilli, Gioia Gioi, Lorenzo Polizzi, Patrizia Pisanu, F. Marrosu, Federica Provini




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Descendens vagohypoglossi: rare variant of the superior root of ansa cervicalis

Publication date: Available online 26 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): S. Nayak B., P. Shetty, D. R., A. Aithal P., N. Kumar
Knowledge of variants in the formation and position of the ansa cervicalis is important in head and neck surgery, specifically in reconstructions of the tongue that use the infrahyoid muscles, and in the anastomosis of the ansa cervicalis to the recurrent laryngeal nerve when the laryngeal muscles have been paralysed. We describe a rare variant of the superior root of the ansa cervicalis, which had a contribution from the vagus and hypoglossal nerves. The inferior root was formed by the C2 and C3 ventral rami, but it passed medial to the internal jugular vein before it joined the superior root to form the loop.



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Panton-Valentine leukocidin-producing Staphylococcus aureus infection of the neck that mimicked disseminated malignancy

Publication date: Available online 26 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Little, N. Renny




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Seven-year review of dental foundation year 2/senior house officer training at the Oral and Maxillofacial Surgery Unit in Oxford

Publication date: Available online 26 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Garg, L. Wong, D. Dhariwal
The dental senior house officer (SHO)/dental foundation year 2 (DF2) posts in Oxford have provided hospital-based training for dentists, but in 2013 the Oral and Maxillofacial Surgery (OMFS) Unit withdrew from DF2 training because persistent negative feedback from the dental deanery varied from that obtained internally. We sent questionnaires to a consecutive group of 62 dentists who had worked at the John Radcliffe Hospital, Oxford, between 2006 and 2013 to find out about their experience of the posts. Forty responded (65% response rate). We analysed their expectations, the support provided, their experience of teaching and training, the opportunities available, and free-text feedback about the post and their current posts. They had all found the job helpful, and had gained generic, dental, medical, and surgical skills. The overall mean (SD) score for the post was 8 (2) on a Likert scale of 1-10 (with 10 being excellent). When they completed the questionnaire between December 2013 and July 2014, 18 respondents were working as general dental practitioners and four were training for a career in OMFS. The study showed that work as a dental SHO or DF2 has multiple benefits. We hope that our findings will help to improve OMFS training posts for dental core trainees in Oxford.



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President’s Message

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Clinical Pathways: Recommendations for Putting Patients at the Center of Value-Based Care

Two major trends that have been affecting the provision of oncology care in the United States are a shift from volume-based to value-based care and a push toward patient-centered healthcare. However, these two trends are not always completely aligned with each other. Value-based payment models, including clinical pathways, are one strategy being implemented by oncology stakeholders to help encourage the uptake of value-based oncology care. If structured with the patient in mind, they can improve quality of care for patients with cancer, decrease inappropriate care while enabling appropriate personalization of care, and constrain rising prices by demanding a stronger link between cost and value. If not structured appropriately, they can limit patient choice, impede access to innovative treatments, and encourage one-size-fits-all oncology care. Clin Cancer Res; 23(16); 1–5. ©2017 AACR.

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Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation

Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the e...

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Glycerol-3-phosphate acyltransferase 1 promotes tumor cell migration and poor survival in ovarian carcinoma

Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth.

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SPIN90 depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression

Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. Spin90 deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. Spin90 depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development.

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Hypoxia-induced downregulation of DUSP-2 phosphatase drives colon cancer stemness

Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of cyclooxygenase-2 (COX-2)-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2-induced tumor growth and cancer stemness. Genome-wide profile analysis revealed that genes regulated by DUSP2 were similar to those controlled by histone deacetylase. Indeed, treatment with novel histone deacetylase inhibitors abolished hypoxia-induced DUSP2 downregulation, COX-2 overexpression, cancer stemness, tumor growth, and drug resistance. Our findings illuminate mechanisms of cancer stemness and suggest new cancer therapy regimens.

