bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Right Ventricular Failure
Authors: Hoyler Marguerite , Ivascu Natalia S.
Published: November 2020

This chapter examines postoperative right ventricular (RV) failure. RV failure is not uncommon following cardiac surgery and often portends a worse clinical outcome. After establishing the diagnosis of RV failure, the central goal of treatment is to increase RV function in order to achieve adequate left ventricular preload and cardiac output. Key management points include decreasing RV volume and preload, increasing RV contractility, reducing RV afterload, maintaining normal rate and rhythm, and supporting RV and systemic perfusion. Diuresis, inodilators and inopressors, and inhaled direct pulmonary vasodilators are mainstays of treatment. Meanwhile, serial transthoracic echocardiogram and central venous pressure measurements, as well as markers of cardiac output and systemic perfusion, are critical for guiding RV failure management.
Postoperative Ventricular Fibrillation
Authors: Singh Gurbinder , Ivascu Natalia S.
Published: November 2020

This chapter assesses ventricular arrhythmias. The most common ventricular arrhythmias are premature ventricular complexes (PVCs). Occasional PVCs are rarely harmful and may be related to tissue reperfusion or electrolyte abnormalities. Other types of ventricular arrhythmias are non-sustained ventricular tachycardia and ventricular tachyarrhythmias, which include ventricular tachycardia and ventricular fibrillation. Ventricular tachycardia is defined as a rate >100 bpm with 3 or more ventricular complexes in a row, which is sustained. Meanwhile, ventricular fibrillation is a form of complex ventricular arrhythmias and usually indicates a left ventricular problem. The possible causes of ventricular arrhythmias in the perioperative period include ischemia; electrolyte abnormalities such as hypokalemia, hyperkalemia, hypomagnesemia, and hypocalcemia; pulmonary artery catheters; hypothermia and metabolic acidosis; antiarrhythmic medications; adrenergic medications and inotropes; and pacing wires. The treatment of ventricular arrhythmias includes cardioversion and defibrillation; identification and treatment of ischemia, including coronary artery bypass grafting, valvular surgery, and aortic root surgery; and the administration of lidocaine and amiodarone.
Left Ventricular Assist Device Troubleshooting: Hypotension
Authors: Griffin Jan M. , Taha Bushra W. , Naka Yoshifumi
Published: November 2020

The differential diagnosis for postoperative hypotension after left ventricular assist device (LVAD) implantation is broad and is defined as a mean arterial pressure <60 mm Hg for continuous-flow LVADs. Etiologies to consider include vasodilatory shock from systemic inflammatory response syndrome or sepsis, hypovolemia, cardiogenic shock secondary to right ventricular dysfunction, cardiac tamponade, pulmonary embolus or tension pneumothorax, and device-related complications that obstruct flow through the pump. Clinical examination is an important component of the initial evaluation. Assessment of LVAD flows/cardiac output can help to differentiate between vasodilatory and non-vasodilatory shock. The cause of non-vasodilatory shock can be further narrowed with the aid of pulmonary artery catheter placement, transthoracic or transesophageal echocardiography, and chest radiography and guide specific treatments and interventions.
Gastrointestinal Bleeding in the Setting of Left Ventricular Assist Device Support
Authors: Kiyatkin Michael E. , Faye Adam S. , Gonda Tamas A.
Published: November 2020

In this chapter, the authors discuss the pathophysiology, diagnosis, and treatment of gastrointestinal bleeding (GIB) in the setting of left ventricular assist device (LVAD) support. Briefly, LVAD surgery has become widespread. Despite numerous advances, LVADs continue to be associated with a high incidence of GIB. The pathophysiology of this is multifactorial, with contributors including acquired von Willebrand disease and angiodysplasia. When GIB is suspected, it is imperative to consult a gastroenterologist and cardiologist. Endoscopy is the principal diagnostic and therapeutic modality. Occult GIB may be investigated with enteroscopy, capsule endoscopy, and angiography. Pharmacologic treatment may include a brief hold of anticoagulation and initiation of angiotensin-converting enzyme inhibitors, proton pump inhibitors, and octreotide, among other drugs. Evidence for pharmacotherapy, however, is limited. At the time of discharge, the focus should be on secondary prevention. In summary, LVAD-related GIB is a unique clinical problem that requires multimodal and multidisciplinary management.
Critical Concepts in Extracorporeal Life Support for Cardiogenic Shock
Authors: Diaz Soto Juan C. , Fried Justin A. , Reshad Garan A.
Published: November 2020

