Viruses, Vol. 9, Pages 279: Venezuelan Equine Encephalitis Virus Capsid—The Clever Caper

Viruses, Vol. 9, Pages 279: Venezuelan Equine Encephalitis Virus Capsid—The Clever Caper

Viruses doi: 10.3390/v9100279

Authors: Lindsay Lundberg Brian Carey Kylene Kehn-Hall

Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus that is vectored by mosquitos and cycled in rodents. It can cause disease in equines and humans characterized by a febrile illness that may progress into encephalitis. Like the capsid protein of other viruses, VEEV capsid is an abundant structural protein that binds to the viral RNA and interacts with the membrane-bound glycoproteins. It also has protease activity, allowing cleavage of itself from the growing structural polypeptide during translation. However, VEEV capsid protein has additional nonstructural roles within the host cell functioning as the primary virulence factor for VEEV. VEEV capsid inhibits host transcription and blocks nuclear import in mammalian cells, at least partially due to its complexing with the host CRM1 and importin α/β1 nuclear transport proteins. VEEV capsid also shuttles between the nucleus and cytoplasm and is susceptible to inhibitors of nuclear trafficking, making it a promising antiviral target. Herein, the role of VEEV capsid in viral replication and pathogenesis will be discussed including a comparison to proteins of other alphaviruses.

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Stability of intraoral vertical ramus osteotomies for mandibular setback: a longitudinal study

This study aimed to investigate the postoperative longitudinal skeletal changes and stability following intraoral vertical ramus osteotomies (IVRO) for orthognathic mandibular setback, and the possible risk factors that might affect the stability. A retrospective cohort study was conducted. Lateral cephalograms were analyzed for the predictor (magnitude of setback and adjunctive procedures) and outcome (stability of vertical and horizontal dimensions) variables at six time points. A total of 152 patients (mean age 24.2 years) were included in the study. (Source: International Journal of Oral and Maxillofacial Surgery)

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Iodine-125 brachytherapy alone for advanced primary parotid gland carcinoma

This study aimed to evaluate the efficacy of iodine-125 (125I) brachytherapy alone for the treatment of advanced parotid gland carcinoma and to identify predictors of tumour control and patient survival. Primary parotid gland carcinoma patients (n=23) treated with 125I brachytherapy alone between 1 October 2005 and 31 July 2013 at Peking University Stomatology Hospital were enrolled in this retrospective study. All had clinical stage IV disease. The prescribed dose was 60 –160Gy. The local control rate, survival rate, and predictors of the prognosis were evaluated. (Source: International Journal of Oral and Maxillofacial Surgery)

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Orthodontic camouflage versus orthodontic-orthognathic surgical treatment in class II malocclusion: a systematic review and meta-analysis

This systematic review was performed to compare dental, skeletal, and aesthetic outcomes between orthodontic camouflage and surgical-orthodontic treatment, in patients with a skeletal class II malocclusion and a retrognathic mandible who have already finished their growth period. A literature search was conducted, and a modified Downs and Black checklist was used to assess methodological quality. The meta-analysis was conducted using the DerSimonian –Laird random-effects method to obtain summary estimates of the standardized mean differences and corresponding 95% confidence intervals. (Source: International Journal of Oral and Maxillofacial Surgery)

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Dentist Puts Himself in 'Star Wars' for Wonderfully Cheesy Ad

An Arkansas dentist named Dr. Abernathy used some special editing to put himself in the Death Star trench run from 1977's Star Wars: A New Hope . And like Luke Skywalker, he didn't need his instruments to get the job done.

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Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract

Background

. Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia.

Methods

. Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h⁻¹ for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively.

Results

. A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min (P=0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine (P=0.009). At three months, no differences between groups were noted.

Conclusions

. Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up.

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Diastolic dysfunction and sepsis: the devil is in the detail

Diastolic dysfunction is the consequence of impaired left ventricular relaxation, decreased recoil and decreased ventricular compliance.¹ Before the era of tissue Doppler imaging (TDI), pulmonary vein Doppler imaging in conjunction with transmitral Doppler, was a major tool in identifying diastolic dysfunction, also in septic shock patients.² Pulmonary vein Doppler assessment with a systolic (S) < diastolic (D) flow velocity supports the finding of elevated left ventricular filling pressures in a euvolaemic patient.

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Age and inflammation after cardiac surgery

The cardiac surgical population is aging and these patients have increased expectations with respect to quantity and quality of postoperative survival. Some of the physiological changes related to aging that impact surgical outcomes are better understood than others, and recently we are also beginning to gain a better understanding of the impact of aging on immunity and the immune response to surgery.¹²

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An algorithm for suboptimally placed supraglottic airway devices: the choice of videolaryngoscope

Editor—We agree with Zundert and colleagues¹ that anaesthetists sometimes accept lower standards for supraglottic airway device (SAD) placement than for tracheal tube placement. They advocate the use of videolaryngoscopy to correct a suboptimal SAD position using an algorithm, however they do not make any specific recommendation about which type of videolaryngoscope to use. A variety of classifications of videolaryngoscopes exist,^2–5 and some classes (for example, channelled videolaryngoscopes) might prove to be very difficult to use in this situation; some may even cause trauma in the reduced space available when an SAD is present. Zundert and colleagues ⁶ have previously referenced the C-MAC videolaryngoscope (Karl Storz, Tuttlingen, Germany) in this situation, but presumably other Macintosh-type bladed scopes would be acceptable. We would be keen to learn whether they have experience of other videolaryngoscopes, and we also wondered whether they had considered the place of the optical stylet.

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Fading whispers down the lane: signal propagation in anaesthetized cortical networks

An active area of enquiry in the neuroscientific investigation of general anaesthesia is the question of whether anaesthetic-induced unconsciousness is mediated by bottom-up or top-down mechanisms in the brain. Candidates for the bottom-up approach include suppression of arousal centres in the brainstem and diencephalon,¹² activation of sleep-promoting neurones or nuclei in similar locations,¹³ blockade of sensory information en route from the thalamus to the cortex,⁴ and a disabled thalamic conductor for the neuronal orchestra of the cortex.⁵ Candidates for the top-down approach include direct effects on long-latency activity in cortical networks,⁶ with a consequent disruption of higher-order information synthesis that occurs beyond the level of the primary sensory cortex.^7–9 This bottom-up vs top-down distinction is almost surely artificial given the integrated circuits required for the normal function of neural systems and the widespread effects of general anaesthetics on the brain. We recently proposed that anaesthetics alter the level of consciousness (e.g. awake vs somnolent) through bottom-up mechanisms while degrading the contents of consciousness (e.g. the particular qualities of experience) through top-down mechanisms.¹⁰ Developing a clearer understanding of these processes is important because it can inform (i) the neurobiology of consciousness, a fundamental question in science, and (ii) our approach to brain monitoring, a fundamental and unmet challenge in clinical anaesthesia. However, it is difficult to address this question by investigating individual brain areas or molecular targets in the laboratory and also difficult to distinguish cortical and subcortical mechanisms through human neuroimaging and neurophysiology. In this issue of the British Journal of Anaesthesia, Hentschke and colleagues¹¹ examine an intermediate level of neuroanatomy and neurophysiology in a cortical slice model, finding more profound effects of isoflurane on signal propagation through the cortex than to the cortex.

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Speaking up: does anaesthetist gender influence teamwork and collaboration?

Speaking up can be defined as explicitly communicating observations or concerns, requesting clarification or explanation, or explicitly challenging a colleague's decision or action.¹ Speaking up provides an opportunity to intervene before patient harm occurs, or to mitigate actual harm, and is a key element in effective teamwork and collaboration.² The importance of speaking up is most evident in its absence, where colleagues remain silent or make ineffectual attempts at speaking up, and erroneous actions proceed to cause patient harm. There are many prominent examples where failing to speak up in an effective manner has contributed to accidents and catastrophes in aviation,³ space exploration⁴ and in healthcare.⁵

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Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis

Abstract

Background

To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain.

Methods

We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2–4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain.

Results

Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate.

Conclusions

Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.

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Special section on pain: progress in pain assessment and management

This issue of the British Journal of Anaesthesia has a special section on pain, featuring a number of editorials, reviews and original articles across a range of areas in pain medicine. The last BJA special issue on pain medicine was in July 2013, entitled "Managing pain: recent advances and new challenges", as summarized in the lead editorial of that issue.¹ A similar title could be used for this month's special section. Pain medicine continues to evolve, with advances in acute, chronic and cancer pain understanding and management. However, the challenges remain, and arguably, increase, as our population ages: Pain is one of the biggest causes of disability globally, with musculoskeletal pain being the leading cause of disability in most countries in 2015.²³ Managing pain successfully - acute, chronic or cancer - is an area where there is potential major clinical benefit both at an individual and societal level.