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Identification of interacting stromal axes in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a molecularly heterogeneous cancer that is difficult to treat. Despite the role it may play in tumor progression and response to therapy, microenvironmental (stromal) heterogeneity in TNBC has not been well characterized. To address this challenge, we investigated the transcriptome of tumor-associated stroma isolated from TNBC (n=57). We identified four stromal axes enriched for T cells (T), B cells (B), epithelial markers (E), or desmoplasia (D). Our analysis method (STROMA4) assigns a score along each stromal axis for each patient, and then combined the axis scores to subtype patients. Analysis of these subtypes revealed that prognostic capacity of the B, T and E scores was governed by the D score. When compared to a previously published TNBC subtyping scheme, the STROMA4 method better captured tumor heterogeneity and predicted patient benefit from therapy with increased sensitivity. This approach produces a simple ontology that captures TNBC heterogeneity and informs how tumor-associated properties interact to affect prognosis.

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Posttranscriptional upregulation of IDH1 by HuR establishes a powerful survival phenotype in pancreatic cancer cells

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDA). Glucose or glutamine withdrawal resulted in a 5-10-fold protective effect with chemotherapy treatment. PDA xenografts were less sensitive to gemcitabine in hypoglycemic mice compared to hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n=107) with elevated serum glucose levels (HgbA1C>6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDA cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDA cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDA cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR-IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer. <br /> <p> 

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WEE1 kinase inhibitor AZD1775 has pre-clinical efficacy in LKB1-deficient non-small cell lung cancer

G1/S checkpoint loss contributes to carcinogenesis and increases reliance upon the G2/M checkpoint for adaptation to stress and DNA repair, making G2/M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G2/M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several pre-clinical tumor models, often in the molecular context of TP53 loss. Whether AZD1775 efficacy is modulated by other molecular contexts remains poorly understood. The tumor suppressor serine/threonine kinase 11 (LKB1/STK11) is one of the most frequently mutated genes in non-small cell lung cancer (NSCLC) and is commonly co-mutated with oncogenic KRAS mutations. We investigated the pre-clinical effects of AZD1775 in the context of KRAS/LKB1 in NSCLC. Using NSCLC cell lines, we found that AZD1775 alone and in combination with DNA-damaging agents (e.g., cisplatin and radiation) decreased tumor cell viability in LKB1-deficient NSCLC cells. In vitro, LKB1 deficiency enhanced DNA damage and apoptosis in response to AZD1775 exposure compared with wildtype LKB1 cells. In a genetically engineered mouse model of mutant Kras with concomitant loss of Lkb1, combined AZD1775 and cisplatin extended overall survival compared to cisplatin alone. Our data suggest that lack of phosphorylation of LKB1 by ATM was involved in AZD1775-mediated cytotoxicity. Collectively, these findings provide a clinical application for AZD1775 with DNA-damaging agents in KRAS/LKB1 NSCLC.

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GLI1 blockade potentiates the antitumor activity of PI3K antagonists in lung squamous cell carcinoma

Lung squamous cell carcinoma (SCC), strongly associated with smoking, is treated primarily with traditional cytotoxic chemotherapy due to a lack of FDA-approved targeted agents available. Here we identify the Hedgehog pathway transcription factor GLI1 as a critical driver of lung SCC. Analysis of human lung cancer datasets showed that GLI1 mRNA was highly expressed in human lung SCC and portended a poor prognosis. Inhibition of GLI1 in human lung SCC cell lines suppressed tumor cell clonogenicity and proliferation in culture and in vivo. Addition of SHH ligand, SMO antagonists, or other Hedgehog pathway agonists did not affect GLI1 expression in lung SCC cells. However, GLI1 expression was modulated by either inhibition or activation of the PI3K and MAPK pathways. Furthermore, in vivo growth of SCC harboring amplifications of the PI3K gene PIK3CA was attenuated by antagonizing GLI1 and PI3K. Thus, a combinatorial therapeutic strategy that targets the PI3K-mTOR pathway and GLI1 may lead to effective outcomes for PI3K pathway-dependent cancers, in contrast to recent results of human trials with single-agent PI3K antagonists.

