Cell Therapies for Acute Radiation Syndrome.

The risks of severe ionizing radiation exposure are increasing due to the involvement of nuclear powers in combat operations, the increasing use of nuclear power, and the existence of terrorist threats. Exposure to a whole-body radiation dose above about 0.7 Gy results in H-ARS (hematopoietic acute radiation syndrome), which is characterized by damage to the hematopoietic system; higher doses result in further damage to the gastrointestinal and nervous systems. Only a few medical countermeasures for ARS are currently available and approved for use, although others are in development. Cell therapies (cells or products produced by cells) are complex therapeutics that show promise for the treatment of radiation injury and have been shown to reduce mortality and morbidity in animal models. Since clinical trials for ARS cannot be ethically conducted, animal testing is extremely important. Here, we describe cell therapies that have been tested in animal models. Both cells and cell products appear to promote survival and lessen tissue damage after whole-body irradiation, although the mechanisms are not clear. Because radiation exposure often occurs in conjunction with other traumatic injuries, animal models of combined injury involving radiation and future countermeasure testing for these complex medical problems are also discussed.

The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation.

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomics resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomics resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, anti- predator strategies, and resilience and adaptive responses. They also serve as critical models for understanding widespread genomic characteristics, including evolutionary genome expansions and contractions given they have the largest range in genome sizes of any animal taxon and multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The advent of long-read sequencing technologies, along with computational techniques that enhance scaffolding capabilities and streamline computational workload is now enabling the ability to overcome some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC) in early 2023. This burgeoning community already has more than 282 members from 41 countries (6 in Africa, 131 in the Americas, 27 in Asia, 29 in Australasia, and 89 in Europe). The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and outline how the AGC can enable amphibian genomics research to "leap" to the next level.

Improving processing speed in adolescents at clinical high risk for psychosis with the Specific COgnitive REmediation plus Surround (SCORES) intervention: Study protocol.

AIM: Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old. METHODS: In the first R61 phase, a single-arm 2-year proof of concept study, 30 CHR-P individuals will receive SCORES for 10 weeks (4 h per week/40 h total) with a midpoint assessment at 20 h (5 weeks) to demonstrate target engagement and identify the optimal dose needed to engage the target. The Go/No-Go criteria to move to the R33 phase will be processing speed scores improving by a medium effect size (Cohen's d ≥ .6). The proposed package includes a set of complimentary support surround procedures to increase enjoyment and ensure that participants will complete the home-based training. In the second R33 phase, a 3-year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR-P individuals randomized to SCORES (optimized dose) or to a video game playing control condition. In addition, the R33 phase will determine if changes in processing speed are associated with improved social functioning and decreasing attenuated positive symptoms. The support surround components of the intervention will remain constant across phases and conditions in the R33 phase to firmly establish the centrality of processing speed training for successful remediation. CONCLUSIONS: The SCORES study is a completely virtual intervention that targets a core cognitive mechanism, processing speed, which is a rate-limiting factor to higher order behaviours and clinical outcomes in CHR-P adolescents. The virtual nature of this study should increase feasibility as well improve the future scalability of the intervention with considerable potential for future dissemination as a complete treatment package.

Comparison of approach/avoidance intentions for alcohol and vegetable consumption under a temporal self-regulation theory framework.

OBJECTIVE: This study aimed to compare the differences between the framing of intention (approach vs. avoidance) and the type of self-regulatory capacity (planning vs. inhibition) to predict two behaviours (alcohol vs. vegetable consumption). Interaction effects between temporal self-regulation theory constructs were also explored. METHODS: UK participants were recruited online (N = 254) and completed measures of intention (approach and avoidance), self-regulatory capacity (planning and inhibition), and behavioural prepotency (habit) related to alcohol and vegetable consumption. One week later, consumption was assessed. RESULTS: Habit strength and approach-intentions consistently predicted consumption across each model for both behaviours. There was mixed support for avoidance-intentions and self-regulatory capacity variables in predicting consumption. Planning was more important in vegetable consumption than in alcohol consumption, and avoidance-intentions were only predictive in alcohol consumption. Inhibition was not significant for either behaviour. The interaction between approach-intention and planning was the only significant moderation detected and was only present in vegetable consumption. CONCLUSION: The framing of intentions and the sub-facet of self-regulatory capacity are important to consider when attempting to explain health behaviours. Furthermore, theoretically defined moderation between temporal self-regulation theory variables might also depend on the type of behaviour and specific measured used to capture self-regulatory capacity.

Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

PURPOSE: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring EGFR mutations. METHODS: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS). RESULTS: Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities. CONCLUSION: Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial's primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.

Critical Review of Field Studies of Chemical Surface Coatings to Mitigate Leaching from Mining Wastes.

Source control of mine drainage and leachate from mining wastes is ideal, but there is limited use of control methods aside from removal of wastes to repositories or capping wastes in situ. In some locations, neither removal nor capping is possible; thus, there is renewed interest in understanding technologies for coating mining wastes. This paper presents the current state of knowledge from a critical review of the few field case studies where chemical coating technologies have been applied to mined surfaces (e.g. a highwall) or mining wastes. It also includes laboratory studies where the same technology was examined on the same type of waste material as the field studies. The chemicals used in field studies for coating mining wastes were magnesium oxide, potassium permanganate, silicate compounds, phosphate compounds, and a furfuryl alcohol resin sealant. Descriptions of the methods employed, and results obtained are provided. Limitations of the individual studies and of the technologies in general are discussed. Potential reasons why coating technologies have not been commonly used are presented, along with further research needs.

Case of a CIC::DUX4 fusion gene in a vascular neoplasm extends the spectrum of CIC-rearranged sarcomas.

CIC-rearranged sarcomas comprise a group of exceptionally aggressive round-cell sarcomas. These tumors most commonly demonstrate CIC::DUX4 fusion and show similar histopathology to Ewing sarcomas, though lesions mimicking vascular neoplasms have recently been described. Here, we describe a case of a patient with CIC::DUX4 fusion sarcoma identified using RNA-based molecular testing who was initially diagnosed with an endothelial neoplasm. The tumor showed extensive vasoformative growth, complete WT1 negativity, and global positive staining for ERG, CD31, and DUX4 by immunohistochemistry. Methylation testing of the tumor clustered more closely with angiosarcomas than with CIC-rearranged sarcomas. Our findings suggest that CIC::DUX4 fused neoplasms may demonstrate a more diverse phenotypic range than previously appreciated and offer evidence that both molecular and immunohistochemical studies are needed for accurate diagnosis.

Mexican-origin women's individual and collective strategies to access and share health-promoting resources in the context of exclusionary immigration and immigrant policies.

BACKGROUND: A growing literature has documented the social, economic, and health impacts of exclusionary immigration and immigrant policies in the early 21st century for Latiné communities in the US, pointing to immigration and immigrant policies as forms of structural racism that affect individual, family, and community health and well-being. Furthermore, the past decade has seen an increase in bi-partisan exclusionary immigration and immigrant policies. Immigration enforcement has been a major topic during the 2024 Presidential election cycle, portending an augmentation of exclusionary policies towards immigrants. Within this context, scholars have called for research that highlights the ways in which Latiné communities navigate exclusionary immigration and immigrant policies, and implications for health. This study examines ways in which Mexican-origin women in a midwestern northern border community navigate restrictive immigration and immigrant policies to access health-promoting resources and care for their well-being. METHODS: We conducted a grounded theory analysis drawing on interviews with 48 Mexican-origin women in Detroit, Michigan, who identified as being in the first, 1.5, or second immigrant generation. Interviews were conducted in English or Spanish, depending on participants' preferences, and were conducted at community-based organizations or other locations convenient to participants in 2013-2014. RESULTS: Women reported encountering an interconnected web of institutional processes that used racializing markers to infer legal status and eligibility to access health-promoting resources. Our findings highlight women's use of both individual and collective action to navigate exclusionary policies and processes, working to: (1) maintain access to health-promoting resources; (2) limit labeling and stigmatization; and (3) mitigate adverse impacts of immigrant policing on health and well-being. The strategies women engaged were shaped by both the immigration processes and structures they confronted, and the resources to which they had access to within their social network. CONCLUSIONS: Our findings suggest a complex interplay of immigration-related policies and processes, social networks, and health-relevant resources. They highlight the importance of inclusive policies to promote health for immigrant communities. These findings illuminate women's agency in the context of structural violence facing immigrant women and are particularly salient in the face of anti-immigrant rhetoric and exclusionary immigration and immigrant policies.