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The potential clinical benefits of medicines optimisation through comprehensive geriatric assessment, carried out by secondary care geriatricians, in a general practice care setting in North Staffordshire, UK: a feasibility study

Objectives

To evaluate the feasibility and potential clinical benefits of medicines optimisation through comprehensive geriatric assessment (CGA) of frail patients with multiple conditions, by secondary care geriatricians in a general practice care setting.

Methods

Seven general practitioner (GP) practices in one region of Stoke-on-Trent volunteered to take part. GPs selected patients (n=186) who were local permanent residents, at least 65 years old and on eight or more medications per day. Patients were sent a written invitation outlining the assessment purpose/format. Prior to patient assessments, primary care staff prepared packs detailing patient medical history, recent consultations, current medications, recent laboratory tests and social circumstances. One hour was allocated for the CGA per patient, with one of three geriatricians, to enable sufficient time to explore all relevant aspects. Assessment comprised a full history, thorough clinical examination, assessment of balance and mobility, mental function and information on home environment and support arrangements. After consultation, geriatricians made recommendations regarding further assessments, investigations or medication changes. Geriatricians entered their main findings and recommendations onto a standard template.

Results

In total, 687 recommendations for changes in patients' medication regimens were made for 169 (91%) patients. In 17 (9%) patients there was no recommendation to alter medications. This resulted in an average of four alterations in medication per patient. The predominant changes to medications were to stop medications (34%) or to reduce the dosage (24%). Starting a new medication represented 18% of all the medication changes. Adherence rates to geriatrician medication recommendations were 72% at 6 months and 65% at 12 months.

Conclusions

CGA of older patients with complex needs, by geriatricians in a general practice care setting, is feasible. Our study demonstrated constructive collaboration between GPs and geriatricians from secondary care, suggesting further studies and clinical trials are feasible and have scope to yield beneficial outcomes.

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A national survey exploring oral healthcare service provision across Australian community pharmacies

Objectives

This study investigated pharmacists' and pharmacy assistants' current practices and perspectives with regard to oral healthcare provision across Australian community pharmacies.

Design

Cross-sectional study. A questionnaire for each pharmacist and pharmacy assistant cohort was developed and administered by online or postal means. Pearson's ² test was used to examine relationships between categorical variables.

Participants

Pharmacists and pharmacy assistants working within 2100 randomly selected Australian community pharmacies.

Results

The overall response rate was 58.5% (644/1100) for the pharmacist cohort and 28% (280/1000) for the pharmacy assistant cohort. This represents pharmacy staff responses from 803 community pharmacies across Australia (approximately 14.6%, 803/5500 of community pharmacies nationally). Overall, the majority of pharmacists (80.2%; 516/644) and pharmacy assistants (83.6%; 234/280) reported providing oral health advice/consultations to health consumers up to five times each week. More than half of community pharmacists and pharmacy assistants were involved in identifying signs and symptoms for oral health problems; and the majority believed health consumers were receptive to receiving oral health advice. Additionally, more than 80% of pharmacists and 60% of pharmacy assistants viewed extended oral healthcare roles positively and supported integrating them within their workplace; extended roles include provision of prevention, early intervention and referral to oral healthcare services. The most commonly reported barriers to enhance pharmacy staff involvement in oral healthcare within Australian community pharmacies include lack of knowledge, ongoing training and resources to assist practice.

Conclusion

This study highlights that Australian pharmacists have an important role in oral health and provides evidence supporting the need for growing partnerships/collaborations between pharmacy and dental healthcare professionals and organisations to develop, implement and evaluate evidence-based resources, interventions and services to deliver improved and responsive oral healthcare within Australian communities.

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Non-adherence to immunosuppressants following renal transplantation: a protocol for a systematic review

Introduction

Adherence to immunosuppressant medication is essential for renal transplant recipients. This review aims to summarise what is known about non-adherence, with a view to providing comprehensive evidence to inform strategies aimed at advancing adherent behaviour.

Methods and analysis

A systematic review of quantitative studies that report adherence to immunosuppressants in adult (over 18 years) renal transplant recipients. The review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines; study quality will be assessed using the Downs and Black checklist. Systematic searches will be completed across relevant databases. Two reviewers will independently extract data using a predefined data extraction form. We will summarise the operationalisation of adherence across studies and use narrative synthesis to identify factors associated with non-adherence. A meta-analysis will be conducted if there is sufficient homogeneity, and available data, across studies to estimate the prevalence of non-adherence in renal transplant recipients. Heterogeneity will be assessed using the I² test. Survival analysis will be conducted to estimate hazard ratios to explore the impact of non-adherence on graft survival, graft failure and patient survival.

Ethics and dissemination

Findings will be published in a peer-reviewed journal and disseminated at conferences for professionals and researchers. Review outcomes will help support clinical practice by highlighting the extent of non-adherence among adults, and in doing so, signpost the need for suitable intervention.

Trial registration number

PROSPERO registration number (CRD42016038751).

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Efficacy and safety of instantaneous wave-free ratio in patients undergoing coronary revascularisation: protocol for a systematic review

Introduction

Effective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous 'wave-free' ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted.

Methods and analysis

This is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Ethics and dissemination

Ethics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication.

Trial registration number

This protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.

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Cross-sector user and provider perceptions on experiences of shared-care clozapine: a qualitative study

Objectives

(1) To explore individual perceptions on experiences of people receiving and/or delivering a shared-care clozapine serviceand (2) to gain an understanding of effectiveness and acceptability of shared-care clozapine.

Design

Interpretative phenomenological analysis guided the delivery and analysis of a semistructured interview and focus group study designed to explore participant experience of shared-care clozapine. Ethical approval 13/EM/0286 was gained in July 2013 from East Midlands—Nottingham 1 REC.

Participants

Eight stakeholder groups from Adult and Forensic Mental Health involved in shared-care clozapine provision delivered in primary care were identified for recruitment from one mental health trust in England (six different groups of healthcare professionals (HCPs), clozapine service users (CSUs) and their carers). To be eligible for recruitment, all potential participants had to be either providing, receiving or the carer of a person receiving clozapine by shared care.

Results

32 HCPs and 6 CSUs were recruited and 14 interviews and 6 participant homogenous focus groups were run. Four shared superordinate themes were identified: Clozapine Process, The Sharing of Care, The Provision of Care and Multi-professional Relationships. Differences between Adult and Forensic engagement in shared care were noted and both HCP and CSU relationships were mapped to the Wish conceptual framework of relationships to provide insight into how shared-care clozapine can provide a mechanism for provision of person-centred care, which was present in the Forensic HCP–CSU but not General Adult HCP–CSU relationship.

Conclusions

The Forensic HCP/CSU relationship demonstrated how cross-sector working through shared-care clozapine can provide a mechanism for provision of person-centred care by enabling a person-centred focus to care delivery which supported CSUs to live as independently as possible. Person-centred care demonstrably improves patient care outcomes and wider implementation of shared-care clozapine could provide greater integration of people with serious mental illness and reduce stigma within the community while improving patient outcomes.

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Canada-DONATE study protocol: a prospective national observational study of the medical management of deceased organ donors

Introduction

Research on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials.

Methods and analysis

This ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex.

Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data.

Ethics and dissemination

This study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals.

Trial registration number

NCT03114436.

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Clinical and pathological analyses of tuberculosis in the oral cavity: report of 11 cases

Publication date: Available online 28 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Wu-tong Ju, Yong Fu, Ying Liu, Yi-ran Tan, Min-jun Dong, Li-zhen Wang, Jiang Li, Lai-ping Zhong
ObjectiveTo analyze tuberculosis (TB) in the oral cavity according to clinical appearance, clinical differential diagnosis, treatment, and outcome.Study DesignWe enrolled 11 patients with TB in the oral cavity between November 2012 and November 2016. Glossal lymphoid TB was excluded. Clinical symptoms, auxiliary examinations, treatments, and outcomes were recorded and analyzed.ResultsThere were six men and five women, with a mean age of 59 years. Five patients presented with ulcer, five with a mass, and one with osteomyelitis. Excisional biopsy was performed in three patients, mass resection in seven, and curettage of mandibular lesion in one. After pathological diagnosis of TB in the oral cavity in eight patients, six of them underwent purified protein derivative examination; four of them were positive and received drug therapy. The mean follow-up period was 24.9 months, with no recurrence.ConclusionsTB in the oral cavity is rare, with no specific clinical appearance. Pathology, acid-fast staining, PCR, or DNA test for Mycobacterium tuberculosis is useful for final diagnosis. Surgery is suggested as the treatment of choice, with good clinical outcomes.