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MAPK signaling and inflammation link melanoma phenotype switching to induction of CD73 during immunotherapy

Evolution of tumor cell phenotypes promotes heterogeneity and therapy resistance. Here we found that induction of CD73, the enzyme that generates immunosuppressive adenosine, is linked to melanoma phenotype switching. Activating MAPK mutations and growth factors drove CD73 expression, which marked both nascent and full activation of a mesenchymal-like melanoma cell state program. Proinflammatory cytokines like TNF-alpha cooperated with MAPK signaling through the c-Jun/AP-1 transcription factor complex to activate CD73 transcription by binding to an intronic enhancer. In a mouse model of T cell immunotherapy, CD73 was induced in relapse melanomas, which acquired a mesenchymal-like phenotype. We also detected CD73 upregulation in melanoma patients progressing under adoptive T cell transfer or immune checkpoint blockade, arguing for an adaptive resistance mechanism. Our work substantiates CD73 as target to combine with current immunotherapies, but its dynamic regulation suggests limited value of CD73 pre-treatment expression as a biomarker to stratify melanoma patients.

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Unpaired extracellular cysteine mutations of CSF3R mediate gain or loss of function

Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g. T618I), functionally defective mutations in the extracellular domain of the granulocyte colony-stimulating factor receptor (CSF3R) have been reported only in severe congenital and idiopathic neutropenia patients. Here we describe the first activating mutation in the fibronectin like type III domain of the extracellular region of CSF3R (W341C) in a leukemia patient. This mutation transformed cells via cysteine-mediated intermolecular disulfide bonds, leading to receptor dimerization. Interestingly, a CSF3R cytoplasmic truncation mutation (W791X) found on the same allele as the extracellular mutation and the expansion of the compound mutation was associated with increased leukocytosis and disease progression of the patient. Notably, the primary patient sample and cells transformed by W341C and W341C/W791X exhibited sensitivity to JAK inhibitors. We further showed that disruption of original cysteine pairs in the CSF3R extracellular domain resulted in either gain- or loss-of-function changes, part of which was attributable to cysteine-mediated dimer formation. This, therefore, represents the first characterization of unpaired cysteines that mediate both gain and loss of function phenotypes. Overall, our results show the structural and functional importance of conserved extracellular cysteine pairs in CSF3R and suggest the necessity for broader screening of CSF3R extracellular domain in leukemia patients.

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Targeting adenosine in BRAF-mutant melanoma reduces tumor growth and metastasis

Increasing evidence exists for the role of immunosuppressive adenosine in promoting tumor growth and spread in a number of cancer types, resulting in poor clinical outcomes. In this study, we assessed whether the CD73-adenosinergic pathway is active in melanoma patients and whether adenosine restricts the efficacy of clinically approved targeted therapies for commonly mutated BRAFV600E melanoma. In AJCC Stage III melanoma patients, CD73 expression (the enzyme that generates adenosine) correlated significantly with patients presenting nodal metastatic melanoma, suggesting that targeting this pathway may be effective in advanced stage disease. In addition, dabrafenib and trametinib treatment of CD73+ BRAFV600E-mutated melanomas caused profound CD73 downregulation in tumor cells. Inhibition of BRAF and MEK in combination with the A2A adenosine receptor (A2AR) provided significant protection against tumor initiation and metastasis formation in mice. Our results suggest that targeting adenosine may enhance therapeutic responses for melanoma patients receiving targeted or immune-based therapies.