This chapter examines venoarterial extracorporeal membrane oxygenation (VA-ECMO), also known as extracorporeal life support, which is increasingly used to support patients with refractory cardiogenic shock and cardiopulmonary collapse. VA-ECMO is a simplified form of cardiopulmonary bypass which provides both circulatory support and gas exchange. The underlying etiology of the cardiogenic shock is critical to determine the optimal use of this therapy and prognosis. Primary ischemic etiologies such as acute myocardial infarction and non-ischemic etiologies such as fulminant myocarditis, peripartum cardiomyopathy, decompensated pulmonary hypertension, and primary graft failure following cardiac transplant causing cardiogenic shock are frequent indications for VA-ECMO and represent a heterogenous postoperative patient population. However, despite VA-ECMO's broad applicability, a number of contraindications exist: severe, irreversible, non-cardiac organ failure limiting survival; irreversible cardiac failure if transplantation or long-term ventricular assist device will not be considered; severe aortic insufficiency; and aortic dissection. Understanding the potential complications and the hemodynamic consequences of VA-ECMO support is critical to recognize and mitigate some of the risks associated with this therapy and to avoid some common pitfalls with its use. The chapter then looks at the management of patients on VA-ECMO.
Postoperative Pneumothorax
Authors: Doolan Aoife , Curley Gerard
Published: November 2020

This chapter reviews the management of a stable and tension pneumothorax after cardiac surgery and discusses persistent air leaks. It examines the features of pneumothorax on chest ultrasonography and compares the diagnostic accuracy of ultrasound to chest radiography and chest computed tomography (CT). It discusses the technique for needle decompression and chest drain insertion and troubleshoots problems with both. It describes the characteristics of persistent air leaks and summarizes the grading system. It compares the features of alveolar-pleural fistulas to bronchopleural fistulas and discusses various diagnostic techniques including chest CT, sequential balloon occlusion, and bronchoscopy. It outlines various treatment options including ventilation strategies, Heimlich valves, chemical pleurodesis, endobronchial/intrabronchial valves, occlusion coils, self-expanding airway stents, and surgery.
Postoperative Cerebrovascular Injury
Authors: Quigley Naomi , O’Leary Ruth-Aoibheann
Published: November 2020

This chapter studies perioperative stroke, which is defined as an ischemic or hemorrhagic infarction that occurs either during surgery or in the first 30 postoperative days. Risk factors for perioperative stroke can be categorized as patient- and procedure-related. Preoperative carotid endarterectomy should be considered particularly in patients with symptomatic disease or tight stenosis. Given the patient and procedural risk factors, there is a high index of suspicion for perioperative stroke. Timely computed tomography angiogram is key to diagnosis as it can overrule intraparenchymal hemorrhage and demonstrate large-vessel occlusion. Thrombectomy may be considered in the first 12 hours following symptom onset, especially in posterior circulation strokes. Meanwhile, anticoagulation in this setting requires multidisciplinary input due to the risk of hemorrhagic transformation but is likely safe 14 days post-stroke.
Introduction
Authors: Miller Michael M. , Peppin John F.
Published: November 2020

At the same time that it became apparent that overdose toxicity and adverse effects limited the utility of barbiturates to treat anxiety and insomnia, a new class of drugs emerged in the 1950s and 1960s: benzodiazepines. With a rapid onset of action, these new drugs were highly effective in reducing anxiety and promoting sleep when used short term. Rapidly becoming some of the most prescribed drugs in the world, benzodiazepines brought with them a Pandora’s box of potential risks that weren’t at first fully appreciated. Although rarely fatal when taken alone, benzodiazepines have been shown to be correlated with polydrug overdose mortality. With prolonged exposure these drugs can lead to tolerance, physical dependence, and addiction. They can also launch a vicious cycle of rebound after initially relieving anxiety, they can lead to a state of tolerance with the need for increasing doses to achieve the same effect, resulting in more subjectively experienced anxiety. Rebound insomnia is a well-known feature of the long-term use of these agents. Despite these risks, these drugs were extremely popular upon their introduction into the medical marketplace and they became among the most frequently prescribed pharmaceuticals in America, with a variety of agents in this class of drugs being introduced. There then emerged the so-called Z-drugs (e.g., zolpidem and zaleplon), which were marketed as effective sleep aids and “not a benzodiazepine,” with the implication from sales representatives that, without having the molecular structure of benzodiazepines, they would not present the same rebound or adverse effects as benzodiazepines. However, the “Z-drug” agents are indeed benzodiazepine receptor agonists and are associated with the same downsides as agents in the true benzodiazepine drug class.
Benzodiazepine Withdrawal
Authors: Wright Steven L.
Published: November 2020

Benzodiazepines and related compounds (benzodiazepine receptor agonists [BzRAs]) cause a wide range of adverse reactions, including withdrawal symptoms, even when normal or low dosages are used. Deprescribing is recommended when there is loss of efficacy, major side effects, or use longer than four weeks. The withdrawal syndrome is due to physiologic dependence based on various receptor adaptations. Psychological, neurophysiologic, and somatic complaints can be misdiagnosed as psychiatric, psychosomatic, or substance use disorder. These symptoms may be severe and prolonged. The discontinuation process should include careful planning, support, and the use of cognitive behavioral therapy. Tapering, perhaps after substituting with a long-acting BzRA, should be patient-led and proceed slowly, anticipating completion over 12 to 18 months or even longer. In a proportion of patients, symptoms may continue months or years after complete BzRA cessation, requiring ongoing medical care.
Benzodiazepines and Pain Management
Authors: Peppin John F. , Wright Steven L.
Published: November 2020