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Relationships matter in oral cancer: will single stain immunohistochemistry become irrelevant in the age of multispectral imaging?

Publication date: Available online 28 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): R. Bryan Bell, Bernard A. Fox




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Top Reviewers 2016

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Auditory Evoked Potential Mismatch Negativity in Normal-Hearing Adults

Abstract Introduction Mismatch Negativity (MMN) corresponds to a response of the central auditory nervous system. Objective The objective of this study is to analyze MMN latencies and amplitudes in normal-hearing adults and compare the results between ears, gender and hand dominance. Methods This is a cross-sectional study. Forty subjects participated, 20 women and 20 men, aged 18 to 29 years and having normal auditory thresholds. A frequency of 1000Hz (standard stimuli) and 2000Hz (deviant stimuli) was used to evoked the MMN. Results Mean latencies in the right ear were 169.4ms and 175.3ms in the left ear, with mean amplitudes of 4.6μV in the right ear and 4.2μV in the left ear. There was no statistically significant difference between ears. The comparison of latencies between genders showed a statistically significant difference for the right ear, being higher in the men than in women. There was no significant statistical difference between ears for both right-handed and left-handed group. However, the results indicated that the latency of the right ear was significantly higher for the left handers than the right handers. We also found a significant result for the latency of the left ear, which was higher for the right handers. Conclusion It was possible to obtain references of values for the MMN. There are no differences in the MMN latencies and amplitudes between the ears. Regarding gender, the male group presented higher latencies in relation to the female group in the right ear. Some results indicate that there is a significant statistical difference of the MMN between right- and left-handed individuals.

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The Temporalis Muscle Flap for Palate Reconstruction: Case Series and Review of the Literature

Abstract Introduction The temporalis myofascial (TM) is an important reconstructive flap in palate reconstruction. Past studies have shown the temporalismyofascial flap to be safe as well as effective. Free flap reconstruction of palate defects is also a popular method used by contemporary surgeons. We aim to reaffirm the temporalis myofascial flap as a viable alternative to free flaps for palate reconstruction. Objective We report our results using the temporalis flap for palate reconstruction in one of the largest case series reported. Our literature review is the first to describe complication rates of palate reconstruction using the TM flap. Methods Retrospective chart review and review of the literature. Results Fifteen patients underwent palate reconstruction with the TMflap. There were no cases of facial nerve injury. Five (33%) of these patients underwent secondary cranioplasty to address temporal hollowing after the TM flap. Three out of fifteen (20%) had flap related complications. Fourteen (93%) of the palate defects were successfully reconstructed, with the remaining case pending a secondary procedure to close the defect. Ultimately, all of the flaps (100%) survived. Conclusion The TM flap is a viable method of palate defect closure with a high defect closure rate and flap survival rate. TM flaps are versatile in repairing palate defects of all sizes, in all regions of the palate. Cosmetic deformity created from TM flap harvest may be addressed using cranioplasty implant placement, either primarily or during a second stage procedure.

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Relationship of Tumor Thickness with Neck Node Metastasis in Buccal Squamous Cell Carcinoma: An Experience at a Tertiary Care Hospital

Abstract Introduction Squamous cell carcinoma is the most common malignancy of the head and neck, with the buccal mucosa being the most common site involved. Early locoregional metastasis is a hallmark of this disease, and early stage tumors may harbor metastatic nodes that are occult. Certain parameters can help identify high-risk patients for whom the pattern of occult nodal metastasis can be predicted. Tumor thickness is one such objective parameter. Objective To determine the relationship of tumor thickness with neck node metastasis in squamous cell carcinoma of the buccal mucosa. Methods A retrospective chart review of 102 patients with biopsy-proven squamous cell carcinoma of the buccal mucosa with N0 Necks was performed. All patients underwent tumor resection with neck dissection, and the tumor thickness was measured. Univariate and multivariate analyses were performed. Results A total of 102 patients, of which 73.53% were males and 26.47% were females. Themean age of the patients was 49.3 ± 11.1 years. It was found that the risk of neck node metastasis in buccal squamous cell carcinoma increases 35.5 times for a tumor thickness ≥ 2 mm, and the risk of neck nodemetastasis in buccal squamous cell carcinoma decreases by 0.58 times for each centimeter decrease in tumor size, while the rate of occult neck lymph node metastasis was found to be 37%. Conclusion We conclude that tumor thickness is significantly related with neck nodal metastasis in buccal squamous cell carcinoma, considering the age of the patient and the size of the tumor.

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Late-term Effects of Surgery on Nasal Functions in Patients who Underwent Total Laryngectomy Surgery

Abstract Introduction There is a common opinion that losing airway functions in total laryngectomy patients cause changes in nasal physiological rates. Studies conducted to review the subject present gaps, especially in terms of objective measurements. Objective We evaluated late-term effects of surgery on nasal functions in patients who underwent total laryngectomy surgery more than two years ago. Methods We included in the study 22 patients who had undergone total laryngectomy, as well as 24 healthy subjects with similar demographic characteristics as the control group. We performed acoustic rhinometry for intranasal volume and cross-sectional area measurements, saccharin test formeasurement of nasalmucociliary clearance, and smell identification test for evaluation of olfactory function in the patient and control groups. We compared and statistically analyzed the data obtained from the groups. Results In our study, although late-term (>2 years) measurements were not statistically significant, we detected more nasal passage patency in the patient group than in the control group. In smell identification test, lower scores were obtained in the patient group. The difference between measurements in both groups was statistically significant. Conclusion We believe that since the upper respiratory tract is disabled due to tracheostomy in patients with total laryngectomy, atrophy occurs in the late term and, consequently, nasal mucociliary clearance is impaired. We also see diminished olfactory function in total laryngectomy patients.

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Impact of Successful Choanal Atresia Repair on the Nasal Mucosa: A Preliminary Study

Abstract Introduction Themain histological features of the nasalmucosa in choanal atresia are distorted cilia, marked increase of mucous submucosal glands associated with marked reduction of goblet cell density, and lymphocytic cellular infiltration. Objective To study the nasal mucosal changes in cases of choanal atresia after successful repair compared with pre-repair mucosal histological features. Methods Tissue samples were taken from the inferior turbinate of 3 patients (1 bilateral and 2 unilateral) who were successfully operated. Then, the biopsies were subjected to histopathological, histochemical and immunohistochemical studies. After that, the results were compared with pre-repair findings in the choanal atresia side and in the normal side. Results Four biopsies (4 repaired choanal atresia sides) of the mucosa of the inferior turbinate revealed that 1 patient (who had a bilateral choanal atresia repaired), after achieving a patent choana for 8 months, had not completely recovered a normal nasal mucosa. The other 2 patients, after 18 and 23 months of achieving a patent choana, showed normal nasal cavities. Conclusion The main histological features of the nasal mucosa in choanal atresia could be reversed by surgery, making the patients regain their choanal patency, with their mucosae changing back to normal gradually with time.

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A Comparative Study between Universal Eclectic Septoplasty Technique and Cottle

Abstract Introduction Since the last century surgical correction of nasal septum deviation has been improved. The Universal Eclectic Technique was recently reported and there are still few studies dedicated to address this surgical approach. Objective The objective of this study is to compare the results of septal deviation correction achieved using the Universal Eclectic Technique (UET) with those obtained through Cottle's Technique. Methods This is a prospective study with two consecutive case series totaling 90 patients (40 women and 50 men), aged between 18 and 55 years. We divided patients into two groups according to the surgical approach. Fifty-three patients underwent septoplasty through Universal Eclectic Technique (UET) and thirty-seven patients were submitted to classical Cottle's septoplasty technique. All patients have answered the Nasal Obstruction Symptom Evaluation Scale (NOSE) questionnaire to assess pre and postoperative nasal obstruction. Results Statistical analysis showed a significantly shorter operating time for the UET group. Nasal edema assessment performed seven days after the surgery showed a prevalence of mild edema in UET group and moderate edema in Cottle's technique group. In regard to complication rates, UET presented a single case of septal hematoma while in Cottle's technique group we observed: 02 cases of severe edemas, 01 case of incapacitating headache, and 01 complaint of nasal pain. Conclusion The Universal Eclectic Technique (UET) has proven to be a safe and effective surgical technique with faster symptomatic improvement, low complication rates, and reduced surgical time when compared with classical Cottle's technique.