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A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling

A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling

Oncogenesis 6, e350 (June 2017). doi:10.1038/oncsis.2017.51

Authors: H Muranaka, A Hayashi, K Minami, S Kitajima, S Kohno, Y Nishimoto, N Nagatani, M Suzuki, L A N Kulathunga, N Sasaki, N Okada, T Matsuzaka, H Shimano, H Tada & C Takahashi

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Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model

Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model

Oncogenesis 6, e351 (June 2017). doi:10.1038/oncsis.2017.52

Authors: Y Yang, Q Liu, J Lu, D Adah, S Yu, S Zhao, Y Yao, L Qin, L Qin & X Chen

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Breast Implant Techniques Vary Widely Around the World

From country to country, breast implant surgeries tend to vary widely in technique, as well as in type and size of implant, according to an international survey of surgeons.
Reuters Health Information

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Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

Abstract

One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing–remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early long-term treatment with fingolimod (1 mg/kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in WAG/Rij rats. However, these effects were transitory, as 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control levels. Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced phosphorylated mammalian target of rapamycin and phosphorylated p70S6k levels, and by increased phosphorylated Akt in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic effects of fingolimod. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of lysine 8 of histone H4 (at both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects of fingolimod. However, the antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.

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Therapeutic Targets for Multiple Sclerosis: Current Treatment Goals and Future Directions

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing–remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity. This review will describe the most common treatment goals in MS: the Rio scores, disease-free survival, and no evidence of disease activity. We will also cover how well current disease-modifying therapies achieve no evidence of disease activity, and discuss future options for improving MS treatment targets.

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Validation of the graded prognostic assessment for lung cancer with brain metastases using molecular markers (lung-molGPA)

Many patients with brain metastases from non-small cell lung cancer have limited survival, while others survive for several years, depending on patterns of spread, EGFR and ALK alterations, among others. The p...

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Dosimetric evaluation of synthetic CT for magnetic resonance-only based radiotherapy planning of lung cancer

Interest in MR-only treatment planning for radiation therapy is growing rapidly with the emergence of integrated MRI/linear accelerator technology. The purpose of this study was to evaluate the feasibility of ...

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The Safety and Effectiveness of Superficial Cervical Plexus Block in Oral and Maxillofacial Surgery as an Alternative to General Anesthesia in Selective Cases: A Clinical Study

Abstract

Aim

To assess the safety and effectiveness of superficial cervical plexus (SCP) block in oral and maxillofacial surgical (OMFS) practice as an alternative to general anesthesia in selective cases.

Subjects and Methods

The total number of patients was 10, out of which 6 were male and 4 were female patients. Five patients had incision and drainage of perimandibular space infections, two patients had enucleation of cyst in the body of mandible, one patient had open reduction and internal fixation isolated angle fracture, and two patients had submandibular lymph node biopsies. Informed & written consent were obtained from the patients after they had the procedure explained to them. Medically compromised patients and those who were excessively anxious and apprehensive, patient who did not want the procedure to be done under regional anesthesia, and patients with a history of allergy to local anesthetic were excluded. All patients had their surgical procedures under regional anesthesia (SCP block with supplemental nerve blocks) performed by the same surgeon under the supervision of anesthesiologist with continuous monitoring.

Results

SCP block with concomitant mandibular nerve and long buccal nerve block has a high success rate, low complication rate, and high patient acceptability as shown in the study.

Conclusion

Superficial cervical plexus block anesthesia is a safe and useful anesthetic technique with the low risk of accidents and complications, thus a good alternative for regional anesthesia in selected cases in oral and maxillofacial surgery.

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Clozapine as a Model for Antipsychotic Development

Abstract

Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics. However, owing to several life-threatening side effects and required enrollment in a registry with routine blood monitoring, clozapine is greatly underutilized in the US. Developing a medication as efficacious as clozapine with limited side effects would likely become the first-line therapy for schizophrenia and related disorders. In this review, we discuss the history of clozapine, landmark studies, and its clinical advantages and disadvantages. We further discuss the hypotheses for clozapine’s superior efficacy based on neuroreceptor binding, and the limitations of a receptor-based approach to antipsychotic development. We highlight some of the advances from pharmacogenetic studies on clozapine and then focus on studies of clozapine using unbiased approaches such as pharmacogenomics and gene expression profiling. Finally, we examine how these approaches could provide insights into clozapine’s mechanism of action and side-effect profile, and lead to novel and improved therapeutics.

