Theoretical components of smoking cessation interventions for persons with physical disabilities: A scoping review.

Rationale Persons with physical disabilities report higher cigarette smoking rates and a lower likelihood of accessing health services (e.g., smoking cessation services). Explicit and systematic application of behaviour change theory may be a promising approach to addressing these inequities and developing impactful smoking cessation interventions for persons with physical disabilities. OBJECTIVE: This scoping review aimed to explore how behaviour change theory and intervention components have been used to design smoking cessation interventions for persons with physical disabilities. METHODS: Electronic databases (Medline, Embase, PsycINFO, CINAHL, Web of Science) were systematically searched. Smoking cessation interventions for persons with physical disabilities were identified. Behaviour change theory and intervention components, including behaviour change techniques, intervention functions, mode of delivery, intervention source, and setting, were extracted from the included articles. RESULTS: Among the eleven included articles, there were nine unique smoking cessation interventions for persons with physical disabilities. Three interventions mentioned theory, but none of these articles explicitly applied or tested the theory. Intervention components were consistently combined to deliver pharmacotherapy and behavioural counselling-based interventions. CONCLUSION: The results of this review highlight the scarcity of theory-based smoking cessation interventions for persons with physical disabilities. While the interventions were not theory-based, they were evidence-based and aligned with recommendations for smoking cessation treatment (i.e., behavioural counselling plus pharmacotherapy). Future research should take a theory-based approach to intervention development to enhance the likelihood that smoking cessation interventions for persons with physical disabilities are effective, replicable, and equitable.

Widely assumed phenotypic associations in Cannabis sativa lack a shared genetic basis.

The flowering plant Cannabis sativa, cultivated for centuries for multiple purposes, displays extensive variation in phenotypic traits in addition to its wide array of secondary metabolite production. Notably, Cannabis produces two well-known secondary-metabolite cannabinoids: cannabidiolic acid (CBDA) and delta-9-tetrahydrocannabinolic acid (THCA), which are the main products sought by consumers in the medical and recreational market. Cannabis has several suggested subspecies which have been shown to differ in chemistry, branching patterns, leaf morphology and other traits. In this study we obtained measurements related to phytochemistry, reproductive traits, growth architecture, and leaf morphology from 297 hybrid individuals from a cross between two diverse lineages. We explored correlations among these characteristics to inform our understanding of which traits may be causally associated. Many of the traits widely assumed to be strongly correlated did not show any relationship in this hybrid population. The current taxonomy and legal regulation within Cannabis is based on phenotypic and chemical characteristics. However, we find these traits are not associated when lineages are inter-crossed, which is a common breeding practice and forms the basis of most modern marijuana and hemp germplasms. Our results suggest naming conventions based on leaf morphology do not correspond to the chemical properties in plants with hybrid ancestry. Therefore, a new system for identifying variation within Cannabis is warranted that will provide reliable identifiers of the properties important for recreational and, especially, medical use.

The allosteric modulation of complement C5 by knob domain peptides.

Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. Allosteric mechanisms predominated, with one peptide selectively inhibiting C5 cleavage by the alternative pathway C5 convertase, revealing a targetable mechanistic difference between the classical and alternative pathway C5 convertases. Taking a hybrid biophysical approach, we present C5-knob domain co-crystal structures and, by solution methods, observed allosteric effects propagating >50 Å from the binding sites. This study expands the therapeutic scope of C5, presents new inhibitors, and introduces knob domains as new, low molecular weight antibody fragments, with therapeutic potential.

Antibodies are proteins produced by the immune system that can selectively bind to other molecules and modify their behaviour. Cows are highly equipped at fighting-off disease-causing microbes due to the unique shape of some of their antibodies. Unlike other jawed vertebrates, cows' antibodies contain an ultra-long loop region that contains a 'knob domain' which sticks out from the rest of the antibody. Recent research has shown that when detached, the knob domain behaves like an antibody fragment, and can independently bind to a range of different proteins. Antibody fragments are commonly developed in the laboratory to target proteins associated with certain diseases, such as arthritis and cancer. But it was unclear whether the knob domains from cows' antibodies could also have therapeutic potential. To investigate this, Macpherson et al. studied how knob domains attach to complement C5, a protein in the inflammatory pathway which is a drug target for various diseases, including severe COVID-19. The experiments identified various knob domains that bind to complement C5 and inhibits its activity by altering its structure or movement. Further tests studying the structure of these interactions, led to the discovery of a common mechanism by which inhibitors can modify the behaviour of this inflammatory protein. Complement C5 is involved in numerous molecular pathways in the immune system, which means many of the drugs developed to inhibit its activity can also leave patients vulnerable to infection. However, one of the knob domains identified by Macpherson et al. was found to reduce the activity of complement C5 in some pathways, whilst leaving other pathways intact. This could potentially reduce the risk of bacterial infections which sometimes arise following treatment with these types of inhibitors. These findings highlight a new approach for developing drug inhibitors for complement C5. Furthermore, the ability of knob domains to bind to multiple sites of complement C5 suggests that this fragment could be used to target proteins associated with other diseases.

Reviewer Recognition.

In this issue we would like to thank all those listed below for taking the time to review for IJIR: Your Sexual Medicine Journal in 2019 - your generosity is much appreciated and we hope your association with the journal continues in the future.

Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach.

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.

Effect of sleep deprivation on the human metabolome.

Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcarnitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation.