bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospecting Peptides Isolated From Black Soldier Fly (Diptera: Stratiomyidae) With Antimicrobial Activity Against Helicobacter pylori (Campylobacterales: Helicobacteraceae)
Authors: Alvarez Daniela , Wilkinson Kevin A , Treilhou Michel , Téné Nathan , Castillo Denis , Sauvain Michel
Published: November 2019

Helicobacter pylori (Marshall & Goodwin) is a widespread human pathogen that is acquiring resistance to the antibiotics used to treat it. This increasing resistance necessitates a continued search for new antibiotics. An antibiotic source that shows promise is animals whose immune systems must adapt to living in bacteria-laden conditions by producing antibacterial peptides or small molecules. Among these animals is the black soldier fly (BSF; Hermetia illucens Linnaeus), a Diptera that colonizes decomposing organic matter. In order to find anti-H. pylori peptides in BSF, larvae were challenged with Escherichia coli (Enterobacteriales: Enterobacteriaceae). Small peptides were extracted from hemolymph and purified using solid-phase extraction, molecular weight cutoff filtration and two rounds of preparative high performance liquid chromatography (HPLC). The anti-H. pylori fraction was followed through the purification process using the inhibition zone assay in brain-heart infusion agar, while peptides from uninoculated larvae had no activity. The inhibition halo of the active sample was comparable to the action of metronidazole in the inhibition zone assay. The purified sample contained four peptides with average masses of approximately 4.2 kDa that eluted together when analyzed by HPLC-mass spectrometry. The peptides likely have similar sequences, activity, and properties. Therefore, BSF produces inducible antibacterial peptides that have in vitro activity against H. pylori, which highlights BSF’s position as an important target for further bioprospecting.
First Records of Established Populations of Ixodes scapularis (Acari: Ixodidae) Collected From Three Nebraska Counties
Authors: Nielsen Lindsey E , Cortinas Roberto , Fey Paul D , Iwen Peter C , Nielsen David H
Published: November 2019

Reported cases of Lyme disease in Nebraska have been assumed to be imported from other endemic areas. Previous surveillance efforts provided no evidence of established populations as only individual specimens of Ixodes scapularis (Say) had been collected. In the winter of 2018, adult I. scapularis were found on a dog at Two Rivers State Recreation Area, Douglas County, prompting tick collection at the site and nearby natural areas. In May 2019, all life stages of host-seeking I. scapularis were collected using dragging and flagging techniques in sites located near the Platte River in Douglas, Sarpy, and Saunders counties. This is the first documentation of established populations of I. scapularis in Nebraska.
Immunotropic effects in cultured human blood mononuclear cells exposed to a 900 MHz pulse-modulated microwave field
Authors: Szymański Łukasz , Sobiczewska Elżbieta , Cios Aleksandra , Szymanski Pawel , Ciepielak Martyna , Stankiewicz Wanda
Published: November 2019

The specific biological effect of electromagnetic field (EMF) remains unknown even though devices present in our daily lives, such as smartphones and Wi-Fi antennae increase the environmental level of electromagnetic radiation. It is said that the human immune system is able to react to discrete environmental stimuli like EMF. To investigate the effect of 900 MHz microwave stimulation on the immune system our research aimed to analyze lymphocyte proliferation and observe and assess the basic immunoregulatory activities using a newly developed and improved anechoic chamber. Samples of mononuclear cells (PBMC) isolated from the blood of healthy donors were exposed to 900 MHz pulse-modulated radiofrequency radiation (20 V/m, SAR 0.024 W/kg) twice (15 min each) or left without irradiation (control group). Subsequently, the control and exposed cells were set up to determine several parameters characterizing T cell immunocompetence and monocyte immunogenic activity. Although the microcultures of PBMC exposed to radiofrequency radiation demonstrated higher immunogenic activity of monocytes (LM index) and T-cell response to concanavalin A than control cultures after first exposure, this parameter decreased after a second stimulation. Saturation of the interleukin-2 (IL-2) receptor rose significantly after the second day of exposure. On the other hand, response to mitogen dropped after EMF stimulation. The results suggest that PBMC are able to overcome stress caused by mitogens after stimulation with 900 MHz radiation.
When size does not matter: a rare case of popliteal artery aneurysm presenting with foot drop and its endovascular management
Authors: Yahng Jeong-moh J , Ying Lei
Published: November 2019

Popliteal artery aneurysms (PAA) are the commonest arterial aneurysm of the periphery. It is defined as focal dilation more than 50% of the normal vessel diameter, which usually varies between 7 and 11 mm. The most common presentation for PAA is claudication due to luminal stenosis caused by mural thrombus or acute limb ischaemia due to thromboembolism. It is much less common for patients to present with mass effect symptoms due to compression of adjacent structures, and of these, common peroneal nerve compression is particularly uncommon. We present a rare case of a 92-year-old female presenting with 4-month history of left foot drop with radiological evidence of common peroneal nerve compression secondary to PAA measuring 22 × 21 mm in size. To the best of our knowledge, this is the smallest reported popliteal aneurysm presenting with foot drop. We also present the endovascular treatment option used.
Overview of Exposure Therapy
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Exposure therapy is an extremely powerful technique for reducing pathological anxiety. As demonstrated in this chapter, this very common-sense strategy can be adapted to address a wide range of anxiety-based disorders. Although the efficacy of exposure has been long recognized, researchers and clinicians continue to find new ways to adapt exposure to more effectively address anxiety and barriers to treatment. This chapter reviews the use of in vivo, imaginal, and interoceptive exposure using brief case studies involving, posttraumatic stress disorder, obsessive-compulsive disorder, general anxiety disorder, and panic disorder. The chapter also discusses the increasing use of virtual reality exposure therapy.
How Well Does Exposure Therapy Work for Eating Disorders?
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

This chapter provides an overview of the current evidence supporting the use of exposure therapy for eating disorders. Although further research is needed (because the existing research base is relatively small compared to large exposure literature for anxiety disorders), exposure is an effective approach for addressing key transdiagnostic features in eating disorders, including eating-related fear and avoidance, body image anxiety, compulsive body checking and avoidance, and binge-eating and purging behaviors. Results are drawn from a range of study types, from single case studies to large, methodically rigorous controlled trials. Importantly, several of the studies reviewed in this chapter showed that exposure was helpful for patients who had been previously unable to derive benefit from viable alternative treatments. Thus, exposure may offer a critical “missing element” in treatment protocols that have a reasonably strong evidence base and yet leave room for improvement in outcomes.
Explaining Exposure Therapy to Your Patients
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Providing a rationale for exposure therapy to patients is a key element to successful exposure, especially when it has not been used previously or has been used inadequately. Patients who do not understand what is involved with exposure therapy are less likely to commit to what can seem like a scary departure from their normal patterns of avoidance and safety behaviors. Unless there is a clear reason not to do so, clinicians need to explain exposure to eating and food at the beginning of therapy and be prepared to come back to it later in treatment when using exposure for other targets (e.g., emotions, body image). The explanation itself can include direct education, analogies, historical review, and comparison with other disorders. Even psychoeducation itself can have an exposure element.
Exposure to Food and Eating
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Patients with eating disorders experience substantial fear of food and eating. Clinicians can use exposure to address the anxiety that underpins that fear. Specific foods are addressed, based on the nature of the fear associated with them. Sometimes patients avoid foods to reduce the fear that they will binge on them, while in other cases those foods are avoided due to the fear that eating them will result in uncontrollable weight gain. Weight status makes a difference here. Extremely low weight patients may need to gain weight before starting exposure, while other low weight patients can use exposure to help them gain weight. Non-underweight patients can use exposure to learn that their weight is not affected as they fear. Fears of specific foods or classes of food can be addressed using exposure, and this is a particularly useful approach when working with some manifestations of avoidant/restrictive food intake disorder.
When to Use Cognitive Therapy Techniques to Enhance the Effects of Exposure
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Given that one of the main objectives of exposure therapy is to alter individuals’ cognitions related to feared stimuli, cognitive therapy can be effectively used as an adjunctive strategy to exposure. However, it is important to note that behavioral change methods show greater effectiveness in reducing eating disorder symptoms as compared to cognitive therapy. There are also circumstances in which utilizing cognitive therapy as an adjunct to exposure is not warranted. Accordingly, clinicians need to use careful consideration when deciding whether to engage eating disorder patients in cognitive therapy. As a general rule of thumb, clinicians are encouraged to employ cognitive therapy techniques when a patient is demonstrating significant hesitancy to begin exposure or is deriving notably suboptimal benefit from exposure.
Practical Tips on Integrating Palliative Care
Authors: Sutton Brett , Marston Joan
Published: November 2019

Palliative care has, historically, largely been absent or deprioritized in humanitarian emergencies. There is now increasing recognition of the need for it to be an integral part of any humanitarian response and, equally, for its integration to be routine across the many dimensions of a response. Such integration requires an understanding of the core principles and practice of humanitarian responses, and the structures of local, regional, and international agencies and their teams. The Sphere standards, now incorporating palliative care, comprise the fundamental standards and guidelines for humanitarian responses; they should provide key guidance for palliative care practitioners and organizations. Equally, the cluster system provides a structure for coordination of all the sectors in emergencies, and palliative care must be provided within this structure when it is in place for humanitarian events, whether acute or protracted. One core principle that humanitarian action increasingly incorporates is that of localization, whereby the response must recognize and respect local leadership and decision-making. This is equally true with emergency medical teams (EMTs), even when deploying internationally, because local responses have been overwhelmed. Finally, integration must incorporate all components of a robust palliative care response, including policy and guidance; community, primary, and specialist practitioners; training and mentorship; equipment, medication, and infrastructure appropriate for palliative care; and a referral system that uses both local and national structures.
Noncommunicable Diseases in Crisis Regions
Authors: Sankaran Sujatha , Shamasunder Sriram , Glass Marcia , Leng Mhoira E.F.
Published: November 2019

Noncommunicable diseases (NCDs) include a broad umbrella of illnesses that do not have an infectious etiology and usually need a chronic disease approach. Much of the challenge behind caring for patients with NCDs in resource-limited settings is the paradigm shift that many patients require from receiving medical care for acute illnesses to managing chronic illnesses. A few common NCDs are reviewed here—cardiomyopathies, dementia, cirrhosis, malignancies, and kidney disease. The etiologies and symptomatic management of each of these conditions in crisis regions are reviewed.
Lake Charles: 1908–1926
Authors: Miller Craig A.
Published: November 2019

A brief history of DeBakey’s birthplace, Lake Charles, Louisiana, is provided. Michael observes and absorbs defining characteristics of his father: work ethic, self-discipline, precise thinking. He also appreciates and internalizes the qualities of his mother: kindness, charity, love. He has the typical boyhood friendships and mischief of the time and place, peppered with hints of genius. The family embarks on a six-month journey to Europe and the Middle East in Michael’s 13th year, which will shape and inform the young man’s perceptions of human society for the rest of his life. As an adolescent Michael decides to become a physician. He matriculates at Tulane University.
Houston: 1951–1956
Authors: Miller Craig A.
Published: November 2019

As the 1950s begin, DeBakey focuses his efforts on the new field of vascular surgery, and he recruits a stellar cast of surgeons for his faculty at Baylor, including Denton Cooley. New operations are devised to address aortic aneurysms and carotid disease. At home, Diana copes with her husband’s absences with stoic grace, and the four sons born to the DeBakeys also follow their father’s single-minded commitment to medicine. DeBakey participates in the Hoover Commission. By the mid-1950s, Baylor, in Texas, is a leading center in the world for vascular surgery. Plastic arterial grafts are invented.
Puzzles of Mental Illness
Authors: Horwitz Allan V.
Published: November 2019

This chapter considers the extensive array of answers various groups have provided to questions about the nature of mental illness and its boundaries with sanity. While all societies recognize a class of behaviors they call “madness,” they vary considerably in the content of this category and how it differs from normality. What distinguishes mental illnesses from other sorts of devalued conditions? Should medical, religious, psychological, legal, or no authority at all respond to the mentally ill? Why do some people become mad? What treatments might help them recover? The various responses that diverse societies have provided to these issues are both widely divergent and surprisingly similar to current understandings.
Epidural Hematoma
Authors: Kaoutzani Lydia , Stippler Martina
Published: November 2019

Although epidural hematomas (EDH) are not frequently seen with intracranial injury in trauma, they present an emergency situation that can result in significant mortality if not diagnosed and treated in a timely manner. EDH stems from bleeding from the bone rupturing an interosseous artery, the bone itself, or from a venous sinus laceration. Most EDH present with a classic biconvex shape on CT images. Venous EDH can cross the midline and are often found under the transverse or sagittal sinus. The current school of thought is that patients who present with a small (<10 mm maximal thickness) EDH with no neurological symptoms can be treated conservatively. Patients neurologically intact with a normal Glasgow Coma Scale score but an EDH of greater than 30 cc should undergo surgery.
Overview
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter provides an overview of the scope of the book. It also provides guidance for clinical medical students studying ear, nose, and throat (ENT). A detailed curriculum and a set of learning objectives are provided. The role of research and audit in ENT practice is highlighted.
The middle ear
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

The structure and function of the ear are documented, along with congenital abnormalities. The function of the Eustachian tube and symptoms caused by a blocked or patulous tube are discussed, along with possible treatments. Acute otitis media and its complications and management are explored. Strategies for managing glue ear and chronic suppurative otitis media with and without cholesteatoma are investigated. Surgical intervention is highlighted. The condition of otosclerosis and its diagnosis and management options are listed.
The nose and sinuses
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter describes the anatomy and function and lists the common conditions affecting the nose. The investigation, diagnosis, and medical and surgical management of rhinosinusitis with or without polyps are discussed. Complications of sinusitis are outlined, along with their modes of presentation. Common septal problems and granulomatous conditions, as well as rare malignancies, are listed.
The mouth, tonsils, and adenoids
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

The anatomy of the oral cavity is illustrated. Oral conditions from ulcers to white patches are described, in conjunction with their management plans. This includes treatment and staging of oral malignancies. The management of tonsillitis and adenoidal conditions, including glandular fever, is outlined. Indications for tonsillectomy are discussed. The presentation, investigation, staging, and treatment of tonsillar cancer are documented.
The salivary glands
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter describes the anatomy, function, and investigation of the salivary glands, including conditions affecting the parotid, submandibular, and sublingual salivary glands. Benign and malignant conditions of the glands are described, including surgical intervention.
The thyroid
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter describes the embryology and anatomy of the thyroid gland. Investigation and treatment of thyroid disorders, including neoplastic conditions, are outlined. Multiple endocrine neoplasia (MEN) syndromes and their features are tabulated. Risks and complications of thyroid surgery are discussed.
ENT manifestations of AIDS
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter provides an overview of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and its relationship to ear, nose, and throat (ENT) problems. The pathology, effects, diagnosis, and treatment of the condition are outlined. The specific anatomically classified ENT conditions are described, along with their investigation.
Introduction
Authors: Barreveld Antje M. , Hogans Beth B.
Published: November 2019