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Chronic Paroxetine Treatment Prevents the Emergence of Abnormal Electroencephalogram Oscillations in Huntington’s Disease Mice

Abstract

Disturbance of rapid eye movement (REM) sleep appears early in both patients with Huntington’s disease (HD) and mouse models of HD. Selective serotonin reuptake inhibitors are widely prescribed for patients with HD, and are also known to suppress REM sleep in healthy subjects. To test whether selective serotonin reuptake inhibitors can correct abnormal REM sleep and sleep-dependent brain oscillations in HD mice, we treated wild-type and symptomatic R6/2 mice acutely with vehicle and paroxetine (5, 10, and 20 mg/kg). In addition, we treated a group of R6/2 mice chronically with vehicle or paroxetine (20 mg/kg/day) for 8 weeks, with treatment starting before the onset of overt motor symptoms. During and after treatment, we recorded electroencephalogram/electromyographm from the mice. We found that both acute and chronic paroxetine treatment normalized REM sleep in R6/2 mice. However, only chronic paroxetine treatment prevented the emergence of abnormal low-gamma (25–45 Hz) electroencephalogram oscillations in R6/2 mice, an effect that persisted for at least 2 weeks after treatment stopped. Chronic paroxetine treatment also normalized REM sleep theta rhythm in R6/2 mice, but, interestingly, this effect was restricted to the treatment period. By contrast, acute paroxetine treatment slowed REM sleep theta rhythm in WT mice but had no effect on abnormal theta or low-gamma oscillations in R6/2 mice. Our data show that paroxetine treatment, when initiated before the onset of symptoms, corrects both REM sleep disturbances and abnormal brain oscillations, suggesting a possible mechanistic link between early disruption of REM sleep and the subsequent abnormal brain activity in HD mice.

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Moving Beyond Serendipity to Mechanism-Driven Psychiatric Therapeutics

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Evidence-Based Psychotherapy: Advantages and Challenges

Abstract

Evidence-based psychotherapies have been shown to be efficacious and cost-effective for a wide range of psychiatric conditions. Psychiatric disorders are prevalent worldwide and associated with high rates of disease burden, as well as elevated rates of co-occurrence with medical disorders, which has led to an increased focus on the need for evidence-based psychotherapies. This chapter focuses on the current state of evidence-based psychotherapy. The strengths and challenges of evidence-based psychotherapy are discussed, as well as misperceptions regarding the approach that may discourage and limit its use. In addition, we review various factors associated with the optimal implementation and application of evidence-based psychotherapies. Lastly, suggestions are provided on ways to advance the evidence-based psychotherapy movement to become truly integrated into practice.

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3 products to improve firefighter, EMS provider safety

At the Fire-Rescue Med 2017 Conference, I saw three EMS products that really caught my attention. Enough so that I took the time to speak at length with each of the vendor representatives. When I look at new fire and EMS equipment, I have three evaluation criteria: 1. Will it make the job safer for the firefighter or medic" 2. Will it make the firefighter or medic more effective" 3. Will it make the ...

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Quantitative Pneumatic Otoscopy Using a Light-Based Ranging Technique

Abstract

Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child’s most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.

We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.

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Application of the Rat Grimace Scale as a Marker of Supraspinal Pain Sensation after Cervical Spinal Cord Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Histamine H 4 receptor signalling in tongue cancer and its potential role in oral carcinogenesis - a short report

Abstract

Purpose

Recent reports indicate that histamine and its novel, high-affinity histamine H₄ receptor (H₄R) play a role in carcinogenesis, and thus H₄R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H₄R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess H₄R expression in OTSCC patients and in OTSCC-derived cell lines.

Methods

Biopsies taken from OED, OTSCC and healthy oral mucosa were studied by immunostaining. Primary human oral keratinocytes (HOKs) and two OTSCC-derived cell lines (HSC-3 and SCC-25) were used for the in vitro studies. Quantitative real-time PCR was used to measure oncogene expression in the stimulated HOKs.

