bluuebunny/crossref_metadata_2025 huggingface dataset:
Public health and terrorism
Authors: Bhui Kamaldeep
Published: October 2018

This chapter describes terrorism and radicalization as processes that are usually managed by the criminal justice system, and erroneously applying information from convicted offenders to populations. Terrorism and radicalization are now proposed to be helpful targets of public health strategies, in order to shift potential risk factors and protective factors into more favourable profiles. Although the field is in its infancy, this chapter sets out some of the pros and cons of adopting a public health approach to tackle terrorism. Public health approaches to tackling violence are discussed, alongside research findings on how these might be adapted for tackling terrorism.
Resilience and well-being
Authors: Stewart-Brown Sarah
Published: October 2018

Resilience and well-being are relatively new to public health and psychiatry, and the research that underpins the concepts is often found in the publications of other disciplines—psychology, neuroscience, physiology, and philosophy. This chapter argues, using ideas from a range of disciplines, that resilience and well-being are integrally linked in that resilience is a product, a marker, and a developer of mental well-being. A level of well-being commensurate with a particular challenge enables a resilient response, and by enabling development in the face of the challenge, resilience enhances well-being. Both resilience and well-being are developmental and the key to successful development is a sensitive, attuned, and trusting relationship, which conditions the self-regulation response. Approaches to enhancing resilience and well-being are therefore very similar. They start with relational support in infancy and childhood, and carry on throughout the life course, with activities and programmes that support the development of self–regulation.
Telemental health
Authors: Waugh Maryann , Mishkind Matthew , Shore Jay H.
Published: October 2018

Telemental health is a term for health care that leverages audio and video telecommunications technologies such as video-teleconferencing, computers, mobile devices, the Internet, telephones, and broadband connectivity to provide mental health services across time and physical distance. Telemental health has the capacity to make a significant and positive impact on public mental health by its ability to not only increase access to care, but also more effectively tailor mental health services to individual or community-wide healthcare needs. This chapter describes ways that telemental health is currently being used to impact mental health promotion, prevention, and treatment, summarizes the evidence base for these applications, and highlights some practical considerations for providers and systems implementing this newer virtual care delivery system.
Managing research and evaluation for public mental health
Authors: Stewart-Brown Sarah
Published: October 2018

Public mental health is a new and interdisciplinary subject and as such demands thorough research and evaluation. The disciplines involved use different approaches to research and would benefit from cooperative working. But, especially when researching unfamiliar territory like that of public mental health, each discipline prefers the reassurance of its tried and tested methods, making cooperation more challenging. And many existing research methods that have proved so valuable in public health and social science because they are good at identifying single causes for a single problem are inadequate in the face of the complex systems with multiple interacting causes and consequences, which determine public mental health. This chapter looks at some of the research methods used in public mental health and identifies the strengths and limitations of these methods for advancing knowledge in this field.
Conclusion
Authors: Bhugra Dinesh , Bhui Kamaldeep , Wong Samuel Y. S. , Gilman Stephen E.
Published: October 2018

Positive mental health can contribute to better educational, employment, and social functioning. Public mental health includes both mental health promotion and prevention of mental ill health. Public mental health works at levels of general and whole population and society, vulnerable groups and individuals, and those needing early diagnosis and intervention. At each level different strategies are required. It is recognized that, when in distress, most individuals will seek help first from within their personal, social, and folk support systems and seek professional help only if that does not work. This depends upon healthcare systems and available resources. In this chapter the editors propose that public mental health is an important part of any healthcare system and suggest ways forward. They recognize that there is research evidence confirming the value of mental health promotion through education and empowerment, and by promoting strength and resilience through various local and national activities
Cholesteatoma surgery
Authors: Aldren Christopher
Published: October 2018

This chapter discusses Toner and Smyth’s paper on cholesteatoma including the design of the study (outcome measures, results, conclusions, and a critique).
Retraction pockets
Authors: Selvadurai David , Oikonomou Georgios
Published: October 2018

This chapter discusses Nankivell and Pothier’s paper on surgery for tympanic membrane retraction pockets including the design of the study (outcome measures, results, conclusions, and a critique).
Imaging cholesteatoma
Authors: Whiteside Olivia
Published: October 2018

This chapter discusses Jindal, Riskalla, Jiang, Conor, and Fitzgerald O’Conor’s paper on cholesteatoma imaging including the design of the study (including outcome measures, results, conclusions, and a critique).
Otoacoustic emissions
Authors: Keaton Casie
Published: October 2018

This chapter discusses Kemp, Ryan, and Bray’s 1990 paper on the effective use of otoacoustic emissions including the design of the study (outcome measures, results, conclusions, and a critique).
A neurophysiological model of tinnitus
Authors: McFerran Don
Published: October 2018

This chapter discusses Jastreboff and Hazell’s 1993 paper on a neurophysiological model of tinnitus including the design of the study (outcome measures, results, conclusions, and a critique).
Endolymphatic sac decompression
Authors: Kutz Walter
Published: October 2018