Pain has profound effects on human productivity and quality of life. Pain can result in patients experiencing stigma in addition to the profound suffering intrinsic to pain. Since the early 70s, much has been learned about pain through research and collaboration of diverse healthcare professionals and scientists. Despite advances in understanding pain causes, processes, and potential treatments, progress in the preparation of healthcare professionals has been slow. This book represents a collaborative effort of a wide variety of experts in pain, including physicians, nurses, clinical psychologists, pharmacists, scientists, physical therapists and others. The content is organized around learning objectives and targets of the needs of early career health practitioners, including physicians, nurse practitioners, physician assistants, and others. While this book may serve as a refresher, many will be learning this material for the first time. We hope to inspire our readers to engage in meaningful therapeutic partnerships with their patients utilizing the broadest range of effective pain management approaches and therapies with an awareness of safety, pain relief, and the highly individualized nature of pain. Attaining competence in pain care essentials is immensely rewarding for patients, caregivers, and healthcare providers alike.
Pain Appraisal
Authors: Abrecht Chris R. , Hogans Beth B. , Barreveld Antje M.
Published: November 2019

Chapter 4 describes the terminology and assessment of pain and addresses the need for a fundamental “language of pain.” Because pain is so prevalent and because clinical decision-making in acute care settings relies heavily on rapid and reliable pain appraisal, it is essential to understand the properties of commonly used tools for assessing pain and evaluating responses to pain treatments. The tools appropriate for pain assessment vary across the life span, and administration of age-appropriate instruments for pain assessment is a foundational clinical skill in pain care. The historical origins of pain appraisal are discussed with relevance to current practice. This chapter also introduces the concept of the basic classification of pain according mechanism class: specifically, pain as nociceptive, neuropathic, and inflammatory. Additional pain terminology is introduced, such as the terms hyperalgesia and allodynia; excerpted terms from the formal International Association for the Study of Pain taxonomy are referenced.
Radiotherapy-induced heart disease: a review of the literature
Authors: Zou Bingwen , Schuster Julius Philipp , Niu Kerun , Huang Qianyi , Rühle Alexander , Huber Peter Ernst
Published: November 2019

Radiotherapy as one of the four pillars of cancer therapy plays a critical role in the multimodal treatment of thoracic cancers. Due to significant improvements in overall cancer survival, radiotherapy-induced heart disease (RIHD) has become an increasingly recognized adverse reaction which contributes to major radiation-associated toxicities including non-malignant death. This is especially relevant for patients suffering from diseases with excellent prognosis such as breast cancer or Hodgkin’s lymphoma, since RIHD may occur decades after radiotherapy. Preclinical studies have enriched our knowledge of many potential mechanisms by which thoracic radiotherapy induces heart injury. Epidemiological findings in humans reveal that irradiation might increase the risk of cardiac disease at even lower doses than previously assumed. Recent preclinical studies have identified non-invasive methods for evaluation of RIHD. Furthermore, potential options preventing or at least attenuating RIHD have been developed. Ongoing research may enrich our limited knowledge about biological mechanisms of RIHD, identify non-invasive early detection biomarkers and investigate potential treatment options that might attenuate or prevent these unwanted side effects. Here, we present a comprehensive review about the published literature regarding clinical manifestation and pathological alterations in RIHD. Biological mechanisms and treatment options are outlined, and challenges in RIHD treatment are summarized.
Autoinflammatory disease with corneal and mucosal dyskeratosis caused by a novel NLRP1 variant
Authors: Herlin Troels , Jørgensen Sofie E , Høst Christian , Mitchell Patrick S , Christensen Maria Hønholt , Laustsen Mira , Larsen Dorthe A , Schmidt Florian I , Christiansen Mette , Mogensen Trine H
Published: November 2019

Objectives

Here we investigated a patient with inflammatory corneal intraepithelial dyskeratosis, mucosal inflammation, tooth abnormalities and, eczema to uncover the genetic and immunological basis of the disease.

Methods

On suspicion of an autoinflammatory condition, Sanger sequencing of nucleotide-binding oligomerization domain-like, leucine-rich repeat pyrin domain containing 1 (NLRP1) was performed and combined with an in vitro inflammasome reconstitution assay to measure caspase-1-mediated IL-1β cleavage, stimulation of patient peripheral blood mononuclear cells (PBMCs) and whole blood to measure IL-1β, IL-18 production and quantification of apoptosis-associated speck-like protein containing CARD (ASC) speck formation as a measure of inflammasome activation by flow cytometry.