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False acute kidney injury alert due to model car fuel ingestion

We report a case of accidental ingestion of model car fuel (Optifuel) resulting in an apparent elevation of serum creatinine of 274 µmol/L (3.1 mg/dL) as measured by the Jaffe (alkaline picrate) reaction, which resulted in an acute kidney injury (AKI) stage 3 alert being reported. Optifuel contains nitromethane, which has been reported to interfere in the Jaffe reaction causing falsely high creatinine measurements. The laboratory staff were vigilant about this potential interfering substance so repeated the analysis of the creatinine using an enzymatic method that showed a markedly lower result of 47 µmol/L (0.5 mg/dL). This report highlights the ability of nitromethane to potentially mimic AKI and the importance of being aware of the limitations of biochemical tests to avoid misinterpretation of results and instigating inappropriate treatment.

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Typical carcinoid involving the main carina managed with arterial embolisation, endobronchial resection and ablation, ultimately followed by carinal resection

Bronchial carcinoids are uncommon pulmonary tumours, and the gold standard management is surgical resection. Their management is often complicated by their proximal location and propensity to bleed when manipulated. A 22-year-old man was found to have typical carcinoid tumour involving the carina and surgical resection was considered not feasible. We report our experience with a multimodality approach involving arterial embolisation, with subsequent endobronchial resection and ablation. Residual disease was found and managed with definitive carinal resection.

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Possible congenital dilatation of the pancreatic duct

The main pancreatic duct can become dilated in a number of conditions. We describe a patient with gross dilatation of the main pancreatic duct without evidence of causative underlying pathology suggesting congenital dilatation of the pancreatic duct. A 36-year-old man presented with signs of intestinal obstruction and a history of surgery for congenital pyloric stenosis. Incidental findings on CT showed a massively dilated main pancreatic duct. On MRI there was no duct irregularity or solid mural nodule, making a main duct intraductal papillary mucinous neoplasm unlikely. Endoscopic ultrasound findings were in keeping with those on MRI. Fine needle aspiration revealed a non-viscous fluid with a low carcinoembryonic antigen and high amylase concentration, consistent with normal pancreatic fluid levels rather than a mucinous collection. After 1 year, the cyst remains unchanged. This patient will be kept under surveillance with yearly MRI.

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Retroperitoneal teratoma simulating giant adrenal myelolipoma: a diagnostic puzzle

Teratoma is a germ-cell tumour that is common in para-axial regions. Retroperitoneal teratoma is rare and comprise only about 1% of all teratomas. We present a 21-year-old female who presented with a lump in the abdomen. After radiological investigations, she was diagnosed as case of adrenal myelolipoma which on excision turned out histologically to be retroperitoneal teratoma. Our case highlights the limitation of radiological investigations in preoperative diagnosis of teratoma.

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Acromegaly with hypophosphataemia: McCune-Albright syndrome

A 38-year-old man presented with excessive height gain and progressive enlargement of the extremities since childhood. This was compounded by lower limb deformities over the past 5 years. On examination, his height was 196 cm, he had macroglossia, acral enlargement, seborrhoea, hyperhidrosis—suggesting acrogigantism. He had facial asymmetry, wind-swept deformity of lower limbs and a café-au-lait macule over his trunk. Investigations revealed normal-sized pituitary gland with dysplastic cranial bones. Isotope bone scintigraphy was suggestive of polyostotic fibrous dysplasia. A diagnosis of McCune-Albright syndrome was made and trans-sphenoidal hypophysectomy was undertaken. He had persistent hypophosphataemia. Tubular reabsorption of phosphate adjusted for glomerular filtration rate was low and serum FGF-23 level was high. Ga-DOTATATE scintigraphy showed somatostatin-receptor expression in all the dysplastic lesions. FGF-23 produced by the bony lesions could counteract the phosphate-retaining effect of GH excess resulting in hypophosphataemia, which further worsened following hypophysectomy.

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Simultaneous combined complete tear of radial and ulnar collateral ligaments of thumb in an adolescent

Isolated tear of collateral ligaments of thumb are common but combined injuries of both radial and ulnar collateral ligaments are rare. These cases are reported in athletes involved in high-impact sports. Here, we report a case of a 15-year-old boy with pain at base of the thumb and instability following low-impact sporting activity. On subsequent clinicoradiological assessment, simultaneous combined complete tear of both radial and ulnar collateral ligaments of the thumb was noted. Delayed primary repair of both collateral ligaments was done. This case highlights the rarity of this type of injury in an adolescent and also the use of appropriate clinical tests and imaging modalities for early diagnosis of such injuries. Restoration of joint stability as early as possible either by repair or reconstruction of ligaments needs to be considered to prevent secondary osteoarthritis of metacarpophalangeal joint.

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HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining

Approximately 1%–10% of patients with HIV infection have been reported to have salivary gland enlargement. Parotid swelling in patients with HIV is often associated with salivary gland disease, including benign lymphoepithelial cysts (BLECs). The presence of BLEC can serve as an indicator of HIV infection, and the diagnosis of HIV-associated BLEC is usually based on clinical course, HIV confirmatory blood testing, such as western blot or viral detection, and imaging studies, but not on biopsies or immunostaining. To exclude other diseases such as tuberculosis and malignant lymphoma and to further improve the diagnostic accuracy of BLEC, the detection of the HIV-1 p24 antigen by immunohistochemistry is a useful diagnostic method. We report a case of a 65-year-old Japanese man with swelling of the parotid glands and HIV-associated BLEC confirmed via HIV-1 p24 immunohistochemical staining.

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Fatal familial insomnia

Fatal familial insomnia: Abbreviated FFI. An hereditary prion disease characterized by disrupted sleep (insomnia), motor abnormalities (myoclonus, ataxia, dysarthria, dysphagia, and pyramidal signs), and hyperactivation of the autonomic nervous system. Due to a missense mutation at codon 178 of the prion protein gene on chromosome 20. A sporadic form of fatal insomnia is also known.

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Upcoming COCA Call: October 12, 2017: The Role of Healthcare Professionals in Protecting Older Adults against Influenza

Healthcare professionals (HCPs) play a critical role in protecting older adults (age 65 years and older) against influenza (flu). Despite concerted efforts to promote annual influenza vaccination in older adults, persistent knowledge gaps exist regarding the burden of disease and the risk of flu and related complications for this vulnerable population. According to recent research, the phenomenon known as immunosenescence leaves older adults less responsive to standard influenza vaccines. HCPs play a critical role in strongly recommending and ensuring flu vaccination for older adults. During this COCA Call, presenters will share easy-to-use education materials available to support HCPs in discussing flu prevention with older adult patients.

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Cognitive therapy and exposure therapy for hypochondriasis (health anxiety): A 3-year naturalistic follow-up.

Objective: Cognitive–behavioral therapy (CBT) has been shown to be effective in treating hypochondriasis. However, there are doubts regarding the long-term effectiveness of CBT for hypochondriasis, in particular for follow-up periods longer than 1 year. The aim of the present study was to evaluate the long-term effectiveness of cognitive therapy (CT) and exposure therapy (ET) for the treatment of hypochondriasis. Method: Seventy-five patients with a diagnosis of hypochondriasis who were previously treated with CT or ET were contacted 3 years after treatment. Fifty (67%) patients participated and were interviewed by an independent and blinded diagnostician using standardized interviews. Results: We found further improvements after therapy in primary outcome measures (d = .37), general functioning (d = .38), and reduced doctor visits (d = .30) during the naturalistic follow-up period. At the 3-year follow-up, 72% of the patients no longer fulfilled the diagnosis of hypochondriasis. Based on the main outcome measure, we found response rates of 76% and remission rates of 68%. At follow-up, only 4% of patients were taking antidepressant medication. Additional psychological treatment was utilized by 18% of the patients during the follow-up period (only 8% because of health anxiety). We found no overall differences between CT and ET. Only a trend for a greater deterioration rate in CT (13%) in comparison to ET (0%) was found. Conclusions: Our results suggest that ⅔ of the patients with hypochondriasis were remitted in the long term. Thus, remission rates after CBT were twice as high as in untreated samples. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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Mental disorders among undocumented Mexican immigrants in high-risk neighborhoods: Prevalence, comorbidity, and vulnerabilities.

