To examine associations between sociodemographic and mental health characteristics with household risk for food insecurity during the COVID-19 outbreak.
Cross-sectional online survey analysed using ...univariable tests and a multivariable logistic regression model.
The United States during the week of 30 March 2020.
A convenience sample of 1965 American adults using Amazon's Mechanical Turk platform. Participants reporting household food insecurity prior to the pandemic were excluded from analyses.
One thousand two hundred and fifty participants reported household food security before the COVID-19 outbreak. Among this subset, 41 % were identified as at risk for food insecurity after COVID-19, 55 % were women and 73 % were white. On a multivariable analysis, race, income, relationship status, living situation, anxiety and depression were significantly associated with an incident risk for food insecurity. Black, Asian and Hispanic/Latino respondents, respondents with an annual income <$100 000 and those living with children or others were significantly more likely to be newly at risk for food insecurity. Individuals at risk for food insecurity were 2·60 (95 % CI 1·91, 3·55) times more likely to screen positively for anxiety and 1·71 (95 % CI 1·21, 2·42) times more likely to screen positively for depression.
An increased risk for food insecurity during the COVID-19 pandemic is common, and certain populations are particularly vulnerable. There are strong associations between being at risk for food insecurity and anxiety/depression. Interventions to increase access to healthful foods, especially among minority and low-income individuals, and ease the socioemotional effects of the outbreak are crucial to relieving the economic stress of this pandemic.
Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after ...injury
, but efficient reversal of this regrowth failure remains elusive
. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults-(i) neuron intrinsic growth capacity
, (ii) growth-supportive substrate
and (iii) chemoattraction
-are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. We reactivated the growth capacity of mature descending propriospinal neurons with osteopontin, insulin-like growth factor 1 and ciliary-derived neurotrophic factor before SCI
; induced growth-supportive substrates with fibroblast growth factor 2 and epidermal growth factor; and chemoattracted propriospinal axons with glial-derived neurotrophic factor
delivered via spatially and temporally controlled release from biomaterial depots
, placed sequentially after SCI. We show in both mice and rats that providing these three mechanisms in combination, but not individually, stimulated robust propriospinal axon regrowth through astrocyte scar borders and across lesion cores of non-neural tissue that was over 100-fold greater than controls. Stimulated, supported and chemoattracted propriospinal axons regrew a full spinal segment beyond lesion centres, passed well into spared neural tissue, formed terminal-like contacts exhibiting synaptic markers and conveyed a significant return of electrophysiological conduction capacity across lesions. Thus, overcoming the failure of axon regrowth across anatomically complete SCI lesions after maturity required the combined sequential reinstatement of several developmentally essential mechanisms that facilitate axon growth. These findings identify a mechanism-based biological repair strategy for complete SCI lesions that could be suitable to use with rehabilitation models designed to augment the functional recovery of remodelling circuits.
Astrocytes respond to injury and disease in the central nervous system with reactive changes that influence the outcome of the disorder
. These changes include differentially expressed genes (DEGs) ...whose contextual diversity and regulation are poorly understood. Here we combined biological and informatic analyses, including RNA sequencing, protein detection, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and conditional gene deletion, to predict transcriptional regulators that differentially control more than 12,000 DEGs that are potentially associated with astrocyte reactivity across diverse central nervous system disorders in mice and humans. DEGs associated with astrocyte reactivity exhibited pronounced heterogeneity across disorders. Transcriptional regulators also exhibited disorder-specific differences, but a core group of 61 transcriptional regulators was identified as common across multiple disorders in both species. We show experimentally that DEG diversity is determined by combinatorial, context-specific interactions between transcriptional regulators. Notably, the same reactivity transcriptional regulators can regulate markedly different DEG cohorts in different disorders; changes in the access of transcriptional regulators to DNA-binding motifs differ markedly across disorders; and DEG changes can crucially require multiple reactivity transcriptional regulators. We show that, by modulating reactivity, transcriptional regulators can substantially alter disorder outcome, implicating them as therapeutic targets. We provide searchable resources of disorder-related reactive astrocyte DEGs and their predicted transcriptional regulators. Our findings show that transcriptional changes associated with astrocyte reactivity are highly heterogeneous and are customized from vast numbers of potential DEGs through context-specific combinatorial transcriptional-regulator interactions.
•Resilience after a challenge occurs via neurobiological adaptations which allow normal brain function and behavior.•Mechanisms of resilience are distinct from mechanisms of vulnerability; protective ...factors are separate from risk factors.•Investigations of resilient animals to identify differences in gene expression and neuronal activity from susceptible or drug-naïve animals will likely identify novel addiction treatment targets.
