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COVID-19 and women
Early signs are that the COVID-19 virus poses a greater direct health risk to men, and particularly older men. But the pandemic is exposing and exploiting inequalities of all kinds, including gender inequality. In the long term, its impact on women’s health, rights and freedoms could harm us all.
Reading the COVID-19 market
Though I have spent nearly 40 years studying financial markets, I find them as bewildering, complex and fascinating as ever.
The conspiratorial style in pandemic politics
Over half of the world’s population is in self-confinement as a result of the COVID-19 pandemic. And though the lockdown has slowed the spread of the coronavirus, it has accelerated the progress of another insidious phenomenon: conspiracy theories.
The virus that changed the world
The COVID-19 pandemic has mercilessly exposed the weaknesses of institutions upon which the overwhelming majority of the world’s people rely.
COVID-19, conflict and fragility
Covid19 has hit hard on the public health and economic well-being of not only higher income but also higher-governance-capacity countries indicating the vulnerability of some of the wealthiest and most stable states to the fundamental interruptions instigated by an unexpected pandemic.
The day after tomorrow
When (and how) to end the COVID-19 lockdown has become the leading political question in every afflicted country.
The victor who lost the USSR
Thirty-five years ago, Mikhail Gorbachev was named general secretary of the Communist Party of the Soviet Union.
Case 2: Mysterious Hyperkalemia in a Premature Infant of 25 Weeks Gestation
Case 1: Neonatal Trauma Following Motor Vehicle Collision in Pregnancy
Tracheostomy in Infants in the Neonatal Intensive Care Unit
Approximately half of all pediatric tracheostomies are performed in infants younger than 1 year. Most tracheostomies in patients in the NICU are performed in cases of chronic respiratory failure requiring prolonged mechanical ventilation or upper airway obstruction. With improvements in ventilation and management of long-term intubation, indications for tracheostomy and perioperative management in this population continue to evolve. Evidence-based protocols to guide routine postoperative care, prevent and manage tracheostomy emergencies including accidental decannulation and tube obstruction, and attempt elective decannulation are sparse. Clinician awareness of safe tracheostomy practices and larger, prospective studies in infants are needed to improve clinical care of this vulnerable population.
Neonatal Vocal Fold Paralysis
Vocal fold paralysis (VFP) is an important cause of respiratory and feeding compromise in infants. The causes of neonatal VFP are varied and include central nervous system disorders, birth-related trauma, mediastinal masses, iatrogenic injuries, and idiopathic cases. Bilateral VFP often presents with stridor or respiratory distress and can require rapid intervention to stabilize an adequate airway. Unilateral VFP presents more subtly with a weak cry, swallowing dysfunction, and less frequently respiratory distress. The etiology and type of VFP is important for management. Evaluation involves direct visualization of the vocal folds, with additional imaging and testing in select cases. Swallowing dysfunction, also known as dysphagia, is very common in infants with VFP. A clinical assessment of swallowing function is necessary in all cases of VFP, with some patients also requiring an instrumental swallow assessment. Modification of feeding techniques and enteral access for feedings may be necessary. Airway management can vary from close monitoring to noninvasive ventilation, tracheostomy, and laryngeal surgery. Long-term follow-up with otolaryngology and speech-language pathology service is necessary for all children with VFP to ensure adequate breathing, swallowing, and phonation. The short- and long-term health and quality-of-life consequences of VFP can be substantial, especially if not managed early.
Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach
Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.
Neonatal Management During the Coronavirus Disease (COVID-19) Outbreak: The Chinese Experience
More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder [Review Articles]
Tobacco use is a persistent public health issue. It kills up to half its users and is the cause of nearly 90% of all lung cancers. The main psychoactive component of tobacco is nicotine, primarily responsible for its abuse-related effects. Accordingly, most pharmacotherapies for smoking cessation target nicotinic acetylcholine receptors (nAChRs), nicotine’s major site of action in the brain. The goal of the current review is twofold: first, to provide a brief overview of the most commonly used behavioral procedures for evaluating smoking cessation pharmacotherapies and an introduction to pharmacokinetic and pharmacodynamic properties of nicotine important for consideration in the development of new pharmacotherapies; and second, to discuss current and potential future pharmacological interventions aimed at decreasing tobacco use. Attention will focus on the potential for allosteric modulators of nAChRs to offer an improvement over currently approved pharmacotherapies. Additionally, given increasing public concern for the potential health consequences of using electronic nicotine delivery systems, which allow users to inhale aerosolized solutions as an alternative to smoking tobacco, an effort will be made throughout this review to address the implications of this relatively new form of nicotine delivery, specifically as it relates to smoking cessation.
Despite decades of research that have vastly improved our understanding of nicotine and its effects on the body, only a handful of pharmacotherapies have been successfully developed for use in smoking cessation. Thus, investigation of alternative pharmacological strategies for treating tobacco use disorder remains active; allosteric modulators of nicotinic acetylcholine receptors represent one class of compounds currently under development for this purpose.
Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution [Review Articles]
Before it was molecularly cloned in 1994, acute-phase response factor or signal transducer and activator of transcription (STAT)3 was the focus of intense research into understanding the mammalian response to injury, particularly the acute-phase response. Although known to be essential for liver production of acute-phase reactant proteins, many of which augment innate immune responses, molecular cloning of acute-phase response factor or STAT3 and the research this enabled helped establish the central function of Janus kinase (JAK) family members in cytokine signaling and identified a multitude of cytokines and peptide hormones, beyond interleukin-6 and its family members, that activate JAKs and STAT3, as well as numerous new programs that their activation drives. Many, like the acute-phase response, are adaptive, whereas several are maladaptive and lead to chronic inflammation and adverse consequences, such as cachexia, fibrosis, organ dysfunction, and cancer. Molecular cloning of STAT3 also enabled the identification of other noncanonical roles for STAT3 in normal physiology, including its contribution to the function of the electron transport chain and oxidative phosphorylation, its basal and stress-related adaptive functions in mitochondria, its function as a scaffold in inflammation-enhanced platelet activation, and its contributions to endothelial permeability and calcium efflux from endoplasmic reticulum. In this review, we will summarize the molecular and cellular biology of JAK/STAT3 signaling and its functions under basal and stress conditions, which are adaptive, and then review maladaptive JAK/STAT3 signaling in animals and humans that lead to disease, as well as recent attempts to modulate them to treat these diseases. In addition, we will discuss how consideration of the noncanonical and stress-related functions of STAT3 cannot be ignored in efforts to target the canonical functions of STAT3, if the goal is to develop drugs that are not only effective but safe.
Key biological functions of Janus kinase (JAK)/signal transducer and activator of transcription (STAT)3 signaling can be delineated into two broad categories: those essential for normal cell and organ development and those activated in response to stress that are adaptive. Persistent or dysregulated JAK/STAT3 signaling, however, is maladaptive and contributes to many diseases, including diseases characterized by chronic inflammation and fibrosis, and cancer. A comprehensive understanding of JAK/STAT3 signaling in normal development, and in adaptive and maladaptive responses to stress, is essential for the continued development of safe and effective therapies that target this signaling pathway.