Notes

First complete mitochondrial genome regarding Rhodinia species (Lepidoptera: Saturniidae): genome information along with phylogenetic implication.
Metastatic thyroid cancers may dedifferentiate and become radioactive iodine refractory. The redifferentiating effect of pharmacological drugs was reported with inhibitors of the MAPK pathway in cancer with point mutation in oncogenes. The potential redifferentiating effect of inhibitors targeting oncogenic fusion genes is only suggested by a recent and unique publication using larotrectinib in a NTRK rearranged tumor. Patients finding. Selpercatinib a highly selective RET inhibitor, was recently approved by the FDA for the treatment of RET fusion-positive lung and thyroid cancers. We had the unprecedented opportunity to observe restoration of iodine-131 uptake after selpercatinib treatment for a non-radioiodine avid metastatic thyroid cancer with a RET/PTC3 fusion gene.

This finding of a redifferentiation effect with selpercatinib targeting a RET fusion gene, reinforces the proof of concept of this new therapeutic opportunity. Therefore, future clinical trials and treatment strategies must not forget to evaluate the redifferentiating effect of drugs targeting gene rearrangements. Furthermore, the combined approach with a targeted therapy and radioactive iodine may increase anti-tumor efficacy and minimize acquired resistance to RET inhibitors.
This finding of a redifferentiation effect with selpercatinib targeting a RET fusion gene, reinforces the proof of concept of this new therapeutic opportunity. Therefore, future clinical trials and treatment strategies must not forget to evaluate the redifferentiating effect of drugs targeting gene rearrangements. Furthermore, the combined approach with a targeted therapy and radioactive iodine may increase anti-tumor efficacy and minimize acquired resistance to RET inhibitors.
The current production and use of chlorinated paraffins (CPs) at



>


1


 million tons


/


y


likely exceeds the lifetime production of polychlorinated biphenyls (PCBs). These persistent organic pollutants (POPs) are a concern to human health.

The United Nations Environment Programme conducts global surveys of human milk samples from individual countries as a noninvasive method of investigating levels and trends in human exposures to POPs such as CPs. We measured CP concentrations and assessed their relation to other POPs in pooled samples collected during 2012-2019.

We analyzed 57 official nationwide pooled milk samples from 53 countries on five continents (Africa, Central/South America, Asia, Europe, and Australia/Oceania). CP concentrations were further characterized by subgroups and compared with concentrations of 19 other POPs, including PCBs and a variety of pesticides.