This chapter discusses Thomsen, Bretlau, Tos, and Johnsen’s 1981 paper on Ménière’s disease and endolymphatic sac decompression compared with sham (placebo) decompression including the design of the study (outcome measures, results, conclusions, and a critique).
Semicircular canal dehiscence
Authors: Lambert Paul
Published: October 2018

This chapter discusses Minor, Solomon, Zihreich, and Zee’s 1998 paper on semicircular canal dehiscence including the design of the study (outcome measures, results, conclusions, and a critique).
Histopathological aspects of presbyacusis
Authors: Lambert Paul , Dubno Judy
Published: October 2018

This chapter discusses Schuknecht and Gacek’s 1993 paper on histopathological aspects of presbyacusis including the design of the study (outcome measures, results, conclusions, and a critique).
Sudden sensorineural hearing loss
Authors: Lambert Paul , Hatch Jonathan
Published: October 2018

This chapter discusses papers on sudden sensorineural hearing loss including the design of the studies (outcome measures, results, conclusions, and a critique).
Assessing quality of life in rhinosinusitis
Authors: Hopkins Claire
Published: October 2018

This chapter discusses Piccirillo, Merritt, and Richards’s 2002 paper on the psychometric and clinimetric validity of the 20-item Sino-Nasal Outcome Test (SNOT-20) including the design of the study (outcome measures, results, conclusions, and a critique).
Allergic fungal rhinosinusitis
Authors: Saleh Hesham , Ahmed Jahangir
Published: October 2018

This chapter discusses Bent and Kuhn’s paper on the diagnosis of allergic fungal sinusitis including the design of the study (outcome measures, results, conclusions, and a critique).
Non-infectious, non-allergic rhinitis
Authors: Reid Luke
Published: October 2018

This chapter discusses Sanico and Togias’s paper on non-infectious, non-allergic rhinitis including the design of the study (outcome measures, results, conclusions, and a critique).
Smell and taste disorders
Authors: Erskine Sally
Published: October 2018

This chapter discusses Deems, Doty, Settle, Moore-Gillon, Shaman, Mester, Kimmelman, Brightman, and Snow’s paper on smell and taste disorders including the design of the study (outcome measures, results, conclusions, and a critique).
Body dysmorphic disorder
Authors: Field Rebecca
Published: October 2018

This chapter discusses Veale, De Haro, and Lambrou’s paper on body dysmorphic disorder including the design of the study (outcome measures, results, conclusions, and a critique).
The classification of orbital complications of acute rhinosinusitis
Authors: Bhalla Rajiv
Published: October 2018

This chapter discusses Chandler, Langenbrunner, and Stevens paper on the classification of orbital complications of acute rhinosinusitis including the design of the study (outcome measures, results, conclusions, and a critique).
Oncological management of head and neck cancer I
Authors: Masterson Liam
Published: October 2018

This chapter discusses Department of Veterans Affairs Laryngeal Cancer Study Group’s paper on oncological management of head and neck cancer including the design of the study (outcome measures, results, conclusions, and a critique).
Incidence of thyroid cancer
Authors: Roques Tom
Published: October 2018

This chapter discusses Davies and Welch’s paper on the incidence of thyroid cancer including the design of the study (outcome measures, results, conclusions, and a critique).
Paediatric sensorineural hearing loss
Authors: Kennedy Veronica
Published: October 2018

This chapter discusses Morzaria, Westerberg, and Kozak’s paper on paediatric sensorineural hearing loss including the design of the study (outcome measures, results, conclusions, and a critique).
Congenital malformations of the inner ear
Authors: Kennedy Veronica
Published: October 2018

This chapter discusses Jackler, Luxford, and Hous’s paper congenital malformations of the inner ear including the design of the study (outcome measures, results, conclusions, and a critique).
Cochlear implantation in children
Authors: Selvadurai David , Oikonomou Georgios
Published: October 2018

This chapter discusses O’Donoghue, Nikolopoulos, and Archbold’s paper on cochlear implantation in children including the design of the study (outcome measures, results, conclusions, and a critique).
The cricoid split
Authors: Morrison Gavin
Published: October 2018

This chapter discusses Cotton and Seid’s paper on the cricoid split including the design of the study (outcome measures, results, conclusions, and a critique).
Infantile capillary haemangiomas
Authors: Saunders Mike
Published: October 2018

This chapter discusses Léauté-Labrèze, Dumas de la Roque, Hubiche, Boralevi, Thambo, and Taïeb’s paper on propranolol for severe haemangiomas of infancy including the design of the study (outcome measures, results, conclusions, and a critique).
Classification of fasciocutaneous flaps
Authors: Haywood Richard
Published: October 2018

This chapter discusses Cormack and Lamberty’s paper on classification of fasciocutaneous flaps including the design of the study (outcome measures, results, conclusions, and a critique).
Vascular territories
Authors: Haywood Richard
Published: October 2018