Objective: This study aimed to: (a) provide population-based estimates for the prevalence of mental disorders, including substance use, among undocumented Mexican immigrants; (b) assess for relevant comorbidities; and (c) identify sociodemographic, immigration and contextual vulnerabilities associated with meeting criteria for a disorder. Method: This cross-sectional study used Respondent Driven Sampling (RDS) to collect and analyze data from clinical interviews with 248 undocumented Mexican immigrants residing near the California–Mexico border. The M.I.N.I. Mini International Neuropsychiatric Interview was used as the primary outcome of interest. For all analyses, inferential statistics accounted for design effects and sample weights to produce weighted estimates. Logistic regression was used in multivariate analyses. Results: Overall, 23% of participants met criteria for a disorder (95% CI = 17.1; 29.0). The most prevalent disorders were Major Depressive Disorder (14%, 95% CI = 10.2; 18.6), Panic Disorder (8%, 95% CI = 5.0; 11.9) and Generalized Anxiety Disorder (7%, 95% CI = 3.4; 9.8). Approximately 4% of participants met criteria for a substance use disorder (95% CI = 1.2; 6.1). After controlling for covariates, being 18 to 25 years and experiencing distress from postmigration living difficulties were significantly associated with meeting criteria for a disorder. Conclusion: Undocumented Mexican immigrants are an at-risk population for mental disorders, particularly depression and anxiety disorders. Given that distress from postmigration living difficulties is associated with meeting criteria for a disorder, revisiting policies and developing new alternatives to facilitate access and provision of context-sensitive mental health services for this population is necessary to protect the human rights of these immigrants and that of their U.S. families. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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PTSD symptoms predict outcome in trauma-informed treatment of intimate partner aggression.

Objective: This study sought to extend findings from a randomized controlled trial of the Strength at Home Men's Program (SAH-M) for intimate partner aggression (IPA) in military veterans by examining the impact of pretreatment posttraumatic stress disorder (PTSD) symptoms on treatment efficacy, and by examining new data on postintervention follow-up for individuals who received SAH-M after completing the enhanced treatment as usual (ETAU) wait-list control condition. Method: Using data from 125 male veterans who attended the SAH-M program immediately after an intake assessment or after waiting 6-month in the ETAU condition, this study used generalized linear modeling to examine predictors of physical and psychological IPA over a 9-month period of time. Results: PTSD symptoms at intake significantly predicted both physical and psychological IPA use, even after accounting for the effects of treatment condition, time, and number of sessions attended. PTSD had a strong association with both physical and psychological IPA. An interaction between PTSD and SAH-M was observed for psychological IPA but not physical IPA, and the magnitude of the effect was not clinically significant. There was a significant effect of SAH-M in reducing IPA in the full sample, including previously unanalyzed outcome data from the ETAU condition. Conclusion: The study results suggest that while SAH-M does not need to be modified to address the interaction between PTSD and treatment, outcomes could be enhanced through additional direct treatment of PTSD symptoms. Results extend prior analyses by demonstrating the effectiveness of SAH-M in reducing use of IPA in both the treatment and ETAU conditions. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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Markers for context-responsiveness: Client baseline interpersonal problems moderate the efficacy of two psychotherapies for generalized anxiety disorder.

Objective: To follow-up a randomized clinical trial that compared the acute and long-term efficacy of 15 sessions of cognitive–behavioral therapy (CBT) versus CBT integrated with motivational interviewing (MI) for severe generalized anxiety disorder (GAD; Westra, Constantino, & Antony, 2016), we (a) characterized the sample's baseline interpersonal problems, and (b) analyzed the role of several theory-relevant problems as moderators of the comparative treatment effects on outcome. Method: We first compared clients' (N = 85) baseline interpersonal problems profile to a general clinical sample. We next conducted piecewise, 2-level growth models to analyze the interactive effects of treatment condition and the hypothesized interpersonal problem indices of nonassertiveness (ranging from low to high), exploitability (ranging from low to high on this specific combination of nonassertiveness and friendliness), and overall agency (ranging from more problems of being too submissive to more problems of being too domineering, including friendly or hostile variants) on acute and follow-up worry reduction. Finally, we conducted hierarchical generalized linear models to examine these interactive effects on the likelihood of achieving clinically meaningful worry reduction across follow-up. Results: As expected, the GAD clients evidenced more nonassertive and exploitable interpersonal problems than the general clinical sample. Also as predicted, clients with more problematic nonassertiveness and low overall agency in their relationships had greater follow-up worry reduction in MI-CBT versus CBT, including to a clinically significant degree for the agency by treatment interaction. Conclusions: GAD-specific interpersonal problems can serve as contextual markers for integrative treatment selection and planning. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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Dispositional, demographic, and social predictors of trajectories of intimate partner aggression in early adulthood.

Objective: From a developmental systems perspective, the origins of maladjusted behavior are multifaceted, interdependent, and may differ at different points in development. Personality traits influence developmental outcomes, as do socialization environments, but the influence of personality depends on the socialization environment, and the influence of the socialization environment varies according to personality. The present study takes a developmental systems approach to investigate pathways through which dispositional traits in childhood might act in concert with peer and parental socialization contexts to predict trajectories of intimate partner aggression (IPA) during emerging adulthood. Method: The study included 466 participants (49% male, 81% European American, 15% African American) from a longitudinal study of social development. Measures of demographics, temperament, personality, parent–child relations, romantic relationships, peer relationships, and IPA were administered between 5 and 23 years of age. The study used latent growth curve analysis to predict variations in trajectories of IPA during early adulthood. Results: Numerous variables predicted risk for the perpetration of IPA, but different factors were associated at the end of adolescence (e.g., psychopathic traits) than with changes across early adulthood (e.g., friend antisociality). Males and individuals with a history of resistance to control temperament showed enhanced susceptibility to social risk factors, such as exposure to antisocial peers and poor parent-adolescent relations. Conclusions: Consistent with a developmental systems perspective, multiple factors, including personality traits in early childhood and aspects of the social environment in adolescence, predict trajectories of IPA during early adulthood through additive, mediated, and moderated pathways. Knowledge of these risk factors and for whom they are most influential could help inform efforts to prevent the emergence and persistence of IPA. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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Evaluation of an open-access CBT-based Internet program for social anxiety: Patterns of use, retention, and outcomes.

Objective: Internet-delivered cognitive–behavioral therapy (ICBT) has been established as both efficacious and effective in reducing symptoms of social anxiety. However, most research has been conducted in controlled settings, and little is known regarding the utility of such programs in an open-access format. The present study examined the use, adherence, and effectiveness of Joyable, an open-access, Internet-delivered, coach-supported CBT-based intervention for social anxiety. Method: Participants were 3,384 registered users (Mage [SD] = 29.82 [7.89]; 54% male) that created an account between 2014 and 2016. Characteristics of use, factors related to attrition and adherence, and within-group outcomes were examined. The primary outcome measure was the Social Phobia Inventory. Results: On average, participants remained in the program for 81.02 days (SD = 60.50), during which they completed 12.14 activities (SD = 11.09) and 1.53 exposures (SD = 3.18). About half (57%) had contact with a coach. Full adherence to the program was achieved by 16% of participants, a rate higher than previously published open-access studies of ICBT. Social anxiety symptoms were significantly reduced for participants that engaged in the program, with medium within-group effects from baseline through the cognitive restructuring module (d = 0.63–0.76) and large effects from baseline through the exposure module (d = 1.40–1.83). Response rates were high (72%). Exposures and coach contact were significant predictors of retention and outcome. Conclusions: This open-access online CBT-based program is effective in reducing social anxiety symptoms and has the potential to extend Internet-based mental health services to socially anxious individuals unwilling or unable to seek face-to-face evidence-based therapy. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

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Breast pseudoaneurysm arising from core needle biopsy should be left well alone

A 45-year-old woman previously fit and well, developed a pseudoaneurysm of the breast following core needle biopsy. She was ultimately reassured and discharged without further intervention. Pseudoaneurysm is a rare complication of core needle biopsy which, contrary to previously published cases, can be managed conservatively.

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Local Flap Technique After Removing Premaxilla for Closure of Oronasal Fistula.