Development of desmoid tumours after ileorectal anastomosis versus ileal pouch-anal anastomosis in familial adenomatous polyposis.

BACKGROUND & AIMS: Desmoid tumours (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: We performed an international historical cohort study in FAP patients who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS: We analysed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The post-operative risk was significantly higher after IPAA (p < 0.01) in multivariable analysis, while approach did not significantly influence the risk. CONCLUSIONS: The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

Functional neurological disorder, physical activity and exercise: What we know and what we can learn from comorbid disorders.

Functional neurological disorder (FND) is a common neurologic disorder associated with many comorbid symptoms including fatigue, pain, headache, and orthostasis. These concurrent symptoms lead patients to accumulate multiple diagnoses comorbid with FND, including fibromyalgia, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, persistent post-concussive symptoms, and chronic pain. The role of physical activity and exercise has not been evaluated in FND populations, though has been studied in certain comorbid conditions. In this traditional narrative literature review, we highlight some existing literature on physical activity in FND, then look to comorbid disorders to highlight the therapeutic potential of physical activity. We then consider abnormalities in the autonomic nervous system (ANS) as a potential pathophysiological explanation for symptoms in FND and comorbid disorders and postulate how physical activity and exercise may provide benefit via autonomic regulation.

Ampicillin-Sulbactam for Carbapenem-Susceptible Acinetobacter baumannii Pneumonia: A Case for High-Dose, Continuous Infusion Dosing Strategy in the Trauma ICU.

Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. Output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets (PNNs). We previously showed that ABC treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference (CPP) memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Further, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.Significance Statement Powerful memories are associated with drug-taking behavior over extended periods, and these memories can drive relapse to drugs of abuse. The medial prefrontal cortex (mPFC) is a major contributor to relapse in cocaine use disorder. In a well-established rodent model of cocaine use disorder, we identify how removal of key extracellular matrix structures called perineuronal nets (PNNs) within the mPFC reduces the ability to update a cocaine memory. We further show that the ABC treatment within the mPFC impairs the coupling of oscillations between the mPFC and dorsal hippocampus during the updating of cocaine memory. This impaired communication between mPFC and hippocampal circuitry may act as a signature for disrupting cocaine-related memories to help break the cycle of relapse.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Correlates of Adherence to Oral and Vaginal Pre-exposure Prophylaxis (PrEP) Among Adolescent Girls and Young Women (AGYW) Participating in the MTN-034/REACH Trial.

We evaluated correlates of adherence to PrEP, including daily oral tenofovir disoproxil fumarate in combination emtricitabine (oral FTC/TDF) and the monthly dapivirine ring (ring)among adolescent girls and young women (AGYW) in the MTN-034/REACH study. We enrolled 247 AGYW aged 16-21 years in South Africa, Uganda and Zimbabwe (ClinicalTrials.gov: NCT03074786). Participants were randomized to the order of oral FTC/TDF or ring use for 6 months each in a crossover period, followed by a 6-month choice period. We assessed potential adherence correlates-individual, interpersonal, community, study, and product-related factors-quarterly via self-report. We measured biomarkers of adherence monthly; high adherence was defined as > 4 mg dapivirine released from returned rings or intracellular tenofovir diphosphate levels ≥ 700 fmol/punch from dried blood spots (DBS). We tested associations between correlates and objective measures of high adherence using generalized estimating equations. High adherence to oral FTC/TDF was significantly associated with having an older primary partner (p = 0.04), not having exchanged sex in the past 3 months (p = 0.02), and rating oral FTC/TDF as highly acceptable (p = 0.003). High ring adherence was significantly associated with unstable housing (p = 0.01), disclosing ring use to a male family member (p = 0.01), and noting a social benefit from study participation (p = 0.03). All associations were moderate, corresponding to about 6%-10% difference in the proportion with high adherence. In our multinational study, correlates of adherence among African AGYW differed for oral FTC/TDF and the ring, highlighting the benefit of offering multiple PrEP options.