This chapter discusses Taylor and Palmer’s paper on the vascular territories including the design of the study (outcome measures, results, conclusions, and a critique).
The free thigh flap
Authors: Haywood Richard
Published: October 2018

This chapter discusses Song, Chen, and Song’s paper on the free thigh flap including the design of the study (outcome measures, results, conclusions, and a critique).
Effects of general anaesthesia in children
Authors: Hodgson Phil
Published: October 2018

This chapter discusses Davidson et al.’s paper on the effects of general anaesthesia in children including the design of the study (outcome measures, results, conclusions, and a critique).
Bolitho v. City & Hackney Health Authority
Authors: Webber Peter
Published: October 2018

This chapter discusses the legal case between Bolitho v. City & Hackney Health Authority [1996], including the detail of the case and its implications.
What is the clinical relevance of the Numerical rating scale for pain?
Authors: Cox Felicia
Published: October 2018

The landmark paper discussed in this chapter is ‘Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale’, published by Farrar et al. in 2001. The numerical rating scale is now the standard instrument used in chronic pain studies to measure pain intensity. Farrar et al. determined the changes in pain intensity that were clinically significant for studies of chronic pain while measuring the patient’s global impression of change. The paper used pooled data from ten recent studies of pregabalin in 2,724 subjects. The authors reported a consistent relationship between pain intensity and patient global impression of change, regardless of study, disease type, age, sex, study result, or treatment group. A reduction of approximately two points on the numerical rating scale, or of 30% in the global impression of change of pain intensity, represented a clinically important difference.
Identification of hypocrealean reptile pathogenic isolates with MALDI-TOF MS
Authors: Schneider Juliane , Heydel Tilo , Pees Michael , Schrödl Wieland , Schmidt Volker
Published: October 2018

Biotyper analysis of Nannizziopsis guarroi, a fatal fungal pathogen in lizards, was described recently. Hypocrealean fungal infections in captive reptiles appear with an increasing frequency during the last decade. Therefore, the aim of this study was to proof Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) as diagnostic tool for the identification of reptile pathogenic hypocrealean fungi. Ten fungal isolates obtained from nine reptiles with fungal glossitis, disseminated visceral mycosis, pneumomycosis, and fungal keratitis were analyzed. Phylogeny consisted of fragments of the large subunit of nuclear encoded ribosomal DNA (D1/D2, LSU) and the internal transcribed spacer region 1 of nuclear encoded ribosomal DNA (ITS1) as well as the protein coding gene translation elongation factor 1 alpha (TEF). Results revealed unanimously two Metarhizium granulomatis genotypes in a total of three isolates, various M. viride genotypes (n = 3), two different Purpureocillium lilacinum isolates as well as one isolate of each P. lavendulum and Beauveria bassiana. Purpureocillium lilacinum and B. bassiana are likewise frequently employed as a mycoinsecticide and mycoacaricide in agriculture on a worldwide scale and have occasionally been reported in man, causing fungal keratitis, sclerokeratitis, nosocomial infections in immunosuppressed patients, as well as cavitary pulmonary disease and cutaneous hyalohyphomycosis in immunocompetent patients. According to the results establishment of Biotyper analysis for faster differentiation of reptile-associated fungal pathogens is entirely justified.
Impaired urinary concentration ability is a sensitive predictor of renal disease progression in Joubert syndrome
Authors: Nuovo Sara , Fuiano Laura , Micalizzi Alessia , Battini Roberta , Bertini Enrico , Borgatti Renato , Caridi Gianluca , D’Arrigo Stefano , Fazzi Elisa , Fischetto Rita , Ghiggeri Gian Marco , Giordano Lucio , Leuzzi Vincenzo , Romaniello Romina , Signorini Sabrina , Stringini Gilda , Zanni Ginevra , Romani Marta , Valente Enza Maria , Emma Francesco
Published: October 2018

Background

Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain–hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25–30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS.

Methods

Renal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time.

Results

At last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels <600 mOsm/kg H2O, and significantly increased in patients with an early diagnosis of isolated UCD.

Conclusions

We conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.
Microsurgical Resection of Anaplastic Ependymoma of the Cerebellopontine Angle in an Adult: 3-Dimensional Operative Video
Authors: Sayyahmelli Sima , Baskaya Mustafa K
Published: October 2018

Infratentorial ependymomas usually arise in the fourth ventricle and extend into the cerebellopontine angle (CPA) through the foramina of Luschka is well described. A primary CPA location of an ependymoma is distinctly uncommon.

 In this 3-dimensional video, we present a 38-yr-old woman with a 1-mo history of vertigo and slow left sided gaze drift. She underwent microsurgical gross total resection of the CPA ependymoma via retrosigmoid approach. The histopathology was grade III anaplastic ependymoma. She tolerated the surgery well and her postoperative course was uneventful. She received radiation therapy and there was no recurrent disease in follow-up studies.