This letter aimed to describe a surgical technique for oronasal fistula closure that promotes efficient healing and minimizes recurrence. The oronasal fistula was repaired by buccal flap. The technique proved to be simple and efficient. (C) 2017 by Mutaz B. Habal, MD.

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Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

Publication date: Available online 28 September 2017
Source:Cancer Cell
Author(s): Alan Mackay, Anna Burford, Diana Carvalho, Elisa Izquierdo, Janat Fazal-Salom, Kathryn R. Taylor, Lynn Bjerke, Matthew Clarke, Mara Vinci, Meera Nandhabalan, Sara Temelso, Sergey Popov, Valeria Molinari, Pichai Raman, Angela J. Waanders, Harry J. Han, Saumya Gupta, Lynley Marshall, Stergios Zacharoulis, Sucheta Vaidya, Henry C. Mandeville, Leslie R. Bridges, Andrew J. Martin, Safa Al-Sarraj, Christopher Chandler, Ho-Keung Ng, Xingang Li, Kun Mu, Saoussen Trabelsi, Dorra H'mida-Ben Brahim, Alexei N. Kisljakov, Dmitry M. Konovalov, Andrew S. Moore, Angel Montero Carcaboso, Mariona Sunol, Carmen de Torres, Ofelia Cruz, Jaume Mora, Ludmila I. Shats, João N. Stavale, Lucas T. Bidinotto, Rui M. Reis, Natacha Entz-Werle, Michael Farrell, Jane Cryan, Darach Crimmins, John Caird, Jane Pears, Michelle Monje, Marie-Anne Debily, David Castel, Jacques Grill, Cynthia Hawkins, Hamid Nikbakht, Nada Jabado, Suzanne J. Baker, Stefan M. Pfister, David T.W. Jones, Maryam Fouladi, André O. von Bueren, Michael Baudis, Adam Resnick, Chris Jones
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

Graphical abstract

Teaser

Mackay et al. perform an integrated analysis of >1,000 cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma. They identify co-segregating mutations in histone-mutant subgroups and show that histone wild-type subgroups are molecularly more similar to lower-grade tumors.


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Skin Regeneration with Self-Assembled Peptide Hydrogels Conjugated with Substance P in a Diabetic Rat Model

Tissue Engineering Part A , Vol. 0, No. 0.


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In Vitro Bioactivity of One- and Two-Dimensional Nanoparticle-Incorporated Bone Tissue Engineering Scaffolds

Tissue Engineering Part A , Vol. 0, No. 0.


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Identifying the Causes, Consequences, and Solutions to the Flint Water Crisis Through Collaborative Modeling

Environmental Justice , Vol. 0, No. 0.


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First Food Justice = Food Justice = Environmental Justice: A Call to Address Infant Feeding Disparities and the First Food System

Environmental Justice , Vol. 0, No. 0.


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Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): X. Pivot, S. Verma, L. Fallowfield, V. Müller, M. Lichinitser, V. Jenkins, A. Sánchez Muñoz, Z. Machackova, S. Osborne, J. Gligorov
AimTo assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166).Patients and methodsPost surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin^® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin^® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation.ResultsA total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients).ConclusionsThree-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected.



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Multidisciplinary team approach in the oral rehabilitation of patients with cleidocranial dysplasia to achieve a functional aesthetic outcome

Publication date: Available online 28 September 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): D. Patel, N. Patel, P.A. Brennan, J. Kwok
Cleidocranial dysplasia is a hereditary congenital disorder that results in delayed ossification of midline structures, and is caused by mutations in the RunX2 (runt-related transcription factor 2) gene located on the short arm of chromosome 6. Successful treatment depends on multidisciplinary assessment and a comprehensive staged treatment plan. We present a case series of 12 patients who were managed with a specifically tailored combination of surgery, orthodontics, and prosthodontics to provide a functional dentition and restore their smile and facial contour. Successful dental rehabilitation can be challenging in this group because patients often have multiple dental anomalies and a reduced quantity and density of alveolar bone. Rehabilitation with early intervention and a carefully planned multidisciplinary approach has been successful in the long term.



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Removal of a sequestrum by a patient with medication-related osteonecrosis of the jaw

Publication date: Available online 28 September 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Davies, A. Power, A. Kanatas




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Staging of squamous cell carcinoma of the tongue: extrinsic lingual muscles and the 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control staging manuals

Publication date: Available online 28 September 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A.W. Barrett, J.V. Tighe, A. Gulati, L. Newman, P.M. Norris, B.S. Bisase, M.K. Nicholls
Our aim was to find out first whether the extrinsic muscles of the tongue are histologically identifiable, and secondly to what degree the use of the new criteria in the 8th editions of the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control (UICC) manuals (which have recognised the importance of depth of invasion of tumour, rather than invasion of the extrinsic muscles of the tongue and extranodal extension), will alter staging of lingual squamous cell carcinoma (SCC). The histological sections from 165 patients who had had primary resection of lingual SCC were reviewed, and one or more extrinsic muscles of the tongue was identified in 100 patients (61%), with the genioglossus seen the most often (in 96). By contrast, the hyoglossus was identified in only eight patients, the styloglossus in two, and the palatoglossus in none. Identification was straightforward only in extensive resections. Applying the criteria from the 8th edition increased the number of pT3 SCC with a simultaneous reduction in pT4a tumours. The number of pN2b SCC was also reduced, but the new category of pN3b meant that overall 53% of tumours were upstaged. The kappa scores for agreement between the two sets of criteria were 0.221 (weighted 0.410) for the pT values, 0.508 (0.713) for pN values (but 0.227, weighted 0.386, if the pN0 values were removed before calculation), and 0.243 (0.514) for overall stage, indicating poor to fair agreement. We conclude that the removal of invasion of extrinsic muscles of the tongue as a criterion for a pT4a SCC is justified, and that many SCC of the tongue will be upstaged as a result of implementation of the 8th editions.



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Beneficial effect of botulinum toxin A on secondary ischaemic injury of skin flaps in rats

Publication date: Available online 28 September 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): L. Huang
Botulinum toxin A (BTX-A) protects against primary ischaemia of skin flaps, but its effect on secondary ischaemia is unknown. We induced secondary arterial or venous ischaemia in skin flaps of 32 Wistar rats, and tested the effectiveness of BTX injected subcutaneously 12hours before the flap was raised. The animals were divided into two groups of 16 (arterial or venous). Eight animals in each group were then treated with saline 1ml (control), and eight with BTX-A 5 IU (treatment). Ischaemia and necrosis were assessed after five days. There was no significant difference in necrosis between the two treatments in either group, but the amount of ischaemia did differ significantly (p=0.031 in the artetial ishcemia and p=0.015 in the venous ischemia group). BTX helped to salvage poor reperfusion in secondary ischaemia of skin flaps.



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Recurrent synovial chondromatosis of the temporomandibular joint: report of two cases

Publication date: Available online 28 September 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): Z.-X. Han, M.-J. Chen, C. Yang, M.-J. Dong
Synovial chondromatosis is the most common tumour-like lesion that is found in the temporomandibular joint (TMJ). Although it is benign and self-limiting, it can recur. We retrospectively reviewed 274 cases that were treated in our department from 2001-16 and found two recurrences, the radiological, surgical, histopathological, and follow-up results of which we report here. The reasons for their recurrence were analysed and elucidated.



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Correlation of the Iranian Voice Quality of Life Profile (IVQLP) with Acoustic Measurements across Three Common Voice Disorders

The Iranian Voice Quality of Life Profile (IVQLP) is a recent culture-based developed tool for assessing the quality of life of dysphonic patients. The research questions addressed here are as follows: (1) Are the correlations between IVQLP scores and values of objective voice measures? (2) Do the correlations differ across the three different voice disorders?

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Perceptual-Auditory and Acoustical Analysis of the Voices of Transgender Women

Voice is an important gender marker in the transition process as a transgender individual accepts a new gender identity. The objectives of this study were to describe and relate aspects of a perceptual-auditory analysis and the fundamental frequency (F0) of male-to-female (MtF) transsexual individuals. A case-control study was carried out with individuals aged 19–52 years who attended the Gender Identity Program of the Hospital de Clínicas of Porto Alegre. Vocal recordings from the MtF transgender and cisgender individuals (vowel /a:/ and six phrases of Consensus Auditory Perceptual Evaluation Voice [CAPE-V]) were edited and randomly coded before storage in a Dropbox folder.