Results

Sanger sequencing revealed a novel mutation (c.175G>C, p.A59P; NM_33004.4) in the inflammasome molecule NLRP1 segregating with disease, although with incomplete penetrance, in three generations. We found that patient PBMCs produced increased IL-1β in response to inflammatory stimuli, as well as increased constitutive levels of IL-18. Moreover, we demonstrate that expression of the identified NLRP1 A59P variant caused spontaneous IL-1β cleavage to mature IL-1β. In addition, patient PBMCs responded to NLRP1 stimulation with increased ASC speck formation as a reflection of elevated inflammasome activity.

Conclusion

We demonstrate that this novel NLRP1 A59P variant caused increased activation of the NLRP1 inflammasome, resulting in constitutively and inducibly elevated IL-1β and IL-18 synthesis. We suggest the NLRP1 mutation underlies the pathogenesis of this rare autoinflammatory dyskeratotic disease inherited in an autosomal dominant manner with incomplete penetrance in the patient and within the family for several generations.
Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus
Authors: Jang Se Gwang , Lee Jaeseon , Hong Seung-Min , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan
Published: November 2019

Objectives

Mesenchymal stem cells (MSCs) are considered potential therapeutic agents for treating autoimmune disease because of their immunomodulatory capacities and anti-inflammatory effects. However, several studies have shown that there is no consistency in the effectiveness of the MSCs to treat autoimmune disease, including SLE. In this study, we investigated whether metformin could enhance the immunoregulatory function of MSCs, what mechanism is relevant, and whether metformin-treated MSCs could be effective in an animal lupus model.

Methods

Adipose-derived (Ad)-MSCs were cultured for 72 h in the presence of metformin. Immunoregulatory factors expression was analysed by real-time PCR and ELISA. MRL/lpr mice weekly injected intravenously with 1 × 106 Ad-MSCs or metformin-treated Ad-MSCs for 8 weeks. 16-week-old mice were sacrificed and proteinuria, anti-dsDNA IgG antibody, glomerulonephritis, immune complex, cellular subset were analysed in each group.

Results

Metformin enhanced the immunomodulatory functions of Ad-MSCs including IDO, IL-10 and TGF-β. Metformin upregulated the expression of p-AMPK, p-STAT1 and inhibited the expression of p-STAT3, p-mTOR in Ad-MSCs. STAT1 inhibition by siRNA strongly diminished IDO, IL-10, TGF-β in metformin-treated Ad-MSCs. As a result, metformin promoted the immunoregulatory effect of Ad-MSCs by enhancing STAT1 expression, which was dependent on the AMPK/mTOR pathway. Administration of metformin-treated Ad-MSCs resulted in significant disease activity improvement including inflammatory phenotype, glomerulonephritis, proteinuria and anti-dsDNA IgG antibody production in MRL/lpr mice. Moreover, metformin-treated Ad-MSCs inhibited CD4-CD8- T-cell expansion and Th17/Treg cell ratio.

Conclusion

Metformin optimized the immunoregulatory properties of Ad-MSCs and may be a novel therapeutic agent for the treatment of lupus.
Institution-driven innovation in Guangdong firms: Moderating effects of in-house formal R&D and industrial environment turbulence
Authors: Tang Yongli , Hu Xinyue , Petti Claudio , Thürer Matthias
Published: November 2019

This article explores the moderating effects of in-house formal R&D and industrial environment turbulence on the relationship between institutional drivers, in terms of incentives and pressures, and firm innovation. Hypotheses were tested on a sample of manufacturing firms in Guangdong Province of China, where institutional changes and governmental policies play prominent roles in shaping innovation. Results show a positive main effect of institutional incentives, but an insignificant main effect of institutional pressures. In-house formal R&D and industrial turbulence negatively moderate the institutional incentives–innovations relationship, yet positively moderate the institutional pressures–innovations relationship. This study links the innovation systems literature with the institution-based view and deepens the understanding of the joint forces of institutional transitions, industrial changes, and resource heterogeneity in shaping innovation. The findings also inform managers and policymakers in institutional transition environments to better manage institutional drivers of innovation by considering firm- and industry-specific characteristics.
A moveable feast—economic substance and holding entities
Authors: Fife Ashley
Published: November 2019

The economic substance requirements that the European Union insisted that a number of international financial centres introduce may be the most complex and far-reaching of international initiatives to impact on those jurisdictions in recent years. The requirements extend beyond due diligence, reporting and exchange of information to potentially impact on the way in which entities resource and carry on business in or from those jurisdictions. However, not all sectors of international business are impacted in the same way or to the same extent. This article considers certain aspects of the economic substance requirements relevant to private client structures, with a particular focus on the impact on holding entities. The treatment of holding entities under economic substance legislation in a number of C.2.2 jurisdictions may not be settled and this article explores how it may evolve.
Keeping time in the lamina terminalis: Novel oscillator properties of forebrain sensory circumventricular organs
Authors: Northeast Rebecca C. , Chrobok Lukasz , Hughes Alun T. L. , Petit Cheryl , Piggins Hugh D.
Published: November 2019