Chronic pain is widespread and the use of opioids for chronic pain is also common. Frequently benzodiazepines are concomitantly prescribed in these patients, for anxiety, sleep disorders, and muscle pain and spasm. In the United States, Canada, and the European Union, increases in benzodiazepine prescribing has been seen, in some cases over 16% over the last decade. Unfortunately, the combination of opioids and benzodiazepines is correlated with overdose and overdose death. Few data exist to support the use of benzos for sleep, muscle spasm, or the long-term treatment of anxiety in the context of pain. It has been further shown that the use of benzodiazepines carries other adverse events and issues. It is estimated that the elimination of benzodiazepines would decrease overdoses by over 15%. The deprescribing of benzodiazepines should become common practice in the professional pain community and their use drastically limited. The authors suggest an approach to the discontinuation of benzodiazepines that includes extensive patient involvement. Other options for anxiety, sleep disturbances, and muscle relaxation are available and should be considered. For those already on these agents (legacy patients), tapering with the goal of discontinuation in a safe and person-centered process should be undertaken.
The Regulatory History of Benzodiazepines in the Age of the Dark Web and Other Threats
Authors: Coleman John J.
Published: November 2020

The US Congress enacted a tiered structure for controlling drugs based on relative abuse potential, which is commonly known as the Controlled Substances Act (CSA). The CSA codifies five levels, or schedules, to classify such problematic drugs, ranging from those that have no accepted medical utility (Schedule I) to those with known medical utility but having relative abuse potential ranging from low (Schedule V) to high (Schedule II). Unfortunately, the process that regulatory agencies use to assess the abuse potential of street drugs does not work as well or as reliably for medicinal substances. This chapter discusses these issues and summarizes the history of efforts by a variety of worldwide regulatory agencies to properly characterize the benzodiazepines and related drugs with regard to legitimate therapeutic use versus the public health risks posed by drugs with misuse/abuse potential. The inadequacy of some of the general approaches and some specific attempts are discussed. Also discussed are some of the unintended consequences resulting from uninformed, misguided, or misdirected efforts. New complications include the influx of counterfeit drugs from domestic and foreign sources, and the existence of the Dark Web.
Trauma
Authors: Greaves Ian , Porter Keith
Published: November 2020

This chapter starts with assessment and treatment of the time-critical trauma patient. It describes the primary survey in detail, with clear highlighted sections on areas of express concern or danger. The ‘two Hs’ and ‘two Ts’ of traumatic cardiac arrest are fully covered. The secondary survey is outlined, before moving on to specific forms of trauma and management. Head and neck injuries, maxillofacial injuries, chest injuries, abdominal and genitourinary trauma, bone and joint injuries are all covered, including causes, treatment, and potential problems. Regional injuries are then covered, including the upper limb, the wrist, finger fractures, pelvic injuries, and the lower limb. Complications of fractures are explained. Soft tissue injuries are also covered by region. Human and animal bites and tetanus-prone wounds, spinal injuries, amputation, blast and gunshot injuries, burns, and inhalation injuries are also explained.
Poisoning
Authors: Greaves Ian , Porter Keith
Published: November 2020

This chapter begins by describing the approach to the poisoned patient, including airway, breathing, circulation, disability, and exposure. Differential diagnoses and those that should be excluded are explained. Diagnostic clues and symptom complexes are tabulated. Different poisons are then covered in turn, with their general and clinical features and management strategies detailed. A second section on substance abuse follows. The presentation and management of commonly abused drugs are described, alongside a dictionary of street names.
Acute psychiatric emergencies
Authors: Greaves Ian , Porter Keith
Published: November 2020

This chapter covers acute psychiatric emergencies and the associated legal and care-related issues. It begins with patient assessment with both a mental and physical examination checklist. It lists the common organic causes of psychiatric illness, available local services, and risk factors for successful suicide attempts. The presentation and management of different psychiatric conditions is described, including psychosis, depression, mania, anxiety disorders, and personality disorders. The legal and ethical issues, including the 1983 and 2007 Mental Health Acts, are explained. Methods of managing the violent patient are also described.
Metabolic medicine
Authors: Clarke Rosemary E. J. , Meek Claire L. , Wierzbicki Anthony S.
Published: November 2020

This chapter outlines the basic science and theory of metabolic medicine required for MRCP Part 1, before addressing the clinical aspects of metabolic medicine for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables and boxes to highlight key facts.
Molecular medicine and genetics
Authors: Mirza Nasir Saeed , Pirmohamed Munir
Published: November 2020

This chapter outlines the basic science and theory of molecular medicine and genetics required for MRCP Part 1, before addressing the clinical aspects of molecular medicine and genetics for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables, and boxes to highlight key facts.
Radiological investigations and applications
Authors: Harvey Chris J. , O’Regan Declan
Published: November 2020

This chapter outlines the basic science and theory of radiological investigations and applications required for MRCP Part 1, before addressing the clinical aspects of radiological investigations and applications for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables, and boxes to highlight key facts.
Immunology
Authors: Yong Patrick
Published: November 2020

This chapter outlines the basic science and theory of Immunology required for MRCP Part 1, before addressing the clinical aspects of Immunology for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables and boxes to highlight key facts.
Cardiology
Authors: Holdsworth David , Williams Rupert P. , Gall Nicholas
Published: November 2020

