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The article goes on to describe the critical realist approach towards 'depth ontology' and 'generative causation'. It provides examples of how this approach is deployed in critical realist reviews and discourse analysis of drug policy. It concludes by arguing that critical realism enables more deeply explanatory, methodologically eclectic and democratically inclusive analysis of drug policy development and effects.Steroidal glycoalkaloids (SGAs) are defense specialized metabolites produced by thousands of Solanum species. These metabolites are remarkable in structural diversity formed following modifications in their core scaffold. In recent years, it became clear that a large portion of this chemical repertoire was acquired through various molecular mechanisms involving 'hijacking' of core metabolism enzymes. This was typically accompanied by gene duplication and divergence and further neofunctionalization as well as modified subcellular localization and evolution of new substrate preferences. In this review, we highlight recent findings in the SGAs biosynthetic pathway and elaborate on similar occurrences in other chemical classes that enabled evolution of specialized metabolic pathways and its underlying structural diversity.Background School health systems are increasingly investing in telemedicine platforms to address acute and chronic illnesses. Asthma, the most common chronic illness in childhood, is of particular interest given its high burden on school absenteeism. Objectives Conduct a systematic review evaluating impact of school-based telemedicine programs on improving asthma-related outcomes. Data sources PubMed, Cochrane CENTRAL, CINAHL, ERIC, PsycINFO, Embase, and Google Scholar STUDY ELIGIBILITY CRITERIA Original research, including quasi-experimental studies, without restriction on the type of telemedicine. Participants School-aged pediatric patients with asthma and their families. Interventions School-based telemedicine. Study appraisal and synthesis methods Two authors independently screened each abstract, conducted full-text review, assessed study quality, and extracted information. A third author resolved disagreements. Results Of 371 articles identified, 7 were included for the review. Outcomes of interest were asthma symptom-free days, asthma symptom frequency, quality-of-life, healthcare utilization, school absences, and spirometry. 4/7 studies reported significant increases in symptom-free days and/or decrease in symptom frequency. 5/6 reported increases in at least one quality-of-life metric, 2/7 reported a decrease in at least one healthcare utilization metric, 1/3 showed reductions in school absences, and 1/2 reported improvements in spirometry measures. Limitations Variability in intervention designs and outcome measures make comparisons and quantitative analyses across studies difficult. Only 2/7 studies were randomized controlled trials. Conclusions and implications of key findings High-quality evidence supporting the use of school-based telemedicine programs to improve patient outcomes is limited. While available evidence suggests benefit, only two comparative trials were identified, and the contribution of telemedicine to these studies' results is unclear.Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. The network-level mechanisms contributing to the effect exerted by DBS on the CT (CT-DBS) remain unknown. Combining CT-DBS with functional magnetic resonance imaging (fMRI), this study explored brain areas activated while applying CT-DBS in rats, using a newly developed neural probe that was compatible with MRI and could minimize the image distortion and resolve safety issues. Results showed activation of the anterior cingulate cortex, motor cortex, primary and secondary somatosensory cortices, caudate putamen, hypothalamus, thalamus, and hippocampus, suggesting that the corticostriatal, corticolimbic, and thalamocortical brain networks were affected. Behaviorally, the CT-DBS group required a shorter time than sham controls to learn a water-reward lever-pressing task and made more correct choices in a T-maze task. Abiraterone cost Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.Rich repertoires of movements underlie the complex social interactions of mammals. The building blocks, or syllables, of these movements are produced by spinal cord circuits that are comprised of diverse neuronal types that control musculoskeletal systems comprised of multi-segmented limbs. Together, these systems provide mammals with the evolutionary advantages of power, speed, and endurance. Here, I propose that the key steps in chordate evolution that led to these traits began with the development of the notochord and a proliferative ventricular zone (with associated Notch signalling). This step led to the production of diverse neuronal types that included the development of a sympathetic nervous system that could regulate the evolving cardiovascular system. And the sympathetic nervous system in turn led to the development of homeothermic endothermy, a requirement for motor systems to produce a combination of power, speed, and endurance. Furthermore, the evolution of the continuous structure of the spinal cord led not only to a structure fit for cartesian signalling molecules, but also to one with high processing power in which circuits for effecting movement syllables formed. These syllables are harnessed by higher regions of nervous systems to produce the complex movements required for interactions with others and with the surrounding environment.