 Important steps of the surgical approach and microsurgical techniques in resection of these challenging tumors are demonstrated in this 3-dimensional surgical video. The patient consented to publication of her image.
A Pilot Comparison of Multispectral Fluorescence to Indocyanine Green Videoangiography and Other Modalities for Intraoperative Assessment in Vascular Neurosurgery
Authors: Nickele Chris , Nguyen Vince , Fisher Winfield , Couldwell William , Aboud Emad , David Carlos , Morcos Jacques , Charalampaki Cleopatra , Arthur Adam
Published: October 2018

BACKGROUND

Digital subtraction angiography (DSA) is the gold standard for vascular imaging, but is not easily integrated into a continuous microsurgical environment. Other available modalities for intraoperative vascular assessment have their own limitations.

OBJECTIVE

To investigate multispectral fluorescence (MFL), a new technology based on indocyanine green (ICG) fluorescence, which may provide advantages over current intraoperative imaging modalities.

METHODS

Cadaveric intracranial aneurysm models and turkey wing bypasses were created and tested with white light and micro-Doppler ultrasound, indocyanine green videoangiography (ICG-VA), MFL, and DSA in conditions mimicking surgery. Assessments with these modalities were scored by 7 neurosurgeons.

RESULTS

DSA was significantly better than other modalities in evaluating the vasculature (P < .0001), but was significantly less ergonomic and efficient (P < .0001). MFL and ICG-VA were not significantly different from each other. Both were significantly better than white light/micro-Doppler ultrasound in assessing occlusion and patency (P ≤ .011), and both were better than DSA in ergonomics and efficiency (P < .0001).

CONCLUSION

MFL performs similarly to ICG-VA in a laboratory setting. Further study will be required to determine whether it compares favorably in the operating room. While DSA is the standard for cerebrovascular visualization, MFL and ICG are significantly more ergonomic and efficient.
Implantation of a Thoracic Spinal Cord Stimulator Paddle Electrode and Generator Under General Anesthesia With Intraoperative Neuromonitoring: 2-Dimensional Operative Video
Authors: Stone Lauren E , Falowski Steven M
Published: October 2018

Spinal cord stimulation is a well-established and effective therapy in the treatment of pain. Proper patient selection and accurate lead placement are paramount in its success. Placement is a multifaceted process requiring proper paddle placement, a well thought out generator placement and appropriate means to limit complications and enhance success. Several intraoperative techniques maximize outcomes, including removal of the superior portion of the inferior level's spinous process for paddle access into the epidural space, generator pocket placement in a location that limits patient discomfort, a strain relief loop at the thoracic incision to prevent lead fractures and allow for full spinal flexibility, generator placement parallel to the body and secured in the pocket to prevent unwanted movement, and intraoperative neuromonitoring for patient comfort and more accurate lead placement compared to X-ray alone or awake placement. This case demonstrates these key elements of intraoperative technique in a candidate with the most common indication for spinal cord stimulator placement–postlaminectomy syndrome–underscoring the ease and viability of this procedure in the appropriate patient population in a means that reduces future complications and adverse events while maximizing success.

 Full patient consent for video-recording and subsequent use for research purposes was attained. All patient identifiers have been removed for the purpose of patient confidentiality.
Resection of an Embolized Cirsoid Aneurysm With Intracranial Venous Drainage: 2-Dimensional Operative Video
Authors: Heiferman Daniel M , Syed Hasan R , Li Daphne , Rothstein Brian D , Shaibani Ali , Tomita Tadanori
Published: October 2018

Cirsoid aneurysms, also known as scalp arteriovenous malformations (AVM), are rare congenital extracranial vascular anomalies that often present as an enlarging pulsatile scalp mass. A 14-yr-old male presented with a pulsatile scalp lesion that was first noticed 3 yr prior and had progressively enlarged. No history of trauma was reported. MRI demonstrated a 4 cm wide and 2 cm tall nidus and catheter angiography was performed to further define the vascular supply and drainage. The patient underwent transvenous endovascular embolization followed by surgical excision via a bicoronal incision, as shown in this operative video. Care was taken to identify, cauterize, and transect feeding vessels from the superficial temporal, supratrochlear, and supraorbital arteries circumferentially to completely devascularize and resect the galeal nidus from overlying scalp tissue and underlying pericranium. Previously unreported in the literature, transosseous emissary veins partially draining the lesion were noted on angiography and were waxed thoroughly during surgery. Six-month follow-up examination demonstrated a well-healed incision without evidence of AVM recurrence. The unique venous drainage of this cirsoid aneurysm highlights the value of diagnostic angiography to fully characterize these rare and complex vascular lesions prior to pursuing definitive treatment.