Drinking behavior and osmotic regulatory mechanisms exhibit clear daily variation which is necessary for achieving the homeostatic osmolality. In mammals, the master clock in the brain's suprachiasmatic nuclei has long been held as the main driver of circadian (24 h) rhythms in physiology and behavior. However, rhythmic clock gene expression in other brain sites raises the possibility of local circadian control of neural activity and function. The subfornical organ (SFO) and the organum vasculosum laminae terminalis (OVLT) are two sensory circumventricular organs (sCVOs) that play key roles in the central control of thirst and water homeostasis, but the extent to which they are subject to intrinsic circadian control remains undefined. Using a combination of ex vivo bioluminescence and in vivo gene expression, we report for the first time that the SFO contains an unexpectedly robust autonomous clock with unusual spatiotemporal characteristics in core and noncore clock gene expression. Furthermore, putative single‐cell oscillators in the SFO and OVLT are strongly rhythmic and require action potential‐dependent communication to maintain synchrony. Our results reveal that these thirst‐controlling sCVOs possess intrinsic circadian timekeeping properties and raise the possibility that these contribute to daily regulation of drinking behavior.
Zebrafish prmt7 negatively regulates antiviral responses by suppressing the retinoic acid‐inducible gene‐I‐like receptor signaling
Authors: Zhu Junji , Liu Xing , Cai Xiaolian , Ouyang Gang , Fan Sijia , Wang Jing , Xiao Wuhan
Published: November 2019

Arginine methylation is a post‐translational modification in histone and nonhistone proteins that can affect numerous cellular activities. Protein arginine methyltransferase 7 (Prmt7), a type III arginine methyltransferase, catalyzes the formation of stable monomethylarginines of histones. The role of PRMT7 in virus‐induced innate immunity signaling, however, remains largely unknown. We demonstrate that zebrafish prmt7 could be inhibited by spring viremia of carp virus (SVCV) and grass carp reovirus (GCRV) infection. The overexpression of prmt7 suppresses cellular antiviral responses that are partially dependent on the arginine methyltransferase activity of prmt7. Consistently, prmt7‐null zebrafish were more resistant to SVCV or GCRV infection, exhibiting enhanced expression of key antiviral genes and fewer necrotic cells in the liver and kidney upon viral infection. Furthermore, we established a zebrafish model to investigate grass carp hemorrhagic disease. Our findings suggest that by suppressing the RIG‐I‐like receptors signaling, zebrafish prmt7 negatively regulates antiviral responses, indicating the vital role of prmt7 and its arginine methyltransferase activity in innate immunity.
Update on exhaled breath condensate analyses in occupational disease
Authors: Maestrelli Piero , Mason Paola , Guarnieri Gabriella
Published: November 2019

Purpose of review

The present work represents an update of the review published in this journal by Corradi et al., regarding the use of exhaled breath condensate (EBC) to investigate occupational lung diseases.

Recent findings

The relevant literature was searched in the Medline database, assessed through PubMed using key terms such as ‘breath AND condensate AND occupational’. Eleven pertinent publications were retrieved between January 2018 and October 2019. One article only was related to occupational allergy, and the conclusion is that EBC hydrogen peroxide is not an useful marker in laboratory animal allergy. The biomarkers of exposure most often assessed with EBC are metals. However, it is controversial whether this approach has any advantage over the conventional environmental monitoring. The biomarkers of effect studied by the majority of investigations were those related to oxidative stress. They appear consistently elevated upon occupational exposures to various agents, including welding fumes, crystalline silica, nanomaterials and chemicals.

Although EBC represent a suitable tool to sample airway lining fluid in a noninvasive manner, it remains a niche approach to the investigation of occupational diseases. The confounding influence of EBC dilution should be better addressed in the expression of the results.
Postless Hip Traction Table for Combined Femoral and Pelvic Fractures
Authors: Aprato Alessandro , Parisi Gennaro , D’Amelio Andrea , Massè Alessandro
Published: November 2019

In multiple injured patients, the association of femoral and pelvic fractures is not uncommon. Femoral reduction and fixation in those patients may be performed with a traction table and a perineal post, but it may result in various groin-related complications, including the displacement of the pubic rami, pudendal nerve neurapraxias, vaginal tears, and scrotal necrosis. The aim of this study was to describe a technique for femur fracture distraction without the use of a perineal post in patients with pelvic trauma. Here, we describe the technical details and 5 cases of femoral fracture associated with pelvic fractures treated with a postless distraction technique. Our preliminary results using this technique show a sufficient distraction to allow reduction and internal fixation of the femoral fracture with a standard femoral nail.
Internally Fabricated Chimera Anterolateral Thigh-Amputate Flaps for Metachronous Reconstruction
Authors: Osinga Rik , Lo Steven John
Published: November 2019

Background:

The chimera flap is a versatile and exciting tissue composition for the reconstruction of complex tissue defects.

Methods:

Here, we present 2 cases of internally fabricated anterolateral thigh (ALT)-amputate chimera flaps for metachronous transfer.