This chapter outlines the basic science and theory of cardiology required for MRCP Part 1, before addressing the clinical aspects of cardiology for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables, and boxes to highlight key facts.
Diabetes and Endocrinology
Authors: Ballav Chitrabhanu , Clarke Sophie A. , Wass John
Published: November 2020

This chapter outlines the basic science and theory of diabetes and endocrinology required for MRCP Part 1, before addressing the clinical aspects of diabetes and endocrinology for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables, and boxes to highlight key facts.
Rheumatology
Authors: Nikiphorou Elena , Nuttall Anna , Bessant Rupa
Published: November 2020

This chapter outlines the basic science and theory of rheumatology required for MRCP Part 1, before addressing the clinical aspects of rheumatology for MRCP Part 2. To ensure effective revision, material is presented in short sections with bullet lists, tables, and boxes to highlight key facts.
Diagnosis, risk stratification, and therapeutic choices
Authors: Boterberg Tom , Cheesman Edmund , D’Arco Felice , Dieckmann Karin , Gaze Mark , Humphries Paul , Kelsey Anna , Olsen Øystein , Poppe Bruce , Roebuck Derek , Sethuraman Chitra , Speleman Frank , Vujanic Gordan
Published: November 2020

Chapter 3 discusses cancer diagnosis, risk stratification, and therapeutic choices in children and young people. Radiological investigations support the diagnosis and provide staging information for accurate risk stratification. Interventional radiology is useful for obtaining tissue for pathological examination. Histopathology and molecular studies define the precise tumour type and subtype and are used to confirm or rule out the presence of metastatic disease. Post-operative histopathology defines the extent of spread and is important for the staging of some tumours. Together, these findings inform multidisciplinary team discussion and help to identify the best treatment schedule. A significant proportion of cancers have a genetic basis, and it is important to identify these from the family history, predisposing syndromes, or tumour type. Modern molecular genomic techniques have made definitive diagnosis easier. Some genetic conditions lead to increased radiosensitivity and may predispose the patient to excessive radiation-related morbidity and a high risk of second primary tumours.
Design of the recovery room
Authors: Craig Anne , Hatfield Anthea
Published: November 2020

A traditional recovery room is described with clear instructions for setting out floor space, trolley bays, and nurses’ station. Diagrams and illustrations show the type of recovery room most commonly used with more imaginative designs also included.
The respiratory system
Authors: Craig Anne , Hatfield Anthea
Published: November 2020

This chapter discusses hypoxia and respiratory obstruction and the management of hypoventilation. Stridor and laryngospasm, laryngeal and vocal cord damage are described and ways of preventing these from occurring and treating them if they do occur are discussed. Aspiration and its complications and treatment are fully covered.
Cardiopulmonary resuscitation
Authors: Craig Anne , Hatfield Anthea
Published: November 2020

This chapter will teach you about basic and advanced life support, how to use and care for the defibrillator, and give you information about the drugs to use in emergencies. Read and learn this information thoroughly. Be ready to save a life if a cardiac arrest occurs.
The bleeding patient
Authors: Craig Anne , Hatfield Anthea
Published: November 2020

Part one of this chapter tells you about the physiology of blood and oxygen supply, about anaemia and tissue hypoxia, and the physiology of coagulation. Drugs that interfere with clotting are discussed. Bleeding, coagulation, and platelet disorders are covered as well as disseminated intravascular coagulation. Part two is concerned with bleeding in the recovery room: how to cope with rapid blood loss, managing ongoing blood loss, and how to use clotting profiles to guide treatment. There is also a section covering blood transfusion, blood groups and typing. Massive blood transfusion is clearly described, there are guidelines about when to use fresh frozen plasma, when to use platelets, and when to use cryoprecipitate. The final section of the chapter is about problems with blood transfusions.
A Two-Locus System with Strong Epistasis Underlies Rapid Parasite-Mediated Evolution of Host Resistance
Authors: Ameline Camille , Bourgeois Yann , Vögtli Felix , Savola Eevi , Andras Jason , Engelstädter Jan , Ebert Dieter
Published: November 2020

Parasites are a major evolutionary force, driving adaptive responses in host populations. Although the link between phenotypic response to parasite-mediated natural selection and the underlying genetic architecture often remains obscure, this link is crucial for understanding the evolution of resistance and predicting associated allele frequency changes in the population. To close this gap, we monitored the response to selection during epidemics of a virulent bacterial pathogen, Pasteuria ramosa, in a natural host population of Daphnia magna. Across two epidemics, we observed a strong increase in the proportion of resistant phenotypes as the epidemics progressed. Field and laboratory experiments confirmed that this increase in resistance was caused by selection from the local parasite. Using a genome-wide association study, we built a genetic model in which two genomic regions with dominance and epistasis control resistance polymorphism in the host. We verified this model by selfing host genotypes with different resistance phenotypes and scoring their F1 for segregation of resistance and associated genetic markers. Such epistatic effects with strong fitness consequences in host–parasite coevolution are believed to be crucial in the Red Queen model for the evolution of genetic recombination.
TRANSMISSION COEFFICIENT OF POWER DENSITY INTO SKIN TISSUE BETWEEN 6 AND 300 GHZ
Authors: Christ Andreas , Samaras Theodoros , Neufeld Esra , Kuster Niels
Published: November 2020