 IRB approval was obtained from the Ann & Robert H. Lurie Children's Hospital of Chicago Institutional Review Board (IRB #2018-1799). The IRB waives the requirement of obtaining informed consent for this study in accordance with 45 CFR 46.116(d).
Microsurgery of Spinal Dural Arteriovenous Fistula Using Indocyanine Green Video Angiography: 2-Dimensional Operative Video
Authors: Yokoyama Kunio , Okuda Yasuaki , Yamada Makoto , Tanaka Hidekazu , Ito Yutaka , Yamashita Masashi , Sugie Akira , Kawanishi Masahiro
Published: October 2018

Spinal dural arteriovenous fistulas (SDAVF) develop by direct abnormal arteriovenous connection between both sides of the spinal dura matter. In this condition, there is no intervening nidus between a meningeal segmental artery and a radiculomedullary vein. Open microsurgery is one of the choices for patients with SDAVF. When the AVF is on the inner dural surface, we can easily block the radiculomedullary vein in a microscopic view. We herein report a 50-yr-old woman who presented with low back pain, was diagnosed with an SDAVF, and underwent surgical treatment under a microscopic view. The spinal angiography demonstrated abnormal arteriovenous connections between intercostal arteries at the level of Th11 to 12 and the intradural radiculomedullary vein. Operative indocyanine green (ICG) microangiography demonstrated the blood flow in meningeal vessels and their anastomoses between both sides of the dural surface. We easily identified the radiculomedullary vein fed by the surrounding meningeal feeding arteries and block completely under a direct microscopic view. We detected the change in hemodynamic during feeder ligation by Flow 800 (Zeiss Penteto Flow 800 microscope; Zeiss Corporation, Tokyo, Japan). After surgery, the patient's symptoms disappeared and no recurrence of the disease has been noted in the past 23 mo. We have received the informed consent of this patient for the publication of this case report.
Use of an Ecological Momentary Assessment Application to Assess the Effects of Auricular Point Acupressure for Chronic Low Back Pain
Authors: Lin Wei-Chun , Burke Lora , Schlenk Elizabeth A. , Yeh Chao Hsing
Published: October 2018

The purpose of this pilot study was to assess the feasibility and usability of an ecological momentary assessment smartphone application. The app collected real-time data on chronic low back pain and time-contingent ecological momentary assessment surveys during a 4-week auricular point acupressure intervention, and on the consistency between recalled and momentary clinical measures. Eighteen participants received auricular point acupressure treatment weekly for 4 weeks. Each participant was provided a smartphone with the ecological momentary assessment application installed, along with instructions for use. The primary outcomes comprised pain intensity, pain interference with daily activity, sleep quality score, and medication usage. System Usability Scale and adherence were also measured. According to the results, the rate of adherence for completion of the random ecological momentary assessment survey was 87%. The usability score for the ecological momentary assessment application was reported as 78. The average recalled pain intensity was higher than the mean momentary pain intensity. Self-reported average pain interference with daily activities showed a similar result. Spearman rank correlation coefficients were greater than +0.70; P < .01 for the associations among recalled and momentary measurements. In conclusion, the study demonstrated promising adherence rates and supported the usability and feasibility of using an ecological momentary assessment application on a smartphone to collect real-time data on chronic lower back pain, which eliminated recall bias.
Nonparticipation Selection Bias in the MOBI-Kids Study
Authors: Turner Michelle C. , Gracia-Lavedan Esther , Momoli Franco , Langer Chelsea E. , Castaño-Vinyals Gemma , Kundi Michael , Maule Milena , Merletti Franco , Sadetzki Siegal , Vermeulen Roel , Albert Alex , Alguacil Juan , Aragones Nuria , Badia Francesc , Bruchim Revital , Carretero Gema , Kojimahara Noriko , Lacour Brigitte , Morales-Suarez-Varela Maria , Radon Katja , Remen Thomas , Weinmann Tobias , Yamaguchi Naohito , Cardis Elisabeth
Published: October 2018

Background:

MOBI-Kids is a 14-country case–control study designed to investigate the potential effects of electromagnetic field exposure from mobile telecommunications devices on brain tumor risk in children and young adults conducted from 2010 to 2016. This work describes differences in cellular telephone use and personal characteristics among interviewed participants and refusers responding to a brief nonrespondent questionnaire. It also assesses the potential impact of nonparticipation selection bias on study findings.

Methods:

We compared nonrespondent questionnaires completed by 77 cases and 498 control refusers with responses from 683 interviewed cases and 1501 controls (suspected appendicitis patients) in six countries (France, Germany, Israel, Italy, Japan, and Spain). We derived selection bias factors and estimated inverse probability of selection weights for use in analysis of MOBI-Kids data.

Results:

The prevalence of ever-regular use was somewhat higher among interviewed participants than nonrespondent questionnaire respondents 10–14 years of age (68% vs. 62% controls, 63% vs. 48% cases); in those 20–24 years, the prevalence was ≥97%. Interviewed controls and cases in the 15- to 19- and 20- to 24-year-old age groups were more likely to have a time since start of use of 5+ years. Selection bias factors generally indicated a small underestimation in cellular telephone odds ratios (ORs) ranging from 0.96 to 0.97 for ever-regular use and 0.92 to 0.94 for time since start of use (5+ years), but varied in alternative hypothetical scenarios considered.