The study of addiction has historically focused on identifying the differences which make susceptible individuals fall prey to drug use and abuse. This has resulted in a deep understanding of the learning, reward, and habit-formation circuits which drive initial drug reinforcement, as well as exploration of the cognitive control and anxiety systems which are important for craving and relapse to drug use. However, most human drug users and a smaller proportion of laboratory animals are resilient to addiction, meaning that they can use addictive drugs without developing substance use disorders. Evidence from the neurobiology of resilience in stress models suggests that the mechanisms of resilience are distinct from those of vulnerability, and thus may be missed if resilience is not investigated in a targeted manner. In this review, we briefly review the limitations in our knowledge which have resulted from a focus on addiction vulnerability. We next introduce the formal construct of resilience and its historical application in neurobiology and clinical research. Finally, we present evidence for the presence of resilience mechanisms in studies of addiction neuroscience and argue for an increase in the focused study of resilience to substance abuse. By intentionally identifying compensatory resilience mechanisms in addiction, rather than only focusing on mechanisms of susceptibility, more effective therapeutic approaches may be discovered.
COVID-19 has affected the health and well-being of almost every American. The aim of this study was to examine the sustained impacts of COVID-19 prevention measures on the diet and exercise habits, ...risk for food insecurity, and quality of life among adults in the U.S. We conducted a longitudinal study using a convenience sample of participants recruited via Amazon's Mechanical Turk (MTurk) platform between March 30 and April 7, 2020, and 8 months into the outbreak, from November 2 to November 21, 2020. We compared self-reported diet and exercise habits and risk for food insecurity shortly after the pandemic began, in April, to those reported in November. We also measured changes in quality-of-life using the PROMIS-29 + 2 (PROPr) scale. A total of 636 respondents completed both surveys. Compared to reports in April, respondents ate lunch and dinner out more frequently in November and consumed more take-out and fast food. Weekly frequencies of consuming frozen food and the number of daily meals were slightly lower in November than they were in April. 54% of respondents screened positively for being at risk for food insecurity in April, reducing to 41% by November. In April, survey respondents were found to have lower quality-of-life relative to U.S. population norms, but by November levels of depression and cognitive function had improved. Our findings underscore how the initial effects of the pandemic on diet, exercise, risk for food insecurity, and quality of life have evolved. As U.S. states re-open, continued efforts to encourage healthy eating and support mental health, especially to reduce feelings of anxiety and social isolation, remain important to mitigate the potential long-term effects of the pandemic.
Capicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic's function in the brain. We show that nuclear Cic ...expression is strongest in astrocytes and neurons but weaker in stem cells and oligodendroglial lineage cells. Using a new conditional Cic knockout mouse, we demonstrate that forebrain-specific Cic deletion increases proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage effects are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal, and tumorigenicity. Our results identify Cic as an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.
Background
Colon cancer incidence is rising in low‐ and middle‐income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the ...cost‐effectiveness of adjuvant chemotherapy for high‐risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC.
Methods
We created a decision‐analytic Markov model to compare lifetime costs and outcomes for patients with high‐risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost‐effectiveness ratio (ICER) in international dollars (I$) per disability‐adjusted life‐year (DALY) averted, at a willingness‐to‐pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted).
Results
CAPOX for 3 months was cost‐effective for both patients with high‐risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high‐risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost‐effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost‐effective cancer treatment strategies in resource‐constrained settings.
Conclusion
Colon cancer incidence is increasing in low‐ and middle‐income countries, including South Africa, where resource constraints can impact treatment decisions. This cost‐effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high‐risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost‐effective strategy and should be recommended in South Africa.
Colon cancer incidence is increasing in low‐ and middle‐income countries, including South Africa, where resource constraints can impact treatment decisions. This cost‐effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high‐risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost‐effective strategy and should be recommended in South Africa.
Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here ...we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.
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•Unbiased RABV screen identifies drug-induced changes in rodent brain•BNSTGABA→midbrain cell activity is elevated after a single cocaine exposure•BNSTGABA→VTADA→amygdala pathway controls cocaine-induced anxiety and reinstatement•VTADA→amygdala cells are necessary and sufficient to drive general anxiety states
Tian et al. show that an elevation of BNSTGABA→midbrain cell activity is related to withdrawal anxiety that manifests after a single cocaine exposure. Inhibition or activation of the BNSTGABA→VTADA→amygdala pathway bidirectionally controls cocaine-induced withdrawal anxiety. Activation of VTADA→amygdala cells is also sufficient to drive robust reinstatement of cocaine-induced place preference.
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