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Haemodynamic Effects of Incomplete Stent Apposition in Curved Coronary Arteries

Publication date: Available online 27 September 2017
Source:Journal of Biomechanics
Author(s): Winson X. Chen, Eric K.W. Poon, Vikas Thondapu, Nicholas Hutchins, Peter Barlis, Andrew Ooi
Incomplete stent apposition (ISA, also known as malapposition) is a complication that affects day-to-day coronary stenting procedures. ISA is more prominent in complex arterial geometries, such as curvature, as a result of the limited conformability of coronary stents. These malapposed struts disturb the otherwise near-wall laminar blood flow and form a micro-recirculation environment. The micro-recirculation environment is often associated with low wall shear stress (WSS) and upsets the delicate balance of vascular biology, providing possible nidus for thrombosis and restenosis. In this study, a three-dimensional (3D) stent model was virtually deployed into an idealised curved coronary artery. Computational fluid dynamics (CFD) simulations were carried out to systematically analyse the haemodynamic effects of increasing maximum ISA distances, ranging from 180 (moderate), 400 (intermediate) to 910μm (severe) in an artery with decreasing radius of curvature (ROC). Micro-recirculations around both proximal and distal malapposed struts become more pronounced as compared to fully-apposed struts. The accompanying areas of low temporally-averaged WSS (AL-TAWSS) can increase two-fold compared to the fully-apposed condition. Furthermore, substantial regions (∼5.2% and 9.0%) of AL-TAWSS are detached from the distal end of the malapposed struts in both moderate and intermediate cases respectively. Malapposed stents also induce more variation of TAWSS at the inner bend of the artery. At the stent surface, maximum WSS increases three-fold from the fully-apposed case to intermediate ISA. High WSS on the strut surface is known to activate platelets which when exposed to the micro-recirculation environment may lead to their deposition and thrombosis.



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Fiber orientation effects in simple shearing of fibrous soft tissues

Publication date: Available online 27 September 2017
Source:Journal of Biomechanics
Author(s): Cornelius O. Horgan, Jeremiah G. Murphy
Fiber-reinforcement is a common feature of many soft biological tissues. Continuum mechanics modeling of the mechanical response of such tissues using transversely-isotropic hyperelasticity is now well developed. The fundamental deformation of simple shear within this framework is examined here. It is well known that the normal stress effect characteristic of nonlinear elasticity plays a crucial role in maintaining a homogeneous deformation state in the bulk of the specimen. Here we consider the effect of anisotropy and fiber-orientation on the shear and normal stresses. It is shown that the confining traction that needs to be applied to the top and bottom faces of a block in order to maintain simple shear can be compressive or tensile depending on the degree of anisotropy and on the angle of orientation of the fibers. In the absence of such an applied traction, an unconfined sample tends to bulge outwards or contract inwards perpendicular to the direction of shear so that one has the possibility of both a positive or negative Poynting effect. The results are illustrated using experimental data obtained by other authors for porcine brain white matter. The general results obtained here are relevant to the development of accurate shear test protocols for the determination of constitutive properties of fibrous biological soft tissues.



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In Vivo Repeatability of the Pulse Wave Inverse Problem in Human Carotid Arteries

Publication date: Available online 27 September 2017
Source:Journal of Biomechanics
Author(s): Matthew McGarry, Pierre Nauleau, Iason Apostolakis, Elisa Konofagou
Accurate arterial stiffness measurement would improve diagnosis and monitoring for many diseases. Atherosclerotic plaques and aneurysms are expected to involve focal changes in vessel wall properties; therefore, a method to image the stiffness variation would be a valuable clinical tool. The pulse wave inverse problem (PWIP) fits unknown parameters from a computational model of arterial pulse wave propagation to ultrasound-based measurements of vessel wall displacements by minimizing the difference between the model and measured displacements. The PWIP has been validated in phantoms, and this study presents the first in vivo demonstration. The common carotid arteries of five healthy volunteers were imaged five times in a single session with repositioning of the probe and subject between each scan. The 1D finite difference computational model used in the PWIP spanned from the start of the transducer to the carotid bifurcation, where a resistance outlet boundary condition was applied to approximately model the downstream reflection of the pulse wave. Unknown parameters that were estimated by the PWIP included a 10-segment linear piecewise compliance distribution and 16 discrete cosine transformation coefficients for each of the inlet boundary conditions. Input data was selected to include pulse waves resulting from the primary pulse and dicrotic notch. The recovered compliance maps indicate that the compliance increases close to the bifurcation, and the variability of the average pulse wave velocity estimated through the PWIP is on the order of 11%, which is similar to that of the conventional processing technique which tracks the wavefront arrival time (13%).



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Thyroid High-Impact Articles

FREE ACCESS through October 12, 2017.
Read now:

Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association

Clinical Implications of Immunoglobulin G4 to Graves' Ophthalmopathy
Sung Hoon Yu, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee

Idiopathic Low Ovarian Reserve Is Associated with More Frequent Positive Thyroid Peroxidase Antibodies
Chien-Wen Chen, Ya-Li Huang, Chii-Ruey Tzeng, Rui-Lan Huang, Chi-Huang Chen

Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with Changes in Acylcarnitine Levels
Mahmoud Al-Majdoub, Mikael Lantz, Peter Spégel

Defining Radioiodine-Refractory Differentiated Thyroid Cancer: Efficacy and Safety of Lenvatinib by Radioiodine-Refractory Criteria in the SELECT Trial
Naomi Kiyota, Bruce Robinson, Manisha Shah, Ana O. Hoff, Matthew H. Taylor, Di Li, Corina E. Dutcus, Eun Kyung Lee, Sung-Bae Kim, Makoto Tahara

Comparison of the Seventh and Eighth Editions of the American Joint Committee on Cancer/Union for International Cancer Control Tumor-Node-Metastasis Staging System for Differentiated Thyroid Cancer
Mijin Kim, Won Gu Kim, Hye-Seon Oh, Suyeon Park, Hyemi Kwon, Dong Eun Song, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Tae-Yon Sung, Min Ji Jeon

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

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Oxygen generating nanoparticles for improved photodynamic therapy of hypoxic tumours

Publication date: 28 October 2017
Source:Journal of Controlled Release, Volume 264
Author(s): Yingjie Sheng, Heather Nesbitt, Bridgeen Callan, Mark A. Taylor, Mark Love, Anthony P. McHale, John F. Callan
Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO2 nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO2 NPs were also observed to significantly increase tumour pO2 levels (p<0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO2 of 6.5mmHg in the period 10–30min following administration. A statistically significant improvement in PDT mediated efficacy (p<0.001) was also observed when the particles were administered to mice bearing the same tumours 20min prior to PDT treatment. These results suggest that the polymer coated CaO2 NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.

Graphical abstract

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Schwannoma of external auditory canal

Schwannomas of the external auditory canal are extremely rare and only a few cases have been reported in the literature. Herein, we report a case of schwannoma of the external ear canal in a 41-year male. Clinicians should consider the possibility that the schwannoma may originate in the external auditory canal mimicking other more frequently observed lesions.

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Electroneurography in the acute stage of facial palsy as a predictive factor for the development of facial synkinesis sequela

We investigated whether the value of ENoG is a predictive factor for the development of facial synkinesis in patients with facial palsy.

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Schwannoma of external auditory canal

Schwannomas of the external auditory canal are extremely rare and only a few cases have been reported in the literature. Herein, we report a case of schwannoma of the external ear canal in a 41-year male. Clinicians should consider the possibility that the schwannoma may originate in the external auditory canal mimicking other more frequently observed lesions.

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Electroneurography in the acute stage of facial palsy as a predictive factor for the development of facial synkinesis sequela

We investigated whether the value of ENoG is a predictive factor for the development of facial synkinesis in patients with facial palsy.

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Orthodontic camouflage versus orthodontic-orthognathic surgical treatment in class II malocclusion: a systematic review and meta-analysis

This systematic review was performed to compare dental, skeletal, and aesthetic outcomes between orthodontic camouflage and surgical-orthodontic treatment, in patients with a skeletal class II malocclusion and a retrognathic mandible who have already finished their growth period. A literature search was conducted, and a modified Downs and Black checklist was used to assess methodological quality. The meta-analysis was conducted using the DerSimonian–Laird random-effects method to obtain summary estimates of the standardized mean differences and corresponding 95% confidence intervals.

