The myth of the urban peasant

This paper explores, the ‘myth of the urban peasant’, the widespread belief that urban Russian households are surviving the collapse of employment and money incomes by turning to subsistence agriculture. On the basis of the analysis of official and survey data the paper shows that although many urban households grow food in their garden plots, those with low money incomes are the least likely to do so, while subsistence production is a complement rather than an alternative to paid employment. Moreover, those who do grow their own food work long hours for very little return, spending no less of their money income on buying food than do those who grow nothing. The implication is that dacha use is a leisure activity of the better-off rather than a survival strategy of the poor. Regional data suggests that urban agricultural production persists in those regions in which commercial agriculture and monetised relations are least developed which, it is surmised, retain memories of past shortages

Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

Objective: To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. Design: Systematic review and meta-analysis. Data sources: Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts. Data synthesis and study quality: Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges’ g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies’ sample sizes. Study quality was appraised using Cochrane’s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines. Eligibility criteria: Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible. Results: Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges’ g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges’ g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating. Conclusion: Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant. Systematic review registration: PROSPERO CRD42023388065

Community health workers in South Africa: Where in this maze do we find ourselves?

Background The increasing burden on health services of HIV/AIDS and tuberculosis, as well as the need to meet the Millennium Development Goals for health, has renewed interest in community health worker (CHW) programmes in South Africa. The recent Expanded Public Works Social Sector Plan promotes CHW programmes as a mechanism for addressing the health, social, educational and employment needs of disadvantaged communities. This paper reports key issues emerging from a two day workshop for health policy-makers, project managers and researchers, on the implementation of CHW projects. Results The workshop considered a wide range of issues. Robust evidence for the effectiveness of focused CHW interventions, where this cadre function within a limited scope of practice, is now available but further evidence on the effects of ‘generalist’ CHWs is necessary before wide roll-out can be recommended. Further work is also needed on approaches to evaluating CHW programmes, given their complexity and the need to understand the impacts of context. How best to organize CHW programmes, including community participation and approaches to training, were debated. Several key challenges facing CHW programmes in South Africa were identified, including responsiveness to community needs; financing; training; programme management and CHW supervision. Further research on the cost-effectiveness of CHW interventions and on factors affecting scaling up of programmes is required. Conclusions Although a national CHW policy framework is now in place in South Africa, many questions and challenges related to implementation remain. The renewed interest in CHW programmes provides opportunities to examine these questions and to increase the contribution of CHWs to improving health in South Africa

Interdisciplinary Approach to Improve Access to Medication-Assisted Therapy in Detroit for Opioid Dependence

Medical Schoolhttps://deepblue.lib.umich.edu/bitstream/2027.42/149416/1/MarinaHaque_1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149416/2/MarinaHaque_2.pd

Long Non-coding RNAs Are Central Regulators of the IL-1β-Induced Inflammatory Response in Normal and Idiopathic Pulmonary Lung Fibroblasts

There is accumulating evidence to indicate that long non-coding RNAs (lncRNAs) are important regulators of the inflammatory response. In this report, we have employed next generation sequencing to identify 14 lncRNAs that are differentially expressed in human lung fibroblasts following the induction of inflammation using interleukin-1β (IL-1β). Knockdown of the two most highly expressed lncRNAs, IL7AS, and MIR3142HG, showed that IL7AS negatively regulated IL-6 release whilst MIR3142HG was a positive regulator of IL-8 and CCL2 release. Parallel studies in fibroblasts derived from patients with idiopathic pulmonary fibrosis showed similar increases in IL7AS levels, that also negatively regulate IL-6 release. In contrast, IL-1β-induced MIR3142HG expression, and its metabolism to miR-146a, was reduced by 4- and 9-fold in IPF fibroblasts, respectively. This correlated with a reduced expression of inflammatory mediators whilst MIR3142HG knockdown showed no effect upon IL-8 and CCL2 release. Pharmacological studies showed that IL-1β-induced IL7AS and MIR3142HG production and release of IL-6, IL-8, and CCL2 in both control and IPF fibroblasts were mediated via an NF-κB-mediated pathway. In summary, we have cataloged those lncRNAs that are differentially expressed following IL-1β-activation of human lung fibroblasts, shown that IL7AS and MIR3142HG regulate the inflammatory response and demonstrated that the reduced inflammatory response in IPF fibroblast is correlated with attenuated expression of MIR3142HG/miR-146a

Bulge-Forming miRNases Cleave Oncogenic miRNAs at the Central Loop Region in a Sequence-Specific Manner.

