A child with a neuronal ceroid lipofuscinosis was found to carry loss-of-function mutations in the gene
MFSD8
(
CLN7
). A year after genetic diagnosis, the child began treatment with an ...oligonucleotide drug that was designed to correct the aberrant pre–messenger RNA splicing caused by one of these mutations.
Opioid use disorder (OUD) is a chronic relapsing disorder that, whilst initially driven by activation of brain reward neurocircuits, increasingly engages anti-reward neurocircuits that drive adverse ...emotional states and relapse. However, successful recovery is possible with appropriate treatment, although with a persisting propensity to relapse. The individual and public health burdens of OUD are immense; 26.8 million people were estimated to be living with OUD globally in 2016, with >100,000 opioid overdose deaths annually, including >47,000 in the USA in 2017. Well-conducted trials have demonstrated that long-term opioid agonist therapy with methadone and buprenorphine have great efficacy for OUD treatment and can save lives. New forms of the opioid receptor antagonist naltrexone are also being studied. Some frequently used approaches have less scientifically robust evidence but are nevertheless considered important, including community preventive strategies, harm reduction interventions to reduce adverse sequelae from ongoing use and mutual aid groups. Other commonly used approaches, such as detoxification alone, lack scientific evidence. Delivery of effective prevention and treatment responses is often complicated by coexisting comorbidities and inadequate support, as well as by conflicting public and political opinions. Science has a crucial role to play in informing public attitudes and developing fuller evidence to understand OUD and its associated harms, as well as in obtaining the evidence today that will improve the prevention and treatment interventions of tomorrow.
Cancer and its treatment produce deleterious symptoms across the phases of care. Poorly controlled symptoms negatively affect quality of life and result in increased health-care needs and ...hospitalization. The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium was created to develop 3 large-scale, systematic symptom management systems, deployed through electronic health record platforms, and to test them in pragmatic, randomized, hybrid effectiveness and implementation trials. Here, we describe the IMPACT Consortium's conceptual framework, its organizational components, and plans for evaluation. The study designs and lessons learned are highlighted in the context of disruptions related to the COVID-19 pandemic.
Mechanistic insight is gained for saccharide transport through plasticized cellulose triacetate (CTA) membranes containing lipophilic ion-pair transport carriers. The molecular structures of the ...different membrane components are systematically varied and diagnostic transport characteristics such as saccharide–carrier diffusion constant and saccharide extraction constant are determined. The observed percolation thresholds support a jumping mechanism, however, the diffusion constants are found to decrease as the size of the saccharide, carrier cation, and carrier anion increase, indicating that the rate-limiting step in the transport process involves diffusion of a complex comprised of all three components. The data is reconciled in terms of mobile-site jumping mechanism where the saccharide is relayed along a sequence of ion-pair carriers that are locally mobile. In an attempt to improve saccharide selectivity, calix-4-arene dicarboxylates were evaluated as potential ditopic transport carriers. This produced no major change in saccharide extraction constants.
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