Conclusions:

Although limited by small numbers of nonrespondent questionnaire respondents, findings generally indicated a small underestimation in cellular telephone ORs due to selective nonparticipation.
Lifestyle Patterns and Survival Following Breast Cancer in the Carolina Breast Cancer Study
Authors: Parada Humberto , Sun Xuezheng , Tse Chiu-Kit , Olshan Andrew F. , Troester Melissa A.
Published: October 2018

Background:

Few studies have examined the impact of lifestyle patterns on survival following breast cancer. We aimed to identify distinct lifestyle patterns based on five behavior/dietary exposures among a population-based sample of women diagnosed with breast cancer and to examine their association with subsequent survival.

Methods:

In the Carolina Breast Cancer Study Phases I/II, we interviewed 1,808 women 20–74 years of age following diagnosis of invasive breast cancer. We determined vital status using the National Death Index (717 deaths, 427 from breast cancer; median follow-up 13.56 years). We assessed lifestyle patterns using a latent class analysis based on five behavioral and dietary exposures: current versus never/former smokers; low versus high vegetable and fruit intake; high and low/moderate, versus no alcohol consumption; and no and low/moderate, versus high regular physical activity. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, and cause-specific and subdistribution HRs for breast cancer–specific mortality within 5 years and 13 years postdiagnosis conditional on 5-year survival.

Results:

We identified three distinct lifestyle patterns: healthy behavior and diet (n = 916); healthy behavior and unhealthy diet (n = 624); and unhealthy behavior and diet (n = 268). The unhealthy (vs. healthy) behavior and diet pattern was associated with a 13-year conditional all-cause mortality HR of 1.4 (95% CI = 1.1, 1.9) and with 13-year conditional breast cancer–specific and subdistribution HRs of 1.2 (95% CI = 0.79, 1.9) and 1.2 (95% CI = 0.77, 1.8), respectively.

Conclusions:

Behavioral and dietary patterns can be used to identify lifestyle patterns that influence survival patterns following breast cancer diagnosis.
The Utilization of Interventional Radiologic Procedures in the Surgical Management of Placenta Accreta Syndrome
Authors: SHRIVASTAVA VINEET K. , NAGEOTTE MICHAEL P.
Published: October 2018

The role of Interventional radiologic procedures for the management of suspected placenta accreta spectrum (PAS) has evolved considerably over last 3 decades. In this article, the authors describe the various techniques of vascular occlusion for the management of PAS and provide a brief review of the literature examining the pros and cons in the use of these devices.
Optimizing therapy in carbapenem-resistant Enterobacteriaceae infections
Authors: Tumbarello Mario , Losito Angela Raffaella , Giamarellou Helen
Published: October 2018

Purpose of review

In the absence of randomized clinical trial data, questions remain regarding the optimal treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections. CRE have historically been susceptible to polymyxins, tigecycline or aminoglycosides (mostly gentamicin), and these antibiotics have long been considered the drugs of choice for CRE infections, although varying rates of resistance to all have been reported. This review looks at data from clinical studies assessing the outcomes of CRE infections treated with different antibiotic regimens.

Recent findings

The recently approved fixed-dose combination agent, ceftazidime-avibactam (CAZ-AVI), is active against KPC and OXA-48-producing Enterobacteriaceae. The limited clinical data available on CAZ-AVI indicate that it is associated with survival benefits relative to other commonly used regimens, although development of resistance is a concern. New drugs active against CRE isolates (including the recently approved meropenem-vaborbactam) are in different stages of development.

CAZ-AVI and meropenem-vaborbactam seem destined to become the backbone of target therapy for high-risk patients with severe infections caused by susceptible CRE strains. However, empirical therapy should be based on risk factors to be defined in the near future, whereas the necessity of combinations with CAZ-AVI requires further studies. Polymyxins are still important options for low-risk patients with susceptible CRE infections, but also for high-risk patients in regions where metallo-β-lactamase-producing CRE predominate because CAZ-AVI and meropenem-vaborbactam are both ineffective against these strains.
Polyclonal and monoclonal antibodies for the treatment of influenza
Authors: Beigel John H.
Published: October 2018

Purpose of review

This review summarizes past and ongoing efforts for using polyclonal and monoclonal antibodies for the treatment of influenza, and is focused on products that have entered clinical trials.

Recent findings

At least three polyclonal and eight monoclonal antibody products have been tested in clinical trials for the treatment of influenza. Considered across the two classes of therapeutics, these products appear to be safe and well tolerated. However, the efficacy results have been mixed and inconclusive. To date, no products have consistently shown superiority to currently available antivirals.

No products within these two classes have been licensed, and several products appear to have stopped further clinical development. There are several ongoing studies that are anticipated to be completed or reported in the next 1–2 years which will be critical for understanding the value of polyclonal and monoclonal antibodies in the treatment of influenza.
Remote Intestinal Injury Early After Experimental Polytrauma and Hemorrhagic Shock
Authors: Wrba Lisa , Ohmann Julia J. , Eisele Philipp , Chakraborty Shinjini , Braumüller Sonja , Braun Christian K. , Klohs Bettina , Schultze Anke , von Baum Heike , Palmer Annette , Huber-Lang Markus , Halbgebauer Rebecca
Published: October 2018

Dysfunction of the gut–blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein.