The selective degradation of disease-associated microRNA is promising for the development of new therapeutic approaches. In this study, we engineered a series of bulge-loop-forming oligonucleotides conjugated with catalytic peptide [(LeuArg)(2)Gly](2) (BC–miRNases) capable of recognizing and destroying oncogenic miR-17 and miR-21. The principle behind the design of BC–miRNase is the cleavage of miRNA at a three-nucleotide bulge loop that forms in the central loop region, which is essential for the biological competence of miRNA. A thorough study of mono- and bis-BC–miRNases (containing one or two catalytic peptides, respectively) revealed that: (i) the sequence of miRNA bulge loops and neighbouring motifs are of fundamental importance for efficient miRNA cleavage (i.e., motifs containing repeating pyrimidine–A bonds are more susceptible to cleavage); (ii) the incorporation of the second catalytic peptide in the same molecular scaffold increases the potency of BC–miRNase, providing a complete degradation of miR-17 within 72 h; (iii) the synergetic co-operation of BC–miRNases with RNase H accelerates the rate of miRNA catalytic cleavage by both the conjugate and the enzyme. Such synergy allows the rapid destruction of constantly emerging miRNA to maintain sufficient knockdown and achieve a desired therapeutic effect

Engineering supramolecular dynamics of self-assembly and turnover of oncogenic microRNAs to drive their synergistic destruction in tumor models

Rationally-engineered functional biomaterials offer the opportunity to interface with complex biology in a predictive, precise, yet dynamic way to reprogram their behaviour and correct shortcomings. Success here may lead to a desired therapeutic effect against life-threatening diseases, such as cancer. Here, we engineered “Crab”-like artificial ribonucleases through coupling of peptide and nucleic acid building blocks, capable of operating alongside and synergistically with intracellular enzymes (RNase H and Ago 2) for potent destruction of oncogenic microRNAs. “Crab”-like configuration of two catalytic peptides (“pincers”) flanking the recognition oligonucleotide was instrumental here in providing increased catalytic turnover, leading to ≈30-fold decrease in miRNA half-life as compared with that for “single-pincer” conjugates. Dynamic modelling of miRNA cleavage illustrated how such design enabled “Crabs” to drive catalytic turnover through simultaneous attacks at different locations of the RNA-DNA heteroduplex, presumably by producing smaller cleavage products and by providing toeholds for competitive displacement by intact miRNA strands. miRNA cleavage at the 5’-site, spreading further into double-stranded region, likely provided a synergy for RNase H1 through demolition of its loading region, thus facilitating enzyme turnover. Such synergy was critical for sustaining persistent disposal of continually-emerging oncogenic miRNAs. A single exposure to the best structural variant (Crab-p-21) prior to transplantation into mice suppressed their malignant properties and reduced primary tumor volume (by 85%) in MCF-7 murine xenograft models

Understanding profound autism: implications for stigma and supports

IntroductionSocietal perceptions and lack of understanding of autism spectrum disorder can be stigmatizing for autistic individuals and their families. This may be particularly the case for individuals who meet criteria for profound autism. Despite the considerable service needs of this marginalized group, there is little data on the prevalence of profound autism, nor on the experiences of those with profound autism and their families.MethodsThe current study leveraged a mixed-methods approach to address these gaps. First, the prevalence of profound autism was examined in six samples—three from the United States and three from Western Europe. Second, inductive thematic analysis was used to code interviews from 20 caregivers of profoundly autistic adults.ResultsThe prevalence of profound autism varied widely across the six samples—from 11% to 48%. There were also notable differences between samples in prevalence by gender, race, and ethnicity. Two overarching themes were identified via inductive thematic analysis: Community Perceptions of Autism and Family Support Needs and Advocacy Challenges. Though caregivers were not directly asked about stigmatization during interviews, 85% of caregivers reported at least one instance of perceived stigma.DiscussionFuture research should continue to examine the unique needs and stigmatization experiences of profoundly autistic individuals and their families across the life course

Neural Network Based Uncertainty Prediction for Autonomous Vehicle Application

This paper proposes a framework for uncertainty prediction in complex fusion networks, where signals become available sporadically. Assuming there is no information of the sensor characteristics available, a surrogated model of the sensor uncertainty is yielded directly from data through artificial neural networks. The strategy developed is applied to autonomous vehicle localization through odometry sensors (speed and orientation), so as to determine the location uncertainty in the trajectory. The results obtained allow for fusion of autonomous vehicle location measurements, and effective correction of the accumulated odometry error in most scenarios. The neural networks applicability and generalization capacity are proven, evidencing the suitability of the presented methodology for uncertainty estimation in non-linear and intractable processes