A joint ESTRO and AAPM guideline for development, clinical validation and reporting of artificial intelligence models in radiation therapy.

BACKGROUND AND PURPOSE: Artificial Intelligence (AI) models in radiation therapy are being developed with increasing pace. Despite this, the radiation therapy community has not widely adopted these models in clinical practice. A cohesive guideline on how to develop, report and clinically validate AI algorithms might help bridge this gap. METHODS AND MATERIALS: A Delphi process with all co-authors was followed to determine which topics should be addressed in this comprehensive guideline. Separate sections of the guideline, including Statements, were written by subgroups of the authors and discussed with the whole group at several meetings. Statements were formulated and scored as highly recommended or recommended. RESULTS: The following topics were found most relevant: Decision making, image analysis, volume segmentation, treatment planning, patient specific quality assurance of treatment delivery, adaptive treatment, outcome prediction, training, validation and testing of AI model parameters, model availability for others to verify, model quality assurance/updates and upgrades, ethics. Key references were given together with an outlook on current hurdles and possibilities to overcome these. 19 Statements were formulated. CONCLUSION: A cohesive guideline has been written which addresses main topics regarding AI in radiation therapy. It will help to guide development, as well as transparent and consistent reporting and validation of new AI tools and facilitate adoption.

Strong versus Weak Data Labeling for Artificial Intelligence Algorithms in the Measurement of Geographic Atrophy.

Purpose: To gain an understanding of data labeling requirements to train deep learning models for measurement of geographic atrophy (GA) with fundus autofluorescence (FAF) images. Design: Evaluation of artificial intelligence (AI) algorithms. Subjects: The Age-Related Eye Disease Study 2 (AREDS2) images were used for training and cross-validation, and GA clinical trial images were used for testing. Methods: Training data consisted of 2 sets of FAF images; 1 with area measurements only and no indication of GA location (Weakly labeled) and the second with GA segmentation masks (Strongly labeled). Main Outcome Measures: Bland-Altman plots and scatter plots were used to compare GA area measurement between ground truth and AI measurements. The Dice coefficient was used to compare accuracy of segmentation of the Strong model. Results: In the cross-validation AREDS2 data set (n = 601), the mean (standard deviation [SD]) area of GA measured by human grader, Weakly labeled AI model, and Strongly labeled AI model was 6.65 (6.3) mm2, 6.83 (6.29) mm2, and 6.58 (6.24) mm2, respectively. The mean difference between ground truth and AI was 0.18 mm2 (95% confidence interval, [CI], -7.57 to 7.92) for the Weakly labeled model and -0.07 mm2 (95% CI, -1.61 to 1.47) for the Strongly labeled model. With GlaxoSmithKline testing data (n = 156), the mean (SD) GA area was 9.79 (5.6) mm2, 8.82 (4.61) mm2, and 9.55 (5.66) mm2 for human grader, Strongly labeled AI model, and Weakly labeled AI model, respectively. The mean difference between ground truth and AI for the 2 models was -0.97 mm2 (95% CI, -4.36 to 2.41) and -0.24 mm2 (95% CI, -4.98 to 4.49), respectively. The Dice coefficient was 0.99 for intergrader agreement, 0.89 for the cross-validation data, and 0.92 for the testing data. Conclusions: Deep learning models can achieve reasonable accuracy even with Weakly labeled data. Training methods that integrate large volumes of Weakly labeled images with small number of Strongly labeled images offer a promising solution to overcome the burden of cost and time for data labeling. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cannabis and vaping nicotine: An exploration of risk factors using a nationally representative sample of youth and young adults.