The latest electromagnetic safety guidelines define transmitted or epithelial power density as the basic restriction above 6 GHz. In this note, we derive an approximation for a conservative transmission coefficient for quasi plane wave incidence as a function of the frequency for the normal component of the Poynting vector with respect to the evaluation plane or tissue surface |Sz inc| and for its modulus ||Sinc||. The maximum transmission coefficient for the normal component of the Poynting vector ${\boldsymbol{T}}_{\mathbf{z}}^{\mathbf{max}}$ is 1 independent of tissue composition and frequency. Approximations of ${\boldsymbol{T}}_{\mathbf{total}}^{\mathbf{max}}$ normalized to ||Sinc|| for thin and thick stratum corneum are provided allowing higher exposures. These approximations allow to conservatively demonstrate compliance with basic restrictions when quasi plane-wave conditions are locally satisfied and enhancement effects of standing waves between source and body can be neglected. The reported results are important to regulators and standardization bodies regarding revisions of compliance requirements and safety guidelines.
Ovulation is Inhibited by an Environmentally Relevant Phthalate Mixture in Mouse Antral Follicles In Vitro
Authors: Land Katie L , Lane Madison E , Fugate Ava C , Hannon Patrick R
Published: November 2020

Phthalates are solvents and plasticizers found in consumer products including cosmetics, food/beverage containers, housing materials, etc. Phthalates are known endocrine-disrupting chemicals that can directly target the ovary, potentially causing defects in ovulation and fertility. Women are exposed to multiple different phthalates daily, therefore this study investigated the effects of an environmentally relevant phthalate mixture (PHTmix) on ovulation. Ovulation is initiated by the luteinizing hormone (LH) surge, which induces prostaglandin (PG) production, progesterone (P4)/progesterone receptor (PGR) signaling, and extracellular matrix (ECM) remodeling. We hypothesized that the PHTmix would directly inhibit ovulation by altering the levels of PGs, P4/PGR, and enzymes involved in ECM remodeling. Antral follicles from CD-1 mice were treated with vehicle control alone (dimethylsulfoxide, DMSO), hCG alone (LH analog), and hCG+PHTmix (1–500μg/ml), and samples were collected across the ovulatory period. The PHTmix decreased ovulation rates at all doses tested in a dose-dependent manner when compared to hCG. PG levels were decreased by the PHTmix when compared to hCG, which was potentially mediated by altered levels of PG synthesis (Ptgs2) and transport (Slco2a1) genes. The PHTmix altered P4 and Pgr levels when compared to hCG, leading to decreases in downstream PGR-mediated genes (Edn2, Il6, Adamts1). ECM remodeling was potentially dysregulated by altered levels of ovulatory mediators belonging to the matrix metalloproteases and plasminogen activator families. These data suggest that phthalate exposure inhibits ovulation by altering PG levels, P4/PGR action, and ECM remodeling.
Divergent RNA viruses in Macrophomina phaseolina exhibit potential as virocontrol agents
Authors: Wang Jing , Ni Yunxia , Liu Xintao , Zhao Hui , Xiao Yannong , Xiao Xueqiong , Li Shujun , Liu Hongyan
Published: November 2020

Macrophomina phaseolina is an important necrotrophic phytopathogenic fungus and cause extensive damage in many oilseed crops. Twelve M.phaseolina isolates with diverse biological phenotypes were selected for a high-throughput sequencing-based metatranscriptomic and bioinformatics analysis to identify viruses infecting M.phaseolina. The analysis identified 40 partial or nearly complete viral genome segments, 31 of which were novel viruses. Among these viral sequences, 43% of the viral genomes were double-stranded RNA (dsRNA), 47% were positive single-stranded RNA (ssRNA+), and the remaining 10% were negative sense-stranded RNA (ssRNA−). The 40 viruses showed affinity to 13 distinct viral lineages, including Bunyavirales (four viruses), Totiviridae (three viruses), Chrysoviridae (five viruses), Partitiviridae (four viruses), Hypoviridae (one virus), Endornaviridae (two viruses), Tombusviridae (three viruses), Narnaviridae (one virus), Potyviridae (one virus), Bromoviridae (one virus), Virgaviridae (six viruses), ‘Fusagraviridae’ (five viruses), and Ourmiavirus (four viruses). Two viruses are closely related to two families, Potyviridae and Bromoviridae, which previously contained no mycovirus species. Moreover, nine novel viruses associated with M.phaseolina were identified in the family Totiviridae, Endornaviridae, and Partitiviridae. Coinfection with multiple viruses is prevalent in M.phaseolina, with each isolate harboring different numbers of viruses, ranging from three to eighteen. Furthermore, the effects of the viruses on the fungal host were analyzed according to the biological characteristics of each isolate. The results suggested that M.phaseolina hypovirus 2, M.phaseolina fusagravirus virus 1-5 (MpFV1-5), M.phaseolina endornavirus 1-2 (MpEV1-2), M.phaseolina ourmia-like virus 1-3 (MpOLV1-3), M.phaseolina mitovirus 4 (MpMV4), and M.phaseolina mycobunyavirus 1-4 (MpMBV1-4) were only detected in hypovirulent isolates. Those viruses associated with hypovirulence might be used as biological control agents as an environmentally friendly alternative to chemical fungicides. These findings considerably expand our understanding of mycoviruses in M.phaseolina and unvailed the presence of a huge difference among viruses in isolates from different hosts in distant geographical regions. Together, the present study provides new knowledge about viral evolution and fungus-virus coevolution.
Outcomes of Patients With Nonunion After Open Tibial Shaft Fractures With or Without Soft Tissue Coverage Procedures
Authors: Egol Kenneth A. , Littlefield Connor P. , Walden Timothy , Leucht Philipp , Levine Jaime , Konda Sanjit
Published: November 2020

