Despite its cultivation as a source of food, fibre and medicine, and its global status as the most used illicit drug, the genus Cannabis has an inconclusive taxonomic organization and evolutionary ...history. Drug types of Cannabis (marijuana), which contain high amounts of the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC), are used for medical purposes and as a recreational drug. Hemp types are grown for the production of seed and fibre, and contain low amounts of THC. Two species or gene pools (C. sativa and C. indica) are widely used in describing the pedigree or appearance of cultivated Cannabis plants. Using 14,031 single-nucleotide polymorphisms (SNPs) genotyped in 81 marijuana and 43 hemp samples, we show that marijuana and hemp are significantly differentiated at a genome-wide level, demonstrating that the distinction between these populations is not limited to genes underlying THC production. We find a moderate correlation between the genetic structure of marijuana strains and their reported C. sativa and C. indica ancestry and show that marijuana strain names often do not reflect a meaningful genetic identity. We also provide evidence that hemp is genetically more similar to C. indica type marijuana than to C. sativa strains.
Child maltreatment is a global public health issue that encompasses physical abuse, sexual abuse, emotional abuse, neglect, and exposure to intimate partner violence (IPV). This systematic review and ...meta-analysis summarises the association between these five forms of child maltreatment and depressive and anxiety disorders.
Published cohort and case-control studies were included if they reported associations between any form of child maltreatment (and/or a combination of), and depressive and anxiety disorders. A total of 604 studies were assessed for eligibility, 106 met inclusion criteria, and 96 were included in meta-analyses. The data were pooled in random effects meta-analyses, giving odds ratios (ORs) with corresponding 95% confidence intervals (CIs) for each form of child maltreatment.
All forms of child maltreatment were associated with depressive disorders (any child maltreatment OR = 2.48, 2.14–2.87; sexual abuse OR = 2.11, 1.83–2.44; physical abuse OR = 1.78, 1.57–2.01; emotional abuse OR = 2.35, 1.74–3.18; neglect OR = 1.65, 1.35–2.02; and exposure to IPV OR = 1.68, 1.34–2.10). Several forms of child maltreatment were significantly associated with anxiety disorders (‘any child maltreatment’ OR = 1.68, 1.33–2.4; sexual abuse OR = 1.90, 1.6–2.25; physical abuse OR = 1.56, 1.39–1.76; and neglect OR = 1.34, 1.09–1.65). Significant associations were also found between several forms of child maltreatment and post-traumatic stress disorder (PTSD).
There is a robust association between five forms of child maltreatment and the development of mental disorders. The Global Burden of Disease Study (GBD) includes only sexual abuse as a risk factor for depressive and anxiety disorders. These findings support the inclusion of additional forms of child maltreatment as risk factors in GBD.
For individuals with human immunodeficiency virus (HIV) infection to fully benefit from potent combination antiretroviral therapy, they need to know that they are HIV infected, be engaged in regular ...HIV care, and receive and adhere to effective antiretroviral therapy. Test-and-treat strategies for HIV prevention posit that expanded testing and earlier treatment of HIV infection could markedly decrease ongoing HIV transmission, stemming the HIV epidemic. However, poor engagement in care for HIV-infected individuals will substantially limit the effectiveness of test-and-treat strategies. We review the spectrum of engagement in care for HIV-infected individuals in the United States and apply this information to help understand the magnitude of the challenges that poor engagement in care will pose to test-and-treat strategies for HIV prevention.
Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We ...previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.
Abstract
Stormwater is a largely uncontrolled source of pollution in rural and urban environments across the United States. Concern regarding the growing diversity and abundance of pollutants in ...stormwater, as well as their impacts on water quality, has grown significantly over the past several decades. In addition to conventional contaminants like nutrients and heavy metals, stormwater is a well-documented source of many contaminants of emerging concern, which can be toxic to both aquatic and terrestrial organisms and remain a barrier to maintaining high quality water resources. Chemical pollutants like pharmaceuticals and personal care products, industrial pollutants such as per- and polyfluoroalkyl substances, and tire wear particles in stormwater are of great concern due to their toxic, genotoxic, mutagenic and carcinogenic properties. Emerging microbial contaminants such as pathogens and antibiotic resistance genes also represent significant threats to environmental water quality and human health. Knowledge regarding the transport, behavior, and the remediation capacity of these pollutants in runoff is key for addressing these pollutants in situ and minimizing ecosystem perturbations. To this end, this review paper will analyze current understanding of these contaminants in stormwater runoff in terms of their transport, behavior, and bioremediation potential.