BACKGROUND: Given that cannabis and e-cigarettes are among the most commonly used substances among young people, there is a need to identify risk factors for concurrent cannabis consumption and nicotine vaping among youth and young adults. METHODS: Data were obtained from the Truth Longitudinal Cohort, collected from September 2020 to March 2021, among a cohort aged 15-24 years (N = 6379). Chi-square tests were conducted to detect differences in sample characteristics by dual use status (never e-cigarette and never cannabis users, never cannabis and former/noncurrent e-cigarette users, never e-cigarette and former/noncurrent cannabis users, former/noncurrent e-cigarette and cannabis users, current e-cigarette only users, current cannabis only users, and concurrent cannabis and e-cigarette dual users). Multinomial logistic regression was used to determine key demographic variables predicting dual use status. RESULTS: Household tobacco use (Relative Risk Ratio, RRR = 4.93), higher sensation seeking (RRR = 3.98), and mental health score (RRR = 2.58) were associated with higher risk of dual use. Being 15-17 years (RRR = 0.22), being female (RRR = 0.59) and having parents with an education level of some college or more (RRR = 0.64) were associated with lower risk of dual use. CONCLUSION: Findings suggest the need to carefully monitor cannabis and vaping nicotine among young people. The identification of risk factors provides additional guidance for prevention and treatment efforts, suggesting the need to address use of both substances and target those most at risk.

A Systematic Review of Extracellular Matrix-Related Alterations in Parkinson's Disease.

The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This systematic review identified the top deregulated ECM-related pathways in studies that used gene set enrichment analyses (GSEA) to document transcriptomic, proteomic, or genomic alterations in PD. PubMed and Google scholar were searched for transcriptomics, proteomics, or genomics studies that employed GSEA on data from PD tissues or cells and reported ECM-related pathways among the top-10 most enriched versus controls. Twenty-seven studies were included, two of which used multiple omics analyses. Transcriptomics and proteomics studies were conducted on a variety of tissue and cell types. Of the 17 transcriptomics studies (16 data sets), 13 identified one or more adhesion pathways in the top-10 deregulated gene sets or pathways, primarily related to cell adhesion and focal adhesion. Among the 8 proteomics studies, 5 identified altered overarching ECM gene sets or pathways among the top 10. Among the 4 genomics studies, 3 identified focal adhesion pathways among the top 10. The findings summarized here suggest that ECM organization/structure and cell adhesion (particularly focal adhesion) are altered in PD and should be the focus of future studies.

Toxoplasma gondii chitinase-like protein TgCLP1 regulates the parasite cyst burden.

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Although Toxoplasma secretory proteins during acute infection (tachyzoite, which divides rapidly and causes inflammation) have been extensively characterized, those involved in chronic infection (bradyzoite, which divides slowly and is surrounded by a cyst wall) remain uncertain. Regulation of the cyst wall is essential to the parasite life cycle, and polysaccharides, such as chitin, in the cyst wall are necessary to sustain latent infection. Toxoplasma secretory proteins during the bradyzoite stage may have important roles in regulating the cyst wall via polysaccharides. Here, we focused on characterizing the hypothetical T. gondii chitinase, chitinase-like protein 1 (TgCLP1). We found that the chitinase-like domain containing TgCLP1 is partially present in the bradyzoite microneme and confirmed, albeit partially, its previous identification in the tachyzoite microneme. Furthermore, although parasites lacking TgCLP1 could convert from tachyzoites to bradyzoites and make an intact cyst wall, they failed to convert from bradyzoites to tachyzoites, indicating that TgCLP1 is necessary for bradyzoite reactivation. Taken together, our findings deepen our understanding of the molecular basis of recrudescence and could contribute to the development of novel strategies for the control of toxoplasmosis.