Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine.

As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.

The Concept of Treatment-Refractory Addiction: Implications for Addiction Treatment Systems and Research.

The concept of treatment-refractory addiction, proposed by Eric Strain in this edition of the Journal, has the potential to invigorate the field of addiction treatment and research by focusing on a phenomenon that is familiar to any clinician treating patients with substance use disorders, namely, the patient who does not experience sufficient improvement from standard treatments. An analogy is drawn to the concept of treatment-resistant depression and the STAR*D study, which demonstrated an algorithmic approach to treatment, where if the first antidepressant medication tried did not result in remission from depression, subsequent trials of medications or cognitive behavioral therapy doubled the proportion of patients achieving remission. Recognizing treatment-refractory addiction challenges our field to develop analogous, stepwise, algorithmic approaches to treatment of substance use disorders, moving away from siloed treatment programs toward integrated treatment systems where alternative treatments are available, offering the kind of personalized, tailored forms of care used in the treatment of most other chronic illnesses.

Delayed identification of compound heterozygous (Phe508del/Arg117His) cystic fibrosis variants in a patient awaiting liver transplantation.

A man in his 60s undergoing liver transplant assessment was referred to the respiratory team after a thoracic CT scan revealed diffuse tree-in-bud changes. He had a history of infertility, chronic pancreatitis and liver cirrhosis with portal hypertension. Broncho-alveolar lavage was positive for Genetic screening found two cystic fibrosis transmembrane conductance regulator variants: Phe508del and Arg117His-7T.

Demonstration of an app-delivered digital therapeutic program for methamphetamine use disorder.

This study assessed the feasibility and utility of a digital, all-virtual program designed for treatment of methamphetamine use disorder (MUD). Forty-nine adults with moderate- to severe-level MUD (per DSM-5 criteria) commenced the 8-week intervention. All aspects of the program were delivered via smartphone-based app.

Idiopathic pulmonary fibrosis: airway volume measurement identifies progressive disease on computed tomography scans.

http://bit.ly/2M8KVLl.

Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.

Alanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation.

Use and Misuse of Opioids in Chronic Pain.

The prescribing of opioid analgesics for pain management-particularly for management of chronic noncancer pain (CNCP)-has increased more than fourfold in the United States since the mid-1990s. Yet there is mounting evidence that opioids have only limited effectiveness in the management of CNCP, and the increased availability of prescribed opioids has contributed to upsurges in opioid-related addiction cases and overdose deaths. These concerns have led to critical revisiting and modification of prior pain management practices (e.

Substance Misuse and Substance use Disorders: Why do they Matter in Healthcare?

This paper first introduces important conceptual and practical distinctions among three key terms: substance "use," "misuse," and "disorders" (including addiction), and goes on to describe and quantify the important health and social problems associated with these terms. National survey data are presented to summarize the prevalence and varied costs associated with misuse of alcohol, illegal drugs, and prescribed medications in the United States. With this as background, the paper then describes historical views, perspectives, and efforts to deal with substance misuse problems in the United States and discusses how basic, clinical, and health service research, combined with recent changes in healthcare legislation and financing, have set the stage for a more effective, comprehensive public health approach.

Use of the Internet to Obtain Drugs without a Prescription Among Treatment-involved Adolescents and Young Adults.

Nonmedical use of prescription drugs is common and poses risks such as injury, overdose, and development of abuse and dependence. Internet pharmacies offer prescription drugs without a prescription, creating a source of illicit drugs accessible to anyone with an Internet connection. We examined this issue in a convenience sample of 1,860 adolescents and young adults from 24 residential and outpatient treatment programs.

How Should Remote Clinical Monitoring Be Used to Treat Alcohol Use Disorders?: Initial Findings From an Expert Round Table Discussion.

Scientific evidence combined with new health insurance coverage now enable a chronic illness management approach to the treatment of alcohol use disorders (AUDs), including regular monitoring of blood alcohol content (BAC), as a useful indicator of disease control. Recent technical advances now permit many different types of remote, real-time monitoring of BAC. However, there is no body of research to empirically guide clinicians in how to maximize the clinical potential of remote BAC monitoring.

Converging advances in science, policy and public awareness: A time of great opportunity and change in addiction treatment.

Scientific advances, increased public awareness about addiction as a disease, and significant changes in public policy have led to transformational changes in this field. Preclinical and clinical studies highlighted in this issue have supported the emerging concept of substance use disorders as a novel major concern within the healthcare community. In this Commentary, we discuss the potential impact of recent legislation (Affordable Care Act and the Mental Health Parity and Addiction Equity Act) when fully implemented to end the real and perceived segregation of addiction and substance abuse disorders from mainstream healthcare and insurance reimbursement.

Conundrum in an asthma exacerbation.

A 66-year-old man, an asthmatic, presented with symptoms suggestive of an acute exacerbation of asthma. His arterial blood gas revealed type 1 respiratory failure (PaO2 <8 kPa or 60 mm Hg with normal or low PaCO2) with a compensated lactic acidosis. He was treated for an asthma exacerbation and sepsis.

Assessing Adolescent Substance Abuse Programs with Updated Quality Indicators: The Development of a Consumer Guide for Adolescent Treatment.

When adolescent substance abuse requires treatment, few parents know which treatment features are important and which treatment programs are effective. There are few resources to help them select appropriate care. We describe early work on an evaluation method and comparative treatment guide for parents based upon the premise that the quality of a program and its potential effectiveness is a function of the number and frequency of evidence-based treatment practices (EBPs) delivered.

Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4.

Phosphodiesterase 4 (PDE4) is an essential contributor to intracellular signaling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain. Alternative promoters, transcriptional start sites, and mRNA splicing lead to the existence of over 25 variants of PDE4, broadly classified as long, short, and supershort forms.

The affordable care act and treatment for "substance use disorders:" implications of ending segregated behavioral healthcare.

The Affordable Care Act (2010) and the Mental Health Parity and Addiction Equity Act (2008) are expected to transform substance abuse prevention and treatment in the United States. In this paper, we outline the potential disruption to the existing specialty care delivery system, and describe the opportunities for treatment providers and health services researchers.