Results

We found that H₄R-immunoreactivity was significantly reduced in the OED and OTSCC samples, especially in the samples with higher histopathological grades and noticeably increased mast cell counts. The presence of H₄R in HSC-3 cells had clearly waned, in contrast to the HOKs. Gene expression data indicated that histamine-relevant inflammatory and environmental elements may participate in the regulation of oncogenes.

Conclusions

Our results suggest an association between H₄R and oral carcinogenesis. Furthermore, our findings raise a potential implication of histamine-mediated factors in the regulation of oncogenes, possibly via mast cells, as crucial components of the tumor microenvironment. The identification of new elements that govern oral cancer development is highly relevant for the development of novel therapeutic approaches in OTSCC.

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Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report

Abstract

Purpose

Pre-operative progesterone treatment of breast cancer has been shown to confer survival benefits to patients independent of their progesterone receptor (PR) status. The underlying mechanism and the question whether such an effect can also be observed in PR negative breast cancer cells remain to be resolved.

Methods

We performed proteome profiling of PR-positive and PR-negative breast cancer cells in response to progesterone using a phospho-kinase array platform. Western blotting was used to validate the results. Cell-based phenotypic assays were conducted using PR-positive and PR-negative breast cancer cells to assess the effect of progesterone.

Results

We found that progesterone induces de-phosphorylation of 12 out of 43 kinases tested, which are mostly involved in cellular invasion and migration regulation. Consistent with this observation, we found through cell-based phenotypic assays that progesterone inhibits the invasion and migration of breast cancer cells independent of their PR status.

Conclusion

Our results indicate that progesterone can inhibit breast cancer cell invasion and migration mediated by the de-phosphorylation of kinases. This inhibition appears to be independent of the PR status of the breast cancer cells. In a broader context, our study may provide a basis for an association between progesterone treatment and recurrence reduction in breast cancer patients, thereby providing a lead for modelling a randomized in vitro study.

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Evaluation of human cytomegalovirus antigen expression in invasive breast carcinoma in a population of Iranian patients

Abstract

Background

The role of human cytomegalovirus (HCMV) in the development of breast carcinoma is questionable. The aim of this study was to evaluate the expression of the immediate early antigen (IE) of HCMV in breast carcinoma and its association with some clinicopathologic factors in a population of Iranian patients.

Methods

Formalin-fixed and paraffin-embedded tissue blocks from the pathology laboratories of the Azahra and Shahid Beheshti hospitals, Isfahan, Iran, from 2013 to 2016, were used in the study. We used immunohistochemistry and real-time PCR to detect the IE-antigen of HCMV in breast carcinoma, normal tissue adjacent to carcinoma, and normal tissue from mammoplasty specimens.

Results

A total of 96 samples were evaluated: 70 invasive breast carcinoma of different histologic subtypes and 26 mammoplasty normal breast tissues. All the samples were negative for IE-antigen expression. No relationship was seen between breast cancer and HCMV in this study.

Conclusions

The results of this study failed to show any relationship between HCMV and the development of breast carcinoma.

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Synchronous bilateral tonsil carcinoma: case presentation and review of the literature

Abstract

Background

The incidence of synchronous bilateral tonsil carcinoma seems to be underreported. For adequate oncologic treatment, it is mandatory to remove all primaries to prevent recurrence or metachronic disease. The purpose of this manuscript is to provide a comprehensive review on this topic and to emphasize the need of bilateral tonsillectomy in cases of cancer of unknown primary (CUP) as well as in the case of a unilateral tonsillar carcinoma.

Material and methods

A systematic review of the literature was performed for “bilateral tonsillar neoplasm”, “synchronous cancer of the oropharynx” and “cancer of unknown primary in head and neck”.

Results

We present a clinical case with bilateral tonsillar carcinoma in initially suggested cancer of unknown primary. Clinically, both tonsillar sites were unsuspicious, but in PET/CT an ipsilateral enhancement of the tonsil area was detected. The pathological work up of bilateral tonsillectomy specimens revealed bilateral squamous cell carcinoma with HPV-type 16 positivity. The review of the literature revealed 29 cases of bilateral tonsil cancer.