Results:

A 22-year-old man (case 1) developed extended soft tissue necrosis in both legs following meningococcal septicemia. Before unilateral amputation, a fasciocutaneous flap based on the posterior tibial artery perforators was saved and ectopically implanted onto the ipsilateral thigh, creating an ALT-amputate chimera flap. Three months later, it was shown that the islanded ALT-amputate chimera flap remained well vascularized on either pedicle alone. Thus, a “true chimera circulation” over the scar between the 2 flaps must have developed. Subsequent free tissue transfer to the remaining right lower leg was performed successfully with uneventful healing. A 57-year-old fisherman (case 2) suffered a traumatic avulsion of his left thumb, which was ectopically replanted onto the contralateral thigh, creating an ALT-amputate chimera flap. After 3 months, the flap was raised and orthotopically replanted successfully with arthrodesis through the metacarpophalangeal joint. The previously coapted radial digital lateral femoral cutaneous nerve was coapted in the palm, and an flexor digitorum superficialis (FDS) ring transfer was performed for flexor pollicis longus (FPL) reconstruction.

Conclusions:

To the best of our knowledge, these are the first case reports using the descending branch of the lateral circumflex femoral artery system for (1) temporary ectopic implantation of a thumb and (2) temporary implantation of fasciocutaneous tissue based on posterior tibial artery perforators just before below knee amputation to reconstruct the contralateral leg.
Prediction of Epithelial Ovarian Cancer Outcomes With Integration of Genomic Data
Authors: NEWTSON ANDREEA M. , DEVOR ERIC J. , GONZALEZ BOSQUET JESUS
Published: November 2019

Some of the patients with epithelial ovarian cancer will not respond to initial therapy. These patients have a poor prognosis. Our aim was to identify patients with a worse prognosis by integrating clinical, pathologic, and genomic data. Using publicly available genomic data and integrating it with clinical data, we significantly improved the prediction of patients with worse surgical outcomes and those who do not respond to initial chemotherapy. We further improved these models with more precise data collection and better understanding of the genetic background of the studied population. Better prediction will lead to better patient classification and opportunities for individualized treatment.
Prescribing Trends of Topical Glaucoma Medications in Australia From 2001 to 2017
Authors: Perera Nayomi , Pinnuck Brigid C. , Jamieson Michael P.H. , Ling Damien , Williams Michael , Chen Oliver
Published: November 2019

Precis:

As new glaucoma treatments arise, including minimally invasive glaucoma surgeries and new classes of glaucoma medications, it is important to examine the prescription trends of current topical glaucoma medications and how they may change.

Purpose:

To determine the prescribing trends of topical glaucoma medications in Australia from 2001 to 2017.

Methods and Analysis:

Pharmaceutical Benefits Scheme (PBS) item numbers were used to determine glaucoma medication prescribing rates from 2001 to 2017. All data were adjusted for population (/100,000) as per the Australian Bureau of Statistics (ABS) population data.

Results:

Overall prescription rates for glaucoma medications ranged between 67,904 and 86,936 per 100,000 from 2001 to 2017. An upward trend was noted from 2001 to 2015, with the exception of a notable decline in 2013 by 14.7%, before then increasing by 13.7% in 2014. After 2015, prescribing rates were seen to decrease over the subsequent years in the study period. Latanoprost remained the most prescribed medication and prostaglandin the most prescribed class. Prescribing rates of single-agent beta-blockers were noted to decrease during the 17-year period, particularly with the introduction of combination agents, which note an upward trend. Brinzolamide/brimonidine has increased by 50.0% from 2016 to 2017.

Conclusions:

Total rates of prescriptions have remained relatively stable from 2001 to 2017. The number of medications prescribed when considering combination agents separately was seen to be increasing from 2001 to 2015. From 2015 to 2017, a downward trend was noted in the number of medications prescribed. Prostaglandins remain the most prescribed class throughout the study period.
The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy
Authors: Yuksel Nilay , Yaman Derya , Tugce Pasaoglu Ozge , Pasaoglu Hatice
Published: November 2019

Purpose:

To evaluate the effects of cigarette smoking on oxidative stress (OS) and mitochondrial biogenesis related parameters in patients Graves Ophthalmopathy (GO).

Methods:

Patients with moderate-to-severe GO according to the European Group on Graves Orbitopathy (EUGOGO) criteria were prospectively enrolled in this study. Age- and sex-matched healthy volunteers who applied to outpatient clinic due to refractive problems consisted the control group. Participants were divided into 4 groups based on their diagnosis and smoking status: group 1 (n = 30) smoker GO patients, group 2 (n = 30) nonsmoker GO patients, group 3 (n = 30) smoker healthy controls, and group 4 (n = 30) nonsmoker healthy controls. In the sera, total antioxidant status, total oxidant status and OS index values, peroxisome proliferator-activated receptor-γ coactivator 1-α, mitochondrial transcriptional factor A levels, and paraoxonase-1 enzyme activity were evaluated.