Male C57BL/6 mice were subjected to either PT (thorax trauma, closed head injury, soft tissue injury, and distal femoral fracture), 60 min of pressure-controlled HS (30 ± 5 mmHg), or PT+HS, or sham procedures.

Animals of all trauma groups showed an increase in abdominal girth and dilation of the intestine during the experimental period, which was largest in the PT+HS group. Increased blood–tissue permeability to albumin (assessed by Evans blue dye) was found in the HS group. Experimental groups showed a slight increase in plasma concentration of intestinal fatty acid binding protein and some intestinal damage was histologically detectable. Of note, PT+HS animals revealed significantly reduced expression of ZO-1 in intestinal epithelial cells. In an in-vitro model, stimulation of human colon epithelial cells with peptidoglycan, but not with lipopolysaccharide, resulted in elevated secretion of pro-inflammatory cytokines, reflecting inflammatory activity of the intestinal epithelium.

Taken together, PT and HS lead to increased permeability of the gut–blood barrier. Bacterial components may lead to production of inflammatory and chemotactic mediators by gut epithelial cells, underlining the role of the gut as an immunologically active organ.
Endpoints in clinical trials in cancer cachexia: where to start?
Authors: Laird Barry J.A. , Balstad Trude R. , Solheim Tora S.
Published: October 2018

Purpose of review

The lack of agreement and knowledge of optimal endpoints in cachexia trials have impeded progress in finding interventions counteracting the devastating effects cancer cachexia has on morbidity and mortality. An endpoint should both be sensitive enough to detect change and specific enough not to be influenced by other conditions or treatments.

Recent findings

There is a wealth of potential and applied endpoints in trials investigating cachexia. As of today, there is no generally acknowledged consensus, but assessments of key factors such as body composition should continue to be applied. However, the impact and effect size necessary to achieve clinical benefit using these endpoints are not clear. Further, the use of other endpoints assessing physical function, symptom evaluation and quality of life remains to be elucidated.

It is essential that endpoints are clinically relevant and further research is therefore needed to develop endpoints that are meaningful for patients with cachexia.
Experimental and Computational Evidence for Self-Assembly of Mitochondrial UCP2 in Lipid Bilayers
Authors: Ardalan A. , Uwumarenogie S. O. , Fish M. , Sowlati-Hashjin S. , Karttunen M. , Smith M. D. , Jelokhani-Niaraki M.
Published: October 2018

Uncoupling proteins (UCPs) are members of the mitochondrial carrier family (MCF) that transport protons across the inner mitochondrial membrane, thereby uncoupling electron transport from ATP synthesis. The stoichiometry of UCPs, and the possibility of co-existence of this protein as mono-meric and associated forms in lipid membranes remain an intriguing open question. In the current study, the tertiary structure of UCP2 was analyzed both experimentally and through molecular dynamics (MD) simulations. After recombinant expression of UCP2 in the inner membrane of E. coli, the protein was directly extracted from the bacterial membranes with a non-denaturing detergent and purified both as a pure monomer and as a mixture of monomers, dimers and tetramers. Both protein preparations were re-constituted in egg yolk lipid vesicles. Gel electrophoresis, circular dichroism spectroscopy and fluorescence methods were used to characterize the structure and the proton transport function of protein. UCP2 showed unique stable tetrameric forms in lipid bilayers. MD simulations using membrane lipids and principal component analysis support the experimental results and provided new molecular insights into the nature of noncovalent interactions in oligomeric UCP2. MD simulations indicate that UCP2 tetramers are asymmetric dimers of dimers, in which the interactions between the monomers forming the dimer are stronger than the interactions between the dimers within the tetramer. It is also shown that UCP2 has a specific tendency to form functional tetramers in lipid bilayers, capable of proton transport. The asymmetric nature of the UCP2 tetramer could act as a scaffold for regulating the activity of the monomeric units through cooperative intercommunication between these subunits. Under similar experimental conditions, the structurally comparable ADP/ATP carrier protein did not form tetramers in vesicles, implying that spontaneous tetramerization cannot be generalized to all MCF members.