Secretory and transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded proteins and exit as either folded proteins in transit to their target organelles or as misfolded proteins ...targeted for degradation. The unfolded protein response (UPR) maintains the protein-folding homeostasis within the ER, ensuring that the protein-folding capacity of the ER meets the load of client proteins. Activation of the UPR depends on three ER stress sensor proteins, Ire1, PERK, and ATF6. Although the consequences of activation are well understood, how these sensors detect ER stress remains unclear. Recent evidence suggests that yeast Ire1 directly binds to unfolded proteins, which induces its oligomerization and activation. BiP dissociation from Ire1 regulates this oligomeric equilibrium, ultimately modulating Ire1's sensitivity and duration of activation. The mechanistic principles of ER stress sensing are the focus of this review.
The pursuit of p-type semiconductors has garnered considerable attention in academia and industry. Among the potential candidates, copper iodide (CuI) stands out as a highly promising
-type material ...due to its conductivity, cost-effectiveness, and low environmental impact. CuI can be employed to create thin films with >80% transparency within the visible range (400-750 nm) and utilizing various low-temperature, scalable deposition techniques. This review summarizes the deposition techniques for CuI as a hole-transport material and their performance in perovskite solar cells, thin-film transistors, and light-emitting diodes using diverse processing methods. The preparation methods of making thin films are divided into two categories: wet and neat methods. The advancements in CuI as a hole-transporting material and interface engineering techniques hold promising implications for the continued development of such devices.
Disease epidemic outbreaks on human metapopulation networks are often driven by a small number of superspreader nodes, which are primarily responsible for spreading the disease throughout the ...network. Superspreader nodes typically are characterized either by their locations within the network, by their degree of connectivity and centrality, or by their habitat suitability for the disease, described by their reproduction number (R). Here we introduce a model that considers simultaneously the effects of network properties and R on superspreaders, as opposed to previous research which considered each factor separately. This type of model is applicable to diseases for which habitat suitability varies by climate or land cover, and for direct transmitted diseases for which population density and mitigation practices influences R. We present analytical models that quantify the superspreader capacity of a population node by two measures: probability-dependent superspreader capacity, the expected number of neighboring nodes to which the node in consideration will randomly spread the disease per epidemic generation, and time-dependent superspreader capacity, the rate at which the node spreads the disease to each of its neighbors. We validate our analytical models with a Monte Carlo analysis of repeated stochastic Susceptible-Infected-Recovered (SIR) simulations on randomly generated human population networks, and we use a random forest statistical model to relate superspreader risk to connectivity, R, centrality, clustering, and diffusion. We demonstrate that either degree of connectivity or R above a certain threshold are sufficient conditions for a node to have a moderate superspreader risk factor, but both are necessary for a node to have a high-risk factor. The statistical model presented in this article can be used to predict the location of superspreader events in future epidemics, and to predict the effectiveness of mitigation strategies that seek to reduce the value of R, alter host movements, or both.
Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV preexposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) ...in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, crossover pharmacokinetic study of TFV-DP in DBS during 33%, 67%, or 100% of daily dosing under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty-eight adults (25 women) from Denver and San Francisco were included. TFV-DP exhibited a median half-life of 17 days, reaching steady state in 8 weeks. TFV-DP was dose proportional with mean (SD) steady-state concentrations of 530 (159), 997 (267), and 1,605 (405) fmol/punch for the 33%, 67%, and 100% arms, respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP thresholds of 350, 700, and 1,250 fmol/punch, which were estimated 25th percentiles for 2, 4, and 7 doses/week. In the present study, corresponding TFV-DP was within 3% of the prior estimates, and subgroups by site, race, and sex were within 14% of prior estimates, although males had 17.6% (95% confidence intervals CIs, 6.5, 27.4%) lower TFV-DP than females. The thresholds of 350, 700, and 1,250 fmol/punch were achieved by 75% of men taking ≥1.2, 3.2, and 6 doses/week and 75% of women taking ≥0.6, 2.0, and 5.3 doses/week, indicating that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP arising from DOT was similar to previous estimates and is useful for interpreting PrEP adherence and study outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02022657.).
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