Objectives:

To evaluate the outcomes of patients who underwent soft tissue flap coverage during treatment of a tibia fracture nonunion.

Design:

Retrospective analysis on prospectively collected data.

Setting:

Academic medical center.

Patients/Participants:

One hundred fifty-seven patients were treated for a fracture nonunion after a tibia fracture over a 15-year period. Sixty-six patients had sustained an open tibial fracture initially and 25 of these patients underwent soft tissue flaps for their open tibia fracture nonunion.

Intervention:

Manipulation of soft tissue flaps, either placement or elevation for graft placement in ununited previously open tibial fractures.

Main Outcome Measurements:

Bony healing, time to union, ultimate soft tissue status, postoperative complications, and functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA). This group was compared with a group of open tibial fracture nonunions that did not undergo soft tissue transfer.

Results:

Bony healing was achieved in 24 of 25 patients (96.0%) who received flaps at a mean time to union of 8.7 ± 3.3 months compared with 39 of 41 patients (95.1%) at a mean 7.5 ± 3.2 months (P > 0.05) in the noncoverage group. Healing rate and time to union did not differ between groups. At latest follow-up, the flap coverage group reported a mean SMFA index of 17.1 compared with an SMFA index of 27.7 for the noncoverage group (P = 0.037).

Conclusions:

Utilization of soft tissue flaps in the setting of open tibia shaft nonunion repair surgery are associated with a high union rate (>90%). Coverage with or manipulation of soft tissue flaps did not result in improved bony healing rate or time to union compared with those who did not require flaps. However, soft tissue flap coverage was associated with higher functional scores at long-term follow-up.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina
Authors: Wohlmuth Christoph , Wohlmuth-Wieser Iris , Laframboise Stéphane
Published: November 2020

Objectives

The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort.

Materials and Methods

This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the “response criteria for use in trials testing immunotherapeutics” (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response.

Results

At a median follow-up of 37.8 months (5.8–110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%–49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%–72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients.

Conclusions

Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.
Building the Profession of the Future
Authors: Weberg Daniel
Published: November 2020

Leaders need to have a change framework in order to be successful in building the future of nursing. Health care leaders need to combine their knowledge of culture, technology, and the science of change in order to lead innovation in their organizations. Leaders should also understand the negative behaviors that stop change and kill innovation.
Heart Valve Abnormalities in Systemic Sclerosis Patients
Authors: Colaci Michele , Schinocca Claudia , Bosco Ylenia Dal , Ronsivalle Giuseppe , Guggino Giuliana , de Andres Ilenia , Russo Alessandra A. , Sambataro Domenico , Sambataro Gianluca , Malatino Lorenzo
Published: November 2020

Background

Systemic sclerosis (SSc) is a chronic autoimmune disease that is characterized by vasculopathy and fibrosis of the skin and visceral organs. Heart valve diseases are poorly described and generally not considered typical of SSc. We aimed to describe valvular abnormalities in a multicenter cohort of SSc patients and to investigate their correlation with SSc features.

Methods

We recruited 118 consecutive SSc patients (male/female, 14/104; mean age, 55.2 ± 12.1 years) in 3 rheumatology centers in Sicily, Italy, from January to October 2019.

Results

Mitral and tricuspid valve insufficiency was found in 85% and 91% of patients, respectively; regurgitations were generally mild and never severe. Mitral stenosis was rare (2%), and tricuspid stenosis was not observed. Sclerosis and calcification were present in 30% of mitral valves and in only 4% of tricuspid valves. The aortic valve was affected in 25% of cases, and it generally presented as regurgitation or sclerosis, whereas stenosis was rare (3%). Finally, 11% of SSc patients showed regurgitation of the pulmonary valve. No specific associations between SSc features and valve alterations were found.