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Iodine-125 brachytherapy alone for advanced primary parotid gland carcinoma

This study aimed to evaluate the efficacy of iodine-125 (125I) brachytherapy alone for the treatment of advanced parotid gland carcinoma and to identify predictors of tumour control and patient survival. Primary parotid gland carcinoma patients (n=23) treated with 125I brachytherapy alone between 1 October 2005 and 31 July 2013 at Peking University Stomatology Hospital were enrolled in this retrospective study. All had clinical stage IV disease. The prescribed dose was 60–160Gy. The local control rate, survival rate, and predictors of the prognosis were evaluated.

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Stability of intraoral vertical ramus osteotomies for mandibular setback: a longitudinal study

This study aimed to investigate the postoperative longitudinal skeletal changes and stability following intraoral vertical ramus osteotomies (IVRO) for orthognathic mandibular setback, and the possible risk factors that might affect the stability. A retrospective cohort study was conducted. Lateral cephalograms were analyzed for the predictor (magnitude of setback and adjunctive procedures) and outcome (stability of vertical and horizontal dimensions) variables at six time points. A total of 152 patients (mean age 24.2 years) were included in the study.

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An Innovative Regenerative Endodontic Procedure Using Leukocyte and Platelet-rich Fibrin Associated with Apical Surgery: A Case Report

Regenerative endodontic procedures (REPs) associated with apical surgery could represent an alternative treatment strategy for patients whose teeth present incomplete root formation and extensive apical lesions. Leukocyte platelet-rich fibrin (L-PRF) has potential benefits in REPs; it could promote apical root formation and optimal bone healing. The aim of this case report was to describe innovative regenerative endodontic therapy using L-PRF in the root canal and an extensive apical lesion in an immature tooth with dens invaginatus and asymptomatic apical periodontitis.

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Revascularization-associated Intracanal Calcification: Assessment of Prevalence and Contributing Factors

Intracanal calcifications have been reported in endodontic cases after revascularization. The purpose of the current study was to determine the incidence of intracanal calcification and potential contributing factors in retrospective revascularization cases.

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Detecting Dentinal Microcracks Using Different Preparation Techniques: An In Situ Study with Cadaver Mandibles

This study assessed the frequency of dentinal microcracks using a cadaver mandible model in teeth instrumented with TRUShape (TS; Dentsply Sirona, York, PA), WaveOne Gold (WO, Dentsply Sirona), or K-files (KF) compared with an uninstrumented control group (CG).

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Researchers Develop Artificial Skin That Senses Touch

Researchers Develop Artificial Skin That Senses Touch Rachael Chacko '21 Artificial skin, developed by researchers at the University of Houston, allows a robot hand to distinguish between hot and cold temperatures. The image above is a simulated robotic hand. (Image Source: Pixabay) Researchers at the University of Houston have developed artificial […]

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The role of regulatory B cells in allergen immunotherapy.

Purpose of review: Allergen immunotherapy (AIT) is currently the only curative treatment available for allergic diseases, and has been used in clinical practice for over a century. Induction and maintenance of immune tolerance to nonhazardous environmental and self-antigens is essential to maintain homeostasis and prevent chronic inflammation. Regulatory B (BREG) cells are immunoregulatory cells that protect against chronic inflammatory responses primarily through production of anti-inflammatory cytokines such as IL-10, transforming growth factor-[beta], and IL-35. The importance of BREG cells has been extensively demonstrated in the context of autoimmune diseases. Data showing their role in the regulation of allergic responses are slowly accumulating. This review summarizes recent findings relevant to the topic of BREG cells and their potential role in AIT. Recent findings: BREG cells support AIT in models of allergic airway inflammation and intestinal inflammation through induction of regulatory T (TREG) cells. In humans BREG frequency increases during venom immunotherapy while the phenotype of allergen-specific B cells changes. Mechanisms of BREG-mediated tolerance to allergens include IL-10-mediated suppression of effector T cell, including TH2 responses, induction of TREG cells, IL-10-mediated inhibition of Dendritic cell maturation, modulation of T follicular helper responses, and production of anti-inflammatory IgG4 antibodies. Summary: Current evidence supports a potential role for BREG cells in induction and maintenance of allergen tolerance during AIT. A better understanding of the role of B cells and BREG cells in AIT could open potential new windows for developing targeted therapies specifically focused on promoting BREG responses during AIT. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comparing hemophagocytic lymphohistiocytosis in pediatric and adult patients.

Purpose of review: Hemophagocytic lymphohistiocytosis (HLH) has long been thought of primarily as a pediatric disease. However, this syndrome may occur secondary to underlying malignancies, infections, and autoimmune diseases, in adult patients. Here, we seek to highlight similarities and differences between pediatric and adult HLH, knowledge gaps, and areas of active research. Recent findings: Malignancy is a more frequent driver of HLH in adults, present in nearly half. Prognosis is poor as compared with nonmalignant HLH. Prognosis in adults is generally worse than pediatric patients, suggesting that age and other comorbid illnesses not surprisingly affect the outcome of HLH. Diagnostic and treatment approaches are more variable in adults, likely contributing to poorer outcomes. The frequency of mutations in HLH-causing genes is higher than had been anticipated in adults, although with a higher frequency of uniallelic and hypomorphic mutations than in children. Summary: Optimizing diagnostic criteria for earlier detection may benefit both children and adults. Standardizing treatment approaches in adults will be more difficult because of the variability in triggering illnesses, but a more standardized or algorithmic approach will likely be beneficial. More research into the role of uniallelic and hypomorphic mutations in adults is necessary, to understand treatment and prognostic implications. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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NLRC4 inflammasomopathies.

Purpose of review: The purpose of the review is to highlight developments in autoinflammatory diseases associated with gain-of-function mutations in the gene encoding NLR-family CARD-containing protein 4 (NLRC4), the NLRC4-inflammasomopathies. Recent findings: Three years since the identification of the first autoinflammation with infantile enterocolitis (AIFEC) patients, there is an improved understanding of how the NLRC4 inflammasome and interleukin 18 (IL-18) contribute to gut inflammation in myeloid and also intestinal epithelial cells. This information has opened new therapeutic avenues to treat AIFEC patients with targeted agents like recombinant IL-18 binding protein and antiinterferon-[gamma] antibodies. Additional phenotypes traditionally associated with NLRP3 mutations like familial cold autoinflammatory syndrome and neonatal onset multisystem inflammatory disease (NOMID), have now also been associated with gain-of-function NLRC4 mutations. Finally, NLRC4 somatic mosaicism has now been identified in a NOMID and an AIFEC patient, a finding emphasizing nontraditional modes of inheritance in autoinflammatory diseases. Summary: The NLRC4 inflammasomopathies constitute a growing autoinflammatory disease category that spans a broad clinical spectrum from cold urticaria to NOMID and the often fatal disease AIFEC. Rapid case identification with biomarkers like elevated serum IL-18 concentrations and early intervention with targeted immunomodulatory therapies are key strategies to improving outcomes for AIFEC patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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DGKζ ablation engenders upregulation of p53 level in the spleen upon whole-body ionizing radiation

Publication date: Available online 28 September 2017
Source:Advances in Biological Regulation
Author(s): Toshiaki Tanaka, Ken Iseki, Ken Tanaka, Tomoyuki Nakano, Mitsuyoshi Iino, Kaoru Goto
The tumor suppressor gene product p53, which coordinates the cellular response to various stresses, is subject to tight regulation by a complex network of signal transduction. The DGK family metabolizes lipidic second messenger diacylglycerol to produce phosphatidic acid. Our earlier studies showed that one isozyme, DGKζ, is involved in the regulatory mechanism of p53. In a cellular model of doxorubicin-induced DNA damage, overexpression of wild-type DGKζ suppresses p53 protein induction and reduces apoptosis, whereas knockdown of DGKζ upregulates p53 protein level and promotes apoptosis. Further examination reveals that DGKζ facilitates p53 degradation via ubiquitin-proteasome system in the cytoplasm. However, it remains undetermined whether the regulatory mechanism of DGKζ on p53 function found in cell-based experiments is also functional at the animal level. This study was conducted to elucidate this point using an experiment with DGKζ-KO mice under DNA damage induced by whole-body ionizing radiation. Our results reveal that p53 protein is induced robustly in the spleen of DGKζ-KO mice upon exposure to ionizing radiation, thereby promoting apoptosis in this organ. Taken together, the results demonstrate that DGKζ plays a sentinel role in p53 expression at the cellular and organismal levels after DNA damaging stress conditions.



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