Conclusion

The handling of tonsillar tissue in the frame of panendoscopy in the case of CUP is still controversial. We recommend a bilateral tonsillectomy as a routine procedure for cancer of unknown primary as well as unilateral tonsillar carcinoma. Herewith the detrimental consequences of occult metachronous contralateral tonsillar carcinoma can be prevented.

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Quantitative Pneumatic Otoscopy Using a Light-Based Ranging Technique

Abstract

Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child’s most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.

We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.

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Safer VL intubation: Don't insert the ET tube too deep

Another great intubation tip from Williamson County EMS.

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Primary epithelial salivary gland tumours in children and adolescents

Primary epithelial tumours of the salivary glands are very rare in paediatric patients. The aim of this study was to evaluate the clinical course, treatment, and outcomes of these uncommon neoplasms based on the authors’ experience and the recent literature. The medical charts of 12 female patients and seven male patients with primary epithelial salivary gland tumours were reviewed. All were under 19 years of age and underwent surgical treatment between 1994 and 2016. The results of this group of paediatric patients were compared with those of 621 adult patients.

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Immediate full-arch rehabilitation of the severely atrophic maxilla supported by zygomatic implants: a prospective clinical study with minimum follow-up of 6 years

The aim of this study was to evaluate the outcomes of immediate full-arch prostheses supported by zygomatic implants alone or in combination with standard fixtures after a minimum of 6 years of loading. From October 2008 to April 2010, 15 patients with severely atrophic maxillae were treated using four zygomatic implants or two zygomatic implants in conjunction with two conventional fixtures. All subjects received a fixed screw-retained prosthesis within 3hours of surgery, while the final restoration was delivered after 6 months.

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Retraction Note: Human cathelicidin LL-37 enhance the antibiofilm effect of EGCG on Streptococcus mutans

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Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate

Viral Immunology , Vol. 0, No. 0.


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Helper T Cell Responses to Respiratory Viruses in the Lung: Development, Virus Suppression, and Pathogenesis

Viral Immunology , Vol. 0, No. 0.


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Is There Detectable Long-term Depletion of Genetic Variation in Freshwater Fish Species Affected by an Oil Spill?

Abstract

Oil spills might lead to severe environmental impacts to the affected fauna, disrupting local food webs, and causing mass mortality in many species. However, little is known about long-term impacts of oil spills, or even if such impacts can be detectable after several generations. In this study, we investigate the genetic variability of three freshwater species—Mimagoniates microlepis (Characiformes: Characidae), Scleromystax barbatus (Siluriformes: Callichthyidae), and Phalloceros harpagos (Cyprinodontiformes: Poeciliidae)—in rivers that were affected by a large oil spill in the state of Paraná, southern Brazil, on February of 2001. Samples were obtained from nine different locations, such that rivers that were directly affected by the oil spill could be compared with similar rivers in the same region that were unaffected. A fragment of the cytochrome C oxidase subunit I mitochondrial gene was sequenced from each specimen, and the level of genetic variability was assessed. Based on estimates of haplotype and nucleotide diversity, no impact of the oil spill could be detected in impacted rivers. These results suggest that fish populations in the region showed resilience to the pollutant, such that immigration from other locations was able to reestablish levels of genetic variability comparable to those of unimpacted rivers.

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Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation

Abstract

Background

Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis.

Methods

In this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated.

Results

We show that E2A-PBX1⁺ leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process.

Conclusion

These data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype.

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Quality of compounded hydrocortisone capsules used in the treatment of children

Objectives

Due to the lack of paediatric-licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this ‘real world’ evaluation of pharmacy-compounded paediatric hydrocortisone capsules.

Methods

Capsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method was performed based on the European Pharmacopeia.

Results

In a total of 61 batches that were sent, 5 batches could not be analysed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. Fifty-six batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug.

Conclusions

Compounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities.

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