Conclusions

Valvular diseases are frequently observed in SSc patients, with a predominant pattern of valvular regurgitations. Therefore, echocardiography should be routinely performed during SSc patient follow-up, considering the potential influence of additional cardiac involvement in the prognosis of these patients.
Dendrochronological dates confirm a Late Prehistoric population decline in the American Southwest derived from radiocarbon dates
Authors: Robinson Erick , Bocinsky R. Kyle , Bird Darcy , Freeman Jacob , Kelly Robert L.
Published: November 2020

The northern American Southwest provides one of the most well-documented cases of human population growth and decline in the world. The geographic extent of this decline in North America is unknown owing to the lack of high-resolution palaeodemographic data from regions across and beyond the greater Southwest, where archaeological radiocarbon data are often the only available proxy for investigating these palaeodemographic processes. Radiocarbon time series across and beyond the greater Southwest suggest widespread population collapses from AD 1300 to 1600. However, radiocarbon data have potential biases caused by variable radiocarbon sample preservation, sample collection and the nonlinearity of the radiocarbon calibration curve. In order to be confident in the wider trends seen in radiocarbon time series across and beyond the greater Southwest, here we focus on regions that have multiple palaeodemographic proxies and compare those proxies to radiocarbon time series. We develop a new method for time series analysis and comparison between dendrochronological data and radiocarbon data. Results confirm a multiple proxy decline in human populations across the Upland US Southwest, Central Mesa Verde and Northern Rio Grande from AD 1300 to 1600. These results lend confidence to single proxy radiocarbon-based reconstructions of palaeodemography outside the Southwest that suggest post-AD 1300 population declines in many parts of North America.

This article is part of the theme issue ‘Cross-disciplinary approaches to prehistoric demography’.
Sometimes hidden but always there: the assumptions underlying genetic inference of demographic histories
Authors: Loog Liisa
Published: November 2020

Demographic processes directly affect patterns of genetic variation within contemporary populations as well as future generations, allowing for demographic inference from patterns of both present-day and past genetic variation. Advances in laboratory procedures, sequencing and genotyping technologies in the past decades have resulted in massive increases in high-quality genome-wide genetic data from present-day populations and allowed retrieval of genetic data from archaeological material, also known as ancient DNA. This has resulted in an explosion of work exploring past changes in population size, structure, continuity and movement. However, as genetic processes are highly stochastic, patterns of genetic variation only indirectly reflect demographic histories. As a result, past demographic processes need to be reconstructed using an inferential approach. This usually involves comparing observed patterns of variation with model expectations from theoretical population genetics. A large number of approaches have been developed based on different population genetic models that each come with assumptions about the data and underlying demography. In this article I review some of the key models and assumptions underlying the most commonly used approaches for past demographic inference and their consequences for our ability to link the inferred demographic processes to the archaeological and climate records.

This article is part of the theme issue ‘Cross-disciplinary approaches to prehistoric demography’.
Flavobacterium bizetiae sp. nov., isolated from diseased freshwater fish in Canada at the end of the 1970s
Authors: Mühle Estelle , Abry Chloé , Leclerc Priscilla , Goly Gogoa-Marthe , Criscuolo Alexis , Busse Hans-Jürgen , Kämpfer Peter , Bernardet Jean-François , Clermont Dominique , Chesneau Olivier
Published: November 2020

Genome sequence analysis of two strains collected in Canada at the end of the 1970s and deposited in 1998 at the Collection de l’Institut Pasteur has led to the taxonomic description of a novel fish-associated species in the genus

Flavobacterium

. Both strains, CIP 105534T and CIP 105535, were yellow-pigmented, Gram-stain-negative, non-spore-forming rod-shaped bacteria that exhibited gliding motility. They grew aerobically in a temperature range from 5 to 30 °C with optimal growth at 25 °C on trypticase soy or Reasoner's 2A agar but they did not grow on marine agar. Their major fatty acid profiles were similar, consisting of iso-C15 : 0, C16 : 1 ω7c and/or iso-C15 : 0 2-OH (shown as summed feature 3), C16 : 0 3-OH, iso-C17 : 0 3-OH and C16 : 0. The major polyamine was sym-homospermidine. Phosphatidylethanolamine and, most notably, ornithine-containing lipid OL2 and unidentified aminophospholipid APL1 were major polar lipids. A yellow pigment spot was visible after chromatographic analysis. The predominant respiratory quinone was MK-6. The G+C content of the two genomes was 34 mol% and their size was around 5.8 Mb. Comparison of the 16S rRNA gene sequences with those of the closely related type strains showed high levels of relatedness with

Flavobacterium collinsii

and

Flavobacterium pectinovorum

. All average nucleotide identity (ANI) and digital DNA–DNA hybridization values estimated against publicly available

Flavobacterium

genome assemblies were lower than 90 and 30 %, respectively. Phylogenetic, phenotypic and chemotaxonomic data indicated that the two strains represent a novel species of the genus

Flavobacterium

, for which the name Flavobacterium bizetiae sp. nov. is proposed. The type strain is CIP 105534T (=LMG 1342T). The unique ability of F. bizetiae to use melibiose as a sole source of carbon could provide a simple phenotypic test to discriminate F. bizetiae from its closest relatives.
Clostridium fessum sp. nov., isolated from human faeces
Authors: Seo Boram , Jeon Kyungchan , Baek Inwoo , Lee Yung Mi , Baek Kiwoon , Ko GwangPyo
Published: November 2020