STATEMENT OF SIGNIFICANCE

Self-assembly of membrane proteins plays a significant role in their biological function. In this article, both experimental and computational evidence are provided for spontaneous tetramerization of one of the mitochondrial uncoupling proteins (UCP2) in model lipid membranes. It is also shown that the tetrameric form of UCP2 is capable of proton transport, which leads to regulation of ATP synthesis in mitochondrion. Molecular dynamics simulations confirm the presence of asymmetric UCP2 tetramers as a potential scaffold for regulating the activity of the monomeric units through mutual intercommunication. The outcome of this study provides a solid ground for potential co-existence of monomeric and multimeric functional forms of UCPs that contributes to a deeper molecular insight into their structure and function.
West Nile virus-inclusive single-cell RNA sequencing reveals heterogeneity in the type I interferon response within single cells
Authors: O’Neal Justin T. , Upadhyay Amit A. , Wolabaugh Amber , Patel Nirav B. , Bosinger Steven E. , Suthar Mehul S.
Published: October 2018

West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus of global importance. Neuroinvasive WNV infection results in encephalitis and can lead to prolonged neurological impairment or death. Type I interferon (IFN-I) is crucial for promoting antiviral defenses through the induction of antiviral effectors, which function to restrict viral replication and spread. However, our understanding of the antiviral response to WNV infection is mostly derived from analysis of bulk cell populations. It is becoming increasingly apparent that substantial heterogeneity in cellular processes exists among individual cells, even within a seemingly homogenous cell population. Here, we present WNV-inclusive single-cell RNA sequencing (scRNA-seq), an approach to examine the transcriptional variation and viral RNA burden across single cells. We observed that only a few cells within the bulk population displayed robust transcription of IFN-β mRNA, and this did not appear to depend on viral RNA abundance within the same cell. Furthermore, we observed considerable transcriptional heterogeneity in the IFN-I response, with genes displaying high unimodal and bimodal expression patterns. Broadly, IFN-stimulated genes negatively correlated with viral RNA abundance, corresponding with a precipitous decline in expression in cells with high viral RNA levels. Altogether, we demonstrated the feasibility and utility of WNV-inclusive scRNA-seq as a high-throughput technique for single-cell transcriptomics and WNV RNA detection. This approach can be implemented in other models to provide insights into the cellular features of protective immunity and identify novel therapeutic targets.

IMPORTANCE

West Nile virus (WNV) is a clinically relevant pathogen responsible for recurrent epidemics of neuroinvasive disease. Type I interferon is essential for promoting an antiviral response against WNV infection; however, it is unclear how heterogeneity in the antiviral response at the single-cell level impacts viral control. Specifically, conventional approaches lack the ability to distinguish differences across cells with varying viral abundance. The significance of our research is to demonstrate a new technique for studying WNV infection at the single-cell level. We discovered extensive variation in antiviral gene expression and viral abundance across cells. This protocol can be applied to primary cells orin vivomodels to better understand the underlying cellular heterogeneity following WNV infection for the development of targeted therapeutic strategies.
Prevention of EloR/KhpA heterodimerization by introduction of site-specific amino acid substitutions renders the essential elongasome protein PBP2b redundant in Streptococcus pneumoniae
Authors: Ruud Winther Anja , Kjos Morten , Stamsås Gro Anita , Håvarstein Leiv Sigve , Straume Daniel
Published: October 2018

The RNA binding proteins EloR and KhpA are important components of the regulatory network that controls and coordinates cell elongation and division in S. pneumoniae. Loss of either protein reduce cell length, and makes the essential elongasome proteins PBP2b and RodA dispensable. It has been shown previously in formaldehyde crosslinking experiments that EloR co-precipitates with KhpA, indicating that they form a complex in vivo. In the present study, we used 3D modeling and site directed mutagenesis in combination with protein crosslinking to further study the relationship between EloR and KhpA. Protein-protein interaction studies demonstrated that KhpA forms homodimers and that KhpA in addition binds strongly to the KH-II domain of EloR. Site directed mutagenesis identified isoleucine 61 (I61) as crucial for KhpA homodimerization. When substituting I61 with phenylalanine, KhpA lost the ability to homodimerize, while it still interacted strongly with EloR. In contrast, both homo- and heterodimerization were lost when I61 was substituted with tyrosine. By expressing these KhpA versions in S. pneumoniae, we were able to show that disruption of EloR/KhpA heterodimerization makes the elongasome redundant in S. pneumoniae. Of note, loss of KhpA homodimerization did not give rise to this phenotype, demonstrating that the EloR/KhpA complex is crucial for regulating the activity of the elongasome. In support of this conclusion, we found that localization of KhpA to the pneumococcal mid-cell region depends on its interaction with EloR. Furthermore, we found that the EloR/KhpA complex co-localizes with FtsZ throughout the cell cycle.

Importance

To ensure correct cell division, bacteria need to monitor the progression of cell division and coordinate the activities of cell division proteins accordingly. Understanding the molecular mechanisms behind these regulatory systems is of high academic interest and might facilitate the development of new therapeutics and strategies to combat pathogens. EloR and KhpA form a heterodimer that is part of a signaling pathway controlling cell elongation in the human pathogen S. pneumoniae. Here we have identified amino acids that are crucial for EloR/KhpA heterodimerization, and demonstrated that disruption of the EloR/KhpA interaction renders the cells independent of a functional elongasome. Furthermore, we found the EloR/KhpA complex to co-localize with the division ring (FtsZ) during cell division.