Results:

Total oxidant status and OS index values were the highest in group 1 compared to other groups (p= 0.031,p= 0.042; respectively). There was no statistically significant difference in total antioxidant status and peroxisome proliferator-activated receptor-γ coactivator 1α levels among the groups (p= 0.521,p= 0.388; respectively). Paraoxonase-1 enzyme activity was the lowest in group 1 and highest in group 4 (p= 0.024). The levels of mitochondrial transcriptional factor A was the lowest in group 1 compared to other groups (p= 0.012).

Conclusions:

Cigarette smoking in GO patients seems to be a risk factor that increases OS, and therefore, it may have an unfavorable impact on the mitochondrial biogenesis.
Development and Validation of a Questionnaire to Measure Psychosocial Work Stressors in Modern Working Environments
Authors: Diebig Mathias , Dragano Nico , Körner Ulrike , Lunau Thorsten , Wulf Ines Catharina , Angerer Peter
Published: November 2019

Objective:

The rapid development of technology is changing working conditions of many employees. With this, appropriate measurement instruments to capture work-related psychosocial risks to create healthy working conditions are becoming more and more important. Therefore, we developed and validated a questionnaire to assess stressors in work settings which are characterized by a high degree of digitization.

Method:

The validation was based on two independent studies with data collected in four subsamples. All participants were asked about their working conditions and health-related topics using online questionnaires.

Results:

The resulting 16-item questionnaire consists of five scales: work load, boundary permeability, participation, leader support, and usability.

Conclusions:

The results show that the five identified stressors showed acceptable to good values with regard to reliability (internal consistencies, test-retest reliabilities, and interrater agreement) as well as (convergent and concurrent) validity.
Incidental Effect of Long-Term Tacrolimus Treatment on Sporadic Vestibular Schwannoma Volume Shrinkage and Clinical Improvement
Authors: Delmas Justine , Varoquaux Arthur , Troude Lucas , Salburgo Florent , Lavieille Jean-Pierre , Montava Marion
Published: November 2019

Objective:

We describe the effect of long-term tacrolimus delivery on sporadic vestibular schwannoma (VS).

Patient:

A 48-year-old woman who was diagnosed a right VS.

Intervention:

Long-term tacrolimus delivery following liver transplant.

Main Outcome Measures:

Clinical examination, audiometric test, and gadolinium-contrasted magnetic resonance imaging.

Results:

During the reported follow-up period, the patient felt hearing improvement especially in noisy environment. This was consistent with a clear audiometric improvement. Over a 26 months follow-up period, we noticed a 50% volume regression and a 40% decrease in the intensity of enhancement of the tumor after gadolinium injection.

Conclusion:

Tacrolimus, an immunosuppressant used to prevent rejection in organ transplant, could lead to VS volume shrinkage and hearing improvement. Tacrolimus could be an interesting new therapeutic weapon, especially for VS in Neurofibromatosis type 2.
Effects of Age at Auditory Brainstem Implantation: Impact on Auditory Perception, Language Development, Speech Intelligibility
Authors: Aslan Filiz , Ozkan Hilal Burcu , Yücel Esra , Sennaroğlu Gonca , Bilginer Burçak , Sennaroğlu Levent
Published: November 2019

Objective:

To study the effect of age at auditory brainstem implant (ABI) surgery on auditory perception, language, and speech intelligibility.

Study Design:

Retrospective single cohort design.

Setting:

Tertiary referral center.

Patients:

In this study, 30 pediatric ABI users with no significant developmental issues were included. Participants were divided into two groups, according to age at surgery (Early Group: < 3 yr old [n = 15], Late Group: ≥ 3 yr old [n = 15]). Groups were matched by duration of ABI use and participants were evaluated after 5 years (±1 yr) experience with their device. The mean age at ABI surgery was 22.27 (ranged ± 6.5) months in the early group, 45.53 (ranged ± 7.9) months in the late group.

Intervention(s):

Retrosigmoid craniotomy and ABI placement.

Main Outcome Measure(s):

Auditory perception skills were evaluated using the Meaningful Auditory Integration Scale and Categories of Auditory Performance from the Children's Auditory Perception Test Battery. We used a closed-set pattern perception subtest, a closed-set word identification subtest, and an open-set sentence recognition subtest. Language performance was assessed with the Test of Early Language Development and Speech Intelligibility Rating, which was administered in a quiet room.

Results:

In this study, the results demonstrated that the Early Group's auditory perception performance was better than the Late Group after 5 years of ABI use, when children had no additional needs (U = 12, p < 0.001). Speech intelligibility was the most challenging skill to develop, in both groups. Due to multiple regression analysis, we found that auditory perception categories can be estimated with speech intelligibility scores, pattern perception scores, receptive language scores, and age at ABI surgery variables in ABI users with no additional handicaps.

Conclusions:

ABI is a viable option to provide auditory sensations for children with cochlear anomalies. ABI surgery under age 3 is associated with improved auditory perception and language development compared with older users.