An obligately anaerobic, Gram-stain-positive and spore-forming strain, SNUG30386T was isolated from a faecal sample of a healthy Korean subject. The strain formed a round ivory-coloured colony and cells were chained rods with tapered ends, approximately 2.0–2.5×0.6–0.8 μm in size. The taxonomic analysis indicated that strain SNUG30386T was within the family

Lachnospiraceae

. According to the 16S rRNA gene sequence similarity, the closest species to strain SNUG30386T was

Clostridium symbiosum

(95.6 %), followed by

Enterocloster asparagiformis

(94.8 %),

Enterocloster clostridioformis

(94.8 %) and

Enterocloster lavalensis

(94.6 %). The evolutionary tree based on 16S rRNA gene sequences demonstrated that strain SNUG30386T had split apart at a unique branch point far from other close relatives. Its DNA G+C content was 48.3 mol% calculated from the whole genome sequence. The major cellular fatty acids were C16 : 0 and C14 : 0. Compared to those of the closely related species, strain SNUG30386T showed distinct biochemical activities such as being unable to utilize most of carbon sources except d-glucose and l-arabinose. As a result, based on its unique phylogenetic clade and taxonomic characteristics, we conclude that strain SNUG30386T represents a novel species within the genus

Clostridium

, for which the name Clostridium fessum sp. nov. is proposed. The type strain of the novel species is SNUG30386T (=KCTC 15633T= JCM 32258T).
Glycomyces terrestris sp. nov., isolated from extremely arid soil from Yuanmou Earth Forest
Authors: Li Qinyuan , Li Guiding , Lang Lei , An Defeng , Jiang Chenglin , Jiang Yi
Published: November 2020

A Gram-stain-positive, mycelium-forming actinobacterium, YIM 121974T was isolated from an extreme arid soil sample collected at Yuanmou Earth Forest, Yunnan Province, PR China. Classification using a polyphasic approach suggested that strain YIM 121974T belonged to the genus

Glycomyces

and was closely related to

Glycomyces dulcitolivorans

SJ-25T (98.3 %),

Glycomyces scopariae

YIM 56256T (98 %),

Glycomyces mayteni

YIM 61331T (97.9 %),

Glycomyces albidus

NEAU-7082T (97.9 %),

Glycomyces sambucus

CGMCC 4.3147T (97.7 %),

Glycomyces artemisiae

IXS4T (97.6 %) and Glycomyces parisis CPCC 204357T (97.5 %), but could be distinguished from its closest relatives by a combination of phenotypic and phylogenetic features. Average nucleotide identity values of YIM 121974T to its closest phylogenetic neighbours were 70.7–88.9 %, which are lower than the threshold of 95 %. The digital DNA–DNA hybridization values between YIM 121974T and these relative species were 18.0–36.3 %, which are also well below the cut-off value (>70 %) for species delineation. The DNA G+C content of strain YIM 121974T was 72.3 mol% (draft genome sequence). The predominant menaquinone was MK-11. The phospholipids were composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, phosphoglycolipid and glycolipid. The major fatty acid compositions were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The draft genome of isolate YIM 121974T was found to contain 11 secondary metabolite biosynthesis gene clusters by using the antiSMASH server. Based on the above observations, strain YIM 121974T could be distinguished from closely related species belonging to the genus

Glycomyces

. Thus, strain YIM 121974T represents a novel species of the genus

Glycomyces

, for which the name Glycomyces terrestris sp. nov. is proposed. The type strain is YIM 121974T (=KCTC 39870T=DSM 106742T).
Genomic diversity of Escherichia coli isolates from backyard chickens and guinea fowl in the Gambia
Authors: Foster-Nyarko Ebenezer , Alikhan Nabil-Fareed , Ravi Anuradha , Thomson Nicholas M. , Jarju Sheikh , Kwambana-Adams Brenda A. , Secka Arss , O’Grady Justin , Antonio Martin , Pallen Mark John
Published: November 2020

Chickens and guinea fowl are commonly reared in Gambian homes as affordable sources of protein. Using standard microbiological techniques, we obtained 68 caecal isolates of

Escherichia coli

from 10 chickens and 9 guinea fowl in rural Gambia. After Illumina whole-genome sequencing, 28 sequence types were detected in the isolates (4 of them novel), of which ST155 was the most common (22/68, 32 %). These strains span four of the eight main phylogroups of E. coli, with phylogroups B1 and A being most prevalent. Nearly a third of the isolates harboured at least one antimicrobial resistance gene, while most of the ST155 isolates (14/22, 64 %) encoded resistance to ≥3 classes of clinically relevant antibiotics, as well as putative virulence factors, suggesting pathogenic potential in humans. Furthermore, hierarchical clustering revealed that several Gambian poultry strains were closely related to isolates from humans. Although the ST155 lineage is common in poultry from Africa and South America, the Gambian ST155 isolates belong to a unique cgMLST cluster comprising closely related (38–39 alleles differences) isolates from poultry and livestock from sub-Saharan Africa – suggesting that strains can be exchanged between poultry and livestock in this setting. Continued surveillance of

E. coli

and other potential pathogens in rural backyard poultry from sub-Saharan Africa is warranted.