CPs were detected in pooled samples from all 53 countries, woward nonregulated medium-chain CPs (MCCPs) for these regions. The predominance of MCCPs in samples from many countries suggests a need for regulation and research on health effects. https//doi.org/10.1289/EHP7696.Oncolytic viruses are promising agents for cancer therapy, because they selectively infect and kill tumor cells, and also because they trigger immune responses that can boost anti-cancer immunity. Key to the latter process is the production of type I interferons (IFN-Is) that can turn non-inflamed "cold" tumors into "hot" ones. Besides this desired anti-cancer effect, IFN-Is are antiviral and successful oncolytic virotherapy thus relies on tightly controlled IFN-I levels. This requires a profound understanding of when and how tumor cells induce IFN-I in response to specific viruses. In this study, we uncovered two key factors that augment IFN-I production in transformed human myeloid cells infected with a tumor-selective reovirus. Viral replication and interferon-α/β receptor (IFNAR) signaling progressively reinforced the levels of IFN-I expressed by infected cells. Mechanistically, both augmented the activation of IRF3, a key transcription factor for IFNβ expression. Our findings imply that reovirus-permissive tumor cells themselves are a major source of IFN-I expression. As tumors can perturb the IFNAR pathway for their own survival, reovirus exposed IFNAR-unresponsive tumors may need additional therapeutic intervention to promote the secretion of sufficient IFN-I into the tumor microenvironment. Our increased understanding of the parameters that affect reovirus-induced IFN-I levels could aid in the design of tailored virus-based cancer therapies.The purpose of this study is to examine the effects of the COVID-19 pandemic on patients presenting with concussion at a specialty clinic. This study used a retrospective cohort design to compare participants (n = 3021) with a suspected concussion, including a Pandemic cohort (n = 1139; March 2020-February 2021) and a Pre-Pandemic cohort (n = 1882; March 2019-February 2020). Concussions and patient characteristics including age, sex, days since injury, and injury mechanism were extracted from an electronic health record. There were 39.5% (n = 743) fewer concussions in Pandemic. Pandemic presented to the clinic 25.8 days later (p  less then  0.001) and were 1.9 years older (p  less then  0.001) than Pre-Pandemic. Sport-related concussions decreased 59.6% overall for Pandemic. Pandemic was associated with proportional increases of concussions involving recreational activities (odds ratio [OR] = 6.11; p  less then  0.001), motor vehicle collisions (OR = 1.39; p  less then  0.001), and falls/assaults (OR = 1.33; p  less then  0.001). A total of 9.4% (107/1139) of all Pandemic concussion initial clinical visits were performed using telehealth (0% in Pre-Pandemic). Concussion visit volume to a sub-specialty clinic decreased by approximately 40% during the COVID-19 pandemic and patients presented to the clinic nearly 1 month later. The increase in telehealth highlights the potential to expand clinical care outreach during the current and future pandemics or similar restrictive time periods.Silicosis is an occupational disease caused by inhalation of silica dust, which is hallmarked by progressive pulmonary fibrosis associated with poor prognosis. Wnt/β-catenin signaling is implicated in the development of fibrosis and is a therapeutic target for fibrotic diseases. Previous clinical studies of patients with pneumoconioses including silicosis revealed an increased concentration of circulating WNT3A and DKK1 proteins and inflammatory cells in bronchoalveolar lavage compared to healthy subjects. The present study evaluated the effects of adenovirus-mediated transduction of Dickkopf-1 (Dkk1), a Wnt/β-catenin signaling inhibitor, on the development of pulmonary silicosis in mice. Consistent with previous human clinical studies, our experimental studies in mice demonstrated an aberrant Wnt/β-catenin signaling activity coinciding with increased Wnt3a and Dkk1 proteins and inflammation in lungs of silica-induced silicosis mice compared to controls. Intratracheal delivery of adenovirus expressing murine Dkk1 (AdDkk1) inhibited Wnt/β-catenin activity in mouse lungs. The Adenovirus-mediated Dkk1 gene transduction demonstrated potentials to prevent silicosis development and ameliorate silica-induced lung fibrogenesis in mice, companied with the reduced expression of epithelial-mesenchymal transition (EMT) markers and deposition of extracellular matrix (ECM) proteins compared to mice treated with "null" adenoviral vector. Mechanistically, AdDkk1 is able to attenuate the lung silicosis by inhibiting a silica-induced spike in TGF-β/Smad signaling. Additionally, the forced expression of Dkk1 suppressed silica-induced epithelial cell proliferation in polarized human bronchial epithelial cells. This study provides insight into the underlying role of Wnt/β-catenin signaling in promoting the pathogenesis of silicosis and is proof-of-concept that targeting Wnt/β-catenin signaling by Dkk1 gene transduction may be an alternative approach in prevention and treatment of silicosis lung disease.Background Case studies have linked synthetic cannabinoid (SC) use to suicide risk both during and following acute psychoactive effects. No study has explored whether a meaningful relationship exists between SC use and suicidal ideation, planning, and attempts within a generalizable sample. Aims This work attempted to determine whether SC use is significantly associated with suicidal thoughts, planning, or attempts and whether the association between SC use and suicide may be stronger in certain demographic groups. Method Cross-sectional self-report data from the Youth Risk Behavior Surveillance System were utilized. Logistic regression models were explored within a sample of 29,384 adolescents. Results A clear connection emerged between SC use and suicidal thoughts and attempts. SC use and suicide risk were strongly related within the lesbian, gay, and bisexual and African Americans populations, even after controlling for depressive symptoms. Limitations The study was cross-sectional and respondents may have underreported substance use or suicidal thoughts. Conclusion Whether SC use has an impact on suicidal ideation directly, indirectly, or if it is simply a co-occurring phenomenon, it may serve as a flag of enhanced risk. Physicians must remain cognizant of the SC-suicide risk connection, particularly among African American and/or lesbian, gay, or bisexual patients.Background People attending the emergency department (ED) for suicidal crisis are at significantly higher risk of taking their own lives in the week following discharge. Aims We aimed to evaluate the acceptability and feasibility of implementing a brief clinical aftercare intervention provided through Allied Health Brief Therapies (AHBTs) Clinics. Method Consecutive referrals (n = 149) to the clinics following assessment in the ED for suicidal crisis formed the study group. This article details participant engagement and retention, service provision, therapeutic alliance, and participant satisfaction with the program. Suicidal ideation and ED utilization 3 months pre-/postintervention were used to assess short-term impact. Results The study supports the feasibility of implementing a brief aftercare intervention for those presenting to the ED for suicidal crisis. High rates of therapeutic alliance and satisfaction with the clinic intervention were reported by participants. Impact assessments pointed to a significant reduction in both suicidal ideation and ED utilization following the intervention. Limitations A substantial number of participants had missing follow-up data. Given this and the absence of a control group, findings must be interpreted with caution. Rapamycin Conclusion The study supports the acceptability and feasibility of implementing AHBT Clinics as a potential adjunct in the aftercare of people in suicidal crisis.Background Bystanders can play a key role in preventing railway suicides by taking direct action or by raising an alarm. Aims The study investigated in this context (1) the prevalence of preventative actions by bystanders; (2) the relationship, if any, between first-hand preventions by bystanders and the degree of ambiguity around the imminence of danger; and (3) the nature of first-hand preventions by bystanders. Method Data were obtained from a security reporting database at Sydney Trains for 2011-2019 for accident and suicide-related incidents (N = 1,278). Results In 635 cases of suicide prevention, bystanders were identified as first responders in 11% of cases and as raising the alarm in 11% of cases. Bystanders as first responders intervened proportionally more where the ambiguity of danger is low (jumping) compared with high (sitting, standing, wandering). Of the 69 cases of bystander preventions, 77% involved physical interaction (e.g., holding back) and 49% involved more than one bystander. Limitations The data source could be biased because of incompleteness or nonstandard reporting.
Read More: https://www.selleckchem.com